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An Open-label Extension Study To Evaluate Safety Of PF-06252616 In Boys With Duchenne Muscular Dystrophy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02907619
Recruitment Status : Terminated (Termination Date: 30Aug2018; Reason for termination: Lack of Efficacy)
First Posted : September 20, 2016
Results First Posted : November 25, 2019
Last Update Posted : November 25, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Masking: None (Open Label);   Primary Purpose: Treatment
Condition Duchenne Muscular Dystrophy
Intervention Biological: PF-06252616
Enrollment 59
Recruitment Details  
Pre-assignment Details Study B5161004 was an open-label extension (OLE) to study B5161002. The parent study B5161002 was a Phase 2, randomized, 2-period, blinded, placebo controlled study to evaluate the safety, efficacy, PK and PD of domagrozumab administered to ambulatory boys diagnosed with DMD.
Arm/Group Title Sequence 1 Sequence 2 Sequence 3
Hide Arm/Group Description In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study. In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study. In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
Period Title: Overall Study
Started 19 20 20
Received Treatment 19 20 20
Completed 0 0 0
Not Completed 19 20 20
Reason Not Completed
Study terminated by sponsor             18             18             19
Death             0             0             1
Withdrawal by Subject             1             1             0
Other             0             1             0
Arm/Group Title Sequence 1 Sequence 2 Sequence 3 Total
Hide Arm/Group Description In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study. In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study. In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study. Total of all reporting groups
Overall Number of Baseline Participants 19 20 20 59
Hide Baseline Analysis Population Description
Baseline analysis population included all participants who received at least 1 dose of study treatment in this study B5161004.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 20 participants 20 participants 59 participants
<=18 years
19
 100.0%
20
 100.0%
20
 100.0%
59
 100.0%
Between 18 and 65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 19 participants 20 participants 20 participants 59 participants
9.1  (1.0) 10.2  (0.9) 10.4  (1.1) 9.9  (1.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 20 participants 20 participants 59 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Male
19
 100.0%
20
 100.0%
20
 100.0%
59
 100.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 20 participants 20 participants 59 participants
White
18
  94.7%
17
  85.0%
18
  90.0%
53
  89.8%
Asian
1
   5.3%
2
  10.0%
2
  10.0%
5
   8.5%
Other
0
   0.0%
1
   5.0%
0
   0.0%
1
   1.7%
1.Primary Outcome
Title Number of Participants With Dose Reduced or Temporary Discontinuation Due to AEs
Hide Description An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment or usage. Treatment-related AEs were determined by the investigator. The number of participants with dose reduced or temporary discontinuation due to both all-causality and treatment-related AEs are presented below.
Time Frame 2 Years
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all participants who had received at least 1 dose of study medication in current study B5161004.
Arm/Group Title Sequence 1 Sequence 2 Sequence 3 Total
Hide Arm/Group Description:
In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
Sum of all participants in the study B5161004
Overall Number of Participants Analyzed 19 20 20 59
Measure Type: Count of Participants
Unit of Measure: Participants
Due to All-causality AEs
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Due to Treatment-related AEs
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2.Primary Outcome
Title Number of Participants With Severe Treatment-Emergent Adverse Events (TEAEs)
Hide Description An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment or usage. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Severe TEAEs were TEAEs that interfered significantly with participants' usual function. Treatment-related TEAEs were determined by the investigator. The number of participants with severe all-causality and treatment-related TEAEs are presented below.
Time Frame 2 Years
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all participants who had received at least 1 dose of study medication in current study B5161004.
Arm/Group Title Sequence 1 Sequence 2 Sequence 3 Total
Hide Arm/Group Description:
In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
Sum of all participants in the study B5161004
Overall Number of Participants Analyzed 19 20 20 59
Measure Type: Count of Participants
Unit of Measure: Participants
All-Causality TEAEs
3
  15.8%
0
   0.0%
1
   5.0%
4
   6.8%
Treatment-Related TEAEs
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
3.Primary Outcome
Title Number of Participants Who Discontinued From the Study Due to TEAEs
Hide Description An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment or usage. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Treatment-related TEAEs were determined by the investigator. The number of participants who discontinued from the study due to both all-causality and treatment-related TEAEs are presented below.
Time Frame 2 Years
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all participants who had received at least 1 dose of study medication in current study B5161004.
Arm/Group Title Sequence 1 Sequence 2 Sequence 3 Total
Hide Arm/Group Description:
In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
Sum of all participants in the study B5161004
Overall Number of Participants Analyzed 19 20 20 59
Measure Type: Count of Participants
Unit of Measure: Participants
Due to All-causality AEs
0
   0.0%
0
   0.0%
1
   5.0%
1
   1.7%
Due to Treatment-related AEs
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
4.Primary Outcome
Title Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hematology
Hide Description

Hematology evaluation included: hemoglobin, hematocrit, red blood cell (RBC) count, platelets, RBC morphology, white blood cell (WBC) count, absolute lymphocytes, absolute atypical lymphocytes, absolute total neutrophils, absolute total neutrophils count, absolute band cells, absolute basophils, absolute eosinophils and absolute monocytes.

Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004.

(ULN=Upper Limit of Normal; LLN=Lower Limit of Normal).

Time Frame 2 Years
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population included all participants who had received at least 1 dose of study medication in current study B5161004. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
Arm/Group Title Sequence 1 Sequence 2 Sequence 3 Total
Hide Arm/Group Description:
In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
Sum of all participants in the study B5161004
Overall Number of Participants Analyzed 19 20 20 59
Measure Type: Count of Participants
Unit of Measure: Participants
Hemoglobin <0.8 × LLN Number Analyzed 19 participants 20 participants 20 participants 59 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Hematocrit <0.8 × LLN Number Analyzed 19 participants 20 participants 20 participants 59 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
RBC count <0.8 × LLN Number Analyzed 19 participants 20 participants 20 participants 59 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Platelets <0.5 × LLN Number Analyzed 19 participants 20 participants 20 participants 59 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Platelets >1.75 × ULN Number Analyzed 19 participants 20 participants 20 participants 59 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
RBC Morphology >0 Number Analyzed 19 participants 20 participants 20 participants 59 participants
0
   0.0%
1
   5.0%
0
   0.0%
1
   1.7%
WBC count <0.6 × LLN Number Analyzed 19 participants 20 participants 20 participants 59 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
WBC count >1.5 × ULN Number Analyzed 19 participants 20 participants 20 participants 59 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Absolute Lymphocytes <0.8 × LLN Number Analyzed 19 participants 20 participants 20 participants 59 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Absolute lymphocytes >1.2 × ULN Number Analyzed 19 participants 20 participants 20 participants 59 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Absolute atypical lymphocytes >0 Number Analyzed 1 participants 0 participants 0 participants 1 participants
1
 100.0%
1
 100.0%
Absolute total neutrophils <0.8 × LLN Number Analyzed 19 participants 20 participants 20 participants 59 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Absolute total neutrophils >1.2 × ULN Number Analyzed 19 participants 20 participants 20 participants 59 participants
3
  15.8%
1
   5.0%
2
  10.0%
6
  10.2%
Absolute total neutrophil count <1.35 × 10^3/mcL Number Analyzed 19 participants 20 participants 20 participants 59 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Absolute total neutrophil count >8.15 × 10^3/mcL Number Analyzed 19 participants 20 participants 20 participants 59 participants
6
  31.6%
1
   5.0%
5
  25.0%
12
  20.3%
Absolute band cells >0.27 × 10^3/mcL Number Analyzed 1 participants 0 participants 0 participants 1 participants
0
   0.0%
0
   0.0%
Absolute basophils >1.2 × ULN Number Analyzed 19 participants 20 participants 20 participants 59 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Absolute eosinophils >1.2 × ULN Number Analyzed 19 participants 20 participants 20 participants 59 participants
1
   5.3%
0
   0.0%
1
   5.0%
2
   3.4%
Absolute monocytes >1.2 × ULN Number Analyzed 19 participants 20 participants 20 participants 59 participants
1
   5.3%
0
   0.0%
1
   5.0%
2
   3.4%
5.Primary Outcome
Title Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Coagulation
Hide Description

Coagulation evaluation included activated partial thromboplastin time (aPTT) and prothrombin time (PT).

(ULN=Upper Limit of Normal). Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004.

Time Frame 2 Years
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population included all participants who had received at least 1 dose of study medication in current study B5161004.
Arm/Group Title Sequence 1 Sequence 2 Sequence 3 Total
Hide Arm/Group Description:
In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
Sum of all participants in the study B5161004
Overall Number of Participants Analyzed 19 20 20 59
Measure Type: Count of Participants
Unit of Measure: Participants
aPTT >1.1 x ULN
0
   0.0%
0
   0.0%
1
   5.0%
1
   1.7%
PT >1.1 x ULN
1
   5.3%
0
   0.0%
1
   5.0%
2
   3.4%
6.Primary Outcome
Title Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Liver Function
Hide Description

Liver function evaluation included: total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), alkaline phosphatase, total protein, albumin and glutamate dehydrogenase.

Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004.

(LLN=Lower Limit of Normal; ULN=Upper Limit of Normal).

Time Frame 2 Years
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population included all participants who had received at least 1 dose of study medication in current study B5161004.
Arm/Group Title Sequence 1 Sequence 2 Sequence 3 Total
Hide Arm/Group Description:
In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
Sum of all participants in the study B5161004
Overall Number of Participants Analyzed 19 20 20 59
Measure Type: Count of Participants
Unit of Measure: Participants
Total Bilirubin >1.5 x ULN
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
AST >3.0 x ULN
16
  84.2%
16
  80.0%
15
  75.0%
47
  79.7%
ALT >3.0 x ULN
19
 100.0%
18
  90.0%
19
  95.0%
56
  94.9%
GGT >3.0 x ULN
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Alkaline Phosphatase >3.0 x ULN
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Total Protein <0.8 x LLN
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Total Protein >1.2 x ULN
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Albumin <0.8 x LLN
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Albumin >1.2 x ULN
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Glutamate Dehydrogenase >1.0 x ULN
0
   0.0%
0
   0.0%
1
   5.0%
1
   1.7%
7.Primary Outcome
Title Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Renal Function
Hide Description

Renal function evaluation included: blood urea nitrogen (BUN), creatinine and uric acid.

Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. (ULN=Upper Limit of Normal).

Time Frame 2 Years
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population included all participants who had received at least 1 dose of study medication in current study B5161004.
Arm/Group Title Sequence 1 Sequence 2 Sequence 3 Total
Hide Arm/Group Description:
In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
Sum of all participants in the study B5161004
Overall Number of Participants Analyzed 19 20 20 59
Measure Type: Count of Participants
Unit of Measure: Participants
Blood Urea Nitrogen (BUN) >1.3 x ULN
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Creatinine >1.3 x ULN
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Uric Acid >1.2 x ULN
1
   5.3%
0
   0.0%
0
   0.0%
1
   1.7%
8.Primary Outcome
Title Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Electrolytes
Hide Description

Electrolytes evaluation included: sodium, potassium, chloride, calcium, phosphate and bicarbonate.

Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004.

(LLN=Lower Limit of Normal, ULN=Upper Limit of Normal).

Time Frame 2 Years
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population included all participants who had received at least 1 dose of study medication in current study B5161004.
Arm/Group Title Sequence 1 Sequence 2 Sequence 3 Total
Hide Arm/Group Description:
In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
Sum of all participants in the study B5161004
Overall Number of Participants Analyzed 19 20 20 59
Measure Type: Count of Participants
Unit of Measure: Participants
Sodium <0.95 x LLN
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Sodium >1.05 x ULN
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Potassium <0.9 x LLN
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Potassium >1.1 x ULN
1
   5.3%
0
   0.0%
0
   0.0%
1
   1.7%
Chloride <0.9 x LLN
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Chloride >1.1 x ULN
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Calcium <0.9 x LLN
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Calcium >1.1 x ULN
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Phosphate <0.8 x LLN
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Phosphate >1.2 x ULN
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Bicarbonate (venous) <0.9 x LLN
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Bicarbonate (venous) >1.1 x ULN
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
9.Primary Outcome
Title Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hormones
Hide Description

Hormone evaluations included free thyroxine (T4), thyroid stimulating hormone (TSH), lutenizing hormone (LH), follicle stimulating hormone (FSH), and androstenedione. Numbers of participants with abnormalities of LH, FSH and androstenedione were reported in different age groups.

Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004.

(LLN=Lower Limit of Normal, ULN=Upper Limit of Normal).

Time Frame 2 Years
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population included all participants who had received at least 1 dose of study medication in current study B5161004. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
Arm/Group Title Sequence 1 Sequence 2 Sequence 3 Total
Hide Arm/Group Description:
In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
Sum of all participants in the study B5161004
Overall Number of Participants Analyzed 19 20 20 59
Measure Type: Count of Participants
Unit of Measure: Participants
T4 (free) <0.8 x LLN Number Analyzed 18 participants 18 participants 17 participants 53 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
T4 (free) >1.2 x ULN Number Analyzed 18 participants 18 participants 17 participants 53 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
TSH <0.8 x LLN Number Analyzed 18 participants 18 participants 17 participants 53 participants
0
   0.0%
1
   5.6%
0
   0.0%
1
   1.9%
TSH >1.2 x ULN Number Analyzed 18 participants 18 participants 17 participants 53 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
LH (7years - <9 years) <0.3mIU/mL Number Analyzed 2 participants 0 participants 0 participants 2 participants
0
   0.0%
0
   0.0%
LH(7years - <9 years) >2.8mIU/mL Number Analyzed 2 participants 0 participants 0 participants 2 participants
0
   0.0%
0
   0.0%
LH (9years - <11 years) <0.3mIU/mL Number Analyzed 13 participants 5 participants 4 participants 22 participants
8
  61.5%
5
 100.0%
3
  75.0%
16
  72.7%
LH (9years - <11 years) >2.8mIU/mL Number Analyzed 13 participants 5 participants 4 participants 22 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
LH (11years - <12 years) <0.3mIU/mL Number Analyzed 3 participants 6 participants 2 participants 11 participants
2
  66.7%
3
  50.0%
2
 100.0%
7
  63.6%
LH (11years - <12 years) >1.8mIU/mL Number Analyzed 3 participants 6 participants 2 participants 11 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
LH(12years - <13 years) <0.3 mIU/mL Number Analyzed 1 participants 8 participants 11 participants 20 participants
0
   0.0%
5
  62.5%
8
  72.7%
13
  65.0%
LH(12years - <13 years) >4.0mIU/mL Number Analyzed 1 participants 8 participants 11 participants 20 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
LH(13years - <14 years) <0.3mIU/mL Number Analyzed 1 participants 1 participants 1 participants 3 participants
1
 100.0%
0
   0.0%
1
 100.0%
2
  66.7%
LH(13years - <14 years) >6.0mIU/mL Number Analyzed 1 participants 1 participants 1 participants 3 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
FSH(7years - <9 years) >4.10mIU/mL Number Analyzed 2 participants 0 participants 0 participants 2 participants
0
   0.0%
0
   0.0%
FSH (9years - <11 years) >4.50mIU/mL Number Analyzed 13 participants 5 participants 4 participants 22 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
FSH (11years - <12 years) <0.40mIU/mL Number Analyzed 3 participants 6 participants 2 participants 11 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
FSH (11years - <12 years) >8.90mIU/mL Number Analyzed 3 participants 6 participants 2 participants 11 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
FSH (12years - <13 years) <0.50mIU/mL Number Analyzed 1 participants 8 participants 11 participants 20 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
FSH (12years - <13 years) >10.50mIU/mL Number Analyzed 1 participants 8 participants 11 participants 20 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
FSH (13years - <14 years) <0.70mIU/mL Number Analyzed 1 participants 1 participants 1 participants 3 participants
1
 100.0%
0
   0.0%
1
 100.0%
2
  66.7%
FSH (13 years - <14 years) >10.80mIU/mL Number Analyzed 1 participants 1 participants 1 participants 3 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Androstenedione (7 - <10years) <3 ng/dL Number Analyzed 6 participants 2 participants 4 participants 12 participants
0
   0.0%
0
   0.0%
2
  50.0%
2
  16.7%
Androstenedione(7 - <10 years) >31 ng/dL Number Analyzed 6 participants 2 participants 4 participants 12 participants
1
  16.7%
1
  50.0%
0
   0.0%
2
  16.7%
Androstenedione (10 - <12years) <7 ng/dL Number Analyzed 12 participants 9 participants 2 participants 23 participants
5
  41.7%
3
  33.3%
1
  50.0%
9
  39.1%
Androstenedione (10-<12years) >41 ng/dL Number Analyzed 12 participants 9 participants 2 participants 23 participants
1
   8.3%
0
   0.0%
0
   0.0%
1
   4.3%
Androstenedione (12 - <14years) <11 ng/dL Number Analyzed 1 participants 8 participants 11 participants 20 participants
1
 100.0%
4
  50.0%
6
  54.5%
11
  55.0%
Androstenedione (12 - <14years) >64 ng/dL Number Analyzed 1 participants 8 participants 11 participants 20 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
10.Primary Outcome
Title Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Clinical Chemistry
Hide Description

Clinical chemistry evaluation included glucose, creatine kinase (CK), troponin I, amylase, iron binding capacity, unsaturated iron binding capacity, transferrin saturation, iron and ferritin. Number of participants with iron abnormalities was reported in different age groups.

Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004.

(LLN=Lower Limit of Normal, ULN=Upper Limit of Normal).

Time Frame 2 Years
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population included all participants who had received at least 1 dose of study medication in current study B5161004. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
Arm/Group Title Sequence 1 Sequence 2 Sequence 3 Total
Hide Arm/Group Description:
In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
Sum of all participants in the study B5161004
Overall Number of Participants Analyzed 19 20 20 59
Measure Type: Count of Participants
Unit of Measure: Participants
Glucose <0.6 x LLN Number Analyzed 19 participants 20 participants 20 participants 59 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Glucose >1.5 x ULN Number Analyzed 19 participants 20 participants 20 participants 59 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
CK >2.0 x ULN Number Analyzed 19 participants 20 participants 20 participants 59 participants
19
 100.0%
20
 100.0%
20
 100.0%
59
 100.0%
Troponin I >3.0 x ULN Number Analyzed 19 participants 18 participants 17 participants 54 participants
4
  21.1%
4
  22.2%
1
   5.9%
9
  16.7%
Amylase > 1.5 x ULN Number Analyzed 19 participants 20 participants 20 participants 59 participants
0
   0.0%
0
   0.0%
1
   5.0%
1
   1.7%
Iron Binding Capacity <37.6 mcg/dL Number Analyzed 19 participants 20 participants 20 participants 59 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unsaturated Iron Binding Capacity <130 mcg/dL Number Analyzed 19 participants 20 participants 20 participants 59 participants
3
  15.8%
4
  20.0%
3
  15.0%
10
  16.9%
Unsaturated Iron Binding Capacity >375 mcg/dL Number Analyzed 19 participants 20 participants 20 participants 59 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Transferrin Saturation < 20% Number Analyzed 19 participants 20 participants 20 participants 59 participants
0
   0.0%
3
  15.0%
2
  10.0%
5
   8.5%
Transferrin Saturation > 50% Number Analyzed 19 participants 20 participants 20 participants 59 participants
7
  36.8%
4
  20.0%
6
  30.0%
17
  28.8%
Iron 1Y<=Age<11Y <50 Number Analyzed 17 participants 8 participants 6 participants 31 participants
0
   0.0%
0
   0.0%
1
  16.7%
1
   3.2%
Iron 1Y<=Age<11Y >120 Number Analyzed 17 participants 8 participants 6 participants 31 participants
12
  70.6%
2
  25.0%
2
  33.3%
16
  51.6%
Iron 11Y<=Age<18Y <50 Number Analyzed 4 participants 15 participants 15 participants 34 participants
0
   0.0%
3
  20.0%
0
   0.0%
3
   8.8%
Iron 11Y<=Age<18Y >170 Number Analyzed 4 participants 15 participants 15 participants 34 participants
0
   0.0%
1
   6.7%
1
   6.7%
2
   5.9%
Ferritin <15 ng/mL Number Analyzed 19 participants 20 participants 20 participants 59 participants
4
  21.1%
6
  30.0%
5
  25.0%
15
  25.4%
Ferritin >140 ng/mL Number Analyzed 19 participants 20 participants 20 participants 59 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
11.Primary Outcome
Title Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Urinalysis
Hide Description

Urinalysis Microscopy included: urine red blood cell (RBC), urine white blood cell (WBC), urine uric acid crystals, urine calcium oxalate crystals, urine amorphous crystals, urine bacteria, urine microscopic exam.

Urinalysis Dipstick included: urine pH, urine glucose, urine ketones, urine protein, urine blood/hemoglobin, urine nitrite, urine leukocyte esterase.

Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004.

Time Frame 2 Years
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population included all participants who had received at least 1 dose of study medication in current study B5161004. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
Arm/Group Title Sequence 1 Sequence 2 Sequence 3 Total
Hide Arm/Group Description:
In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
Sum of all participants in the study B5161004
Overall Number of Participants Analyzed 19 20 20 59
Measure Type: Count of Participants
Unit of Measure: Participants
Microscopy - Urine RBC >=20 Number Analyzed 2 participants 3 participants 1 participants 6 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Microscopy - Urine WBC >=20 Number Analyzed 6 participants 8 participants 6 participants 20 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Microscopy-Urine Uric Acid Crystals -Present Number Analyzed 1 participants 0 participants 0 participants 1 participants
1
 100.0%
1
 100.0%
Microscopy-Urine Calcium Oxalate Crystals -Present Number Analyzed 4 participants 7 participants 4 participants 15 participants
4
 100.0%
7
 100.0%
4
 100.0%
15
 100.0%
Microscopy-Urine Amorphous Crystals -Present Number Analyzed 3 participants 3 participants 2 participants 8 participants
3
 100.0%
3
 100.0%
2
 100.0%
8
 100.0%
Microscopy - Urine Bacteria >20 Number Analyzed 1 participants 1 participants 0 participants 2 participants
0
   0.0%
0
   0.0%
0
   0.0%
Microscopy-Urine Microscopic Exam -Positive Number Analyzed 9 participants 11 participants 8 participants 28 participants
8
  88.9%
11
 100.0%
7
  87.5%
26
  92.9%
Dipstick - Urine pH <4.5 Number Analyzed 19 participants 20 participants 20 participants 59 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Dipstick - Urine pH >8 Number Analyzed 19 participants 20 participants 20 participants 59 participants
0
   0.0%
1
   5.0%
0
   0.0%
1
   1.7%
Dipstick - urine glucose >=1 Number Analyzed 19 participants 20 participants 20 participants 59 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Dipstick - urine ketones >=1 Number Analyzed 19 participants 20 participants 20 participants 59 participants
0
   0.0%
1
   5.0%
1
   5.0%
2
   3.4%
Dipstick - urine protein >=1 Number Analyzed 19 participants 20 participants 20 participants 59 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Dipstick - urine blood/hemoglobin >=1 Number Analyzed 19 participants 20 participants 20 participants 59 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Dipstick - Urine nitrite >=1 Number Analyzed 19 participants 20 participants 20 participants 59 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Dipstick - Urine Leukocyte Esterase >=1 Number Analyzed 19 participants 20 participants 20 participants 59 participants
0
   0.0%
1
   5.0%
0
   0.0%
1
   1.7%
12.Primary Outcome
Title Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Fecal Blood
Hide Description

Number of participants with blood detected in fecal samples is presented. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004.

(ULN=Upper Limit of Normal).

Time Frame 2 Years
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population included all participants who had received at least 1 dose of study medication in current study B5161004 and who were evaluable for this outcome measure.
Arm/Group Title Sequence 1 Sequence 2 Sequence 3 Total
Hide Arm/Group Description:
In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
Sum of all participants in the study B5161004
Overall Number of Participants Analyzed 19 17 17 53
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
13.Primary Outcome
Title Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline
Hide Description

Participants were asked to fast for at least 8 hours prior to collection of blood to evaluate serum iron, serum ferritin and % transferrin saturation. The unit of iron was mcg/dL; the unit of ferritin was ng/mL; the unit of %transferrin saturation was %.

Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.

Time Frame Baseline, Weeks 13, 25, 37, 49, 61, 73 and 85.
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population included all participants who had received at least 1 dose of study medication in current study B5161004. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
Arm/Group Title Sequence 1 Sequence 2 Sequence 3 Total
Hide Arm/Group Description:
In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
Sum of all participants in the study B5161004
Overall Number of Participants Analyzed 19 20 20 59
Measure Type: Count of Participants
Unit of Measure: Participants
Iron - Baseline: <120 Number Analyzed 19 participants 20 participants 20 participants 59 participants
13
  68.4%
18
  90.0%
10
  50.0%
41
  69.5%
Iron - Baseline: 120 - <144 Number Analyzed 19 participants 20 participants 20 participants 59 participants
3
  15.8%
2
  10.0%
6
  30.0%
11
  18.6%
Iron - Baseline: 144 - <200 Number Analyzed 19 participants 20 participants 20 participants 59 participants
3
  15.8%
0
   0.0%
4
  20.0%
7
  11.9%
Iron - Baseline: >=200 Number Analyzed 19 participants 20 participants 20 participants 59 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Iron - Week 13: <120 Number Analyzed 15 participants 16 participants 17 participants 48 participants
10
  66.7%
15
  93.8%
9
  52.9%
34
  70.8%
Iron - Week 13: 120 - <144 Number Analyzed 15 participants 16 participants 17 participants 48 participants
3
  20.0%
0
   0.0%
7
  41.2%
10
  20.8%
Iron - Week 13: 144 - <200 Number Analyzed 15 participants 16 participants 17 participants 48 participants
2
  13.3%
1
   6.3%
1
   5.9%
4
   8.3%
Iron - Week 13: >=200 Number Analyzed 15 participants 16 participants 17 participants 48 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Iron - Week 25: <120 Number Analyzed 12 participants 12 participants 13 participants 37 participants
8
  66.7%
10
  83.3%
8
  61.5%
26
  70.3%
Iron - Week 25: 120 - <144 Number Analyzed 12 participants 12 participants 13 participants 37 participants
3
  25.0%
0
   0.0%
4
  30.8%
7
  18.9%
Iron - Week 25: 144 - <200 Number Analyzed 12 participants 12 participants 13 participants 37 participants
1
   8.3%
2
  16.7%
1
   7.7%
4
  10.8%
Iron - Week 25: >=200 Number Analyzed 12 participants 12 participants 13 participants 37 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Iron-Week 37: <120 Number Analyzed 8 participants 9 participants 12 participants 29 participants
5
  62.5%
6
  66.7%
10
  83.3%
21
  72.4%
Iron-Week 37: 120 - <144 Number Analyzed 8 participants 9 participants 12 participants 29 participants
1
  12.5%
3
  33.3%
2
  16.7%
6
  20.7%
Iron-Week 37: 144 - <200 Number Analyzed 8 participants 9 participants 12 participants 29 participants
2
  25.0%
0
   0.0%
0
   0.0%
2
   6.9%
Iron-Week 37: >=200 Number Analyzed 8 participants 9 participants 12 participants 29 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Iron-Week 49: <120 Number Analyzed 7 participants 6 participants 8 participants 21 participants
6
  85.7%
3
  50.0%
6
  75.0%
15
  71.4%
Iron-Week 49: 120 - <144 Number Analyzed 7 participants 6 participants 8 participants 21 participants
1
  14.3%
0
   0.0%
1
  12.5%
2
   9.5%
Iron-Week 49: 144 - <200 Number Analyzed 7 participants 6 participants 8 participants 21 participants
0
   0.0%
3
  50.0%
1
  12.5%
4
  19.0%
Iron-Week 49: >=200 Number Analyzed 7 participants 6 participants 8 participants 21 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Iron-Week 61: <120 Number Analyzed 3 participants 4 participants 3 participants 10 participants
1
  33.3%
2
  50.0%
2
  66.7%
5
  50.0%
Iron-Week 61: 120 - <144 Number Analyzed 3 participants 4 participants 3 participants 10 participants
1
  33.3%
1
  25.0%
1
  33.3%
3
  30.0%
Iron-Week 61: 144 - <200 Number Analyzed 3 participants 4 participants 3 participants 10 participants
1
  33.3%
1
  25.0%
0
   0.0%
2
  20.0%
Iron-Week 61: >=200 Number Analyzed 3 participants 4 participants 3 participants 10 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Iron-Week 73: <120 Number Analyzed 2 participants 2 participants 2 participants 6 participants
1
  50.0%
1
  50.0%
2
 100.0%
4
  66.7%
Iron-Week 73: 120 - <144 Number Analyzed 2 participants 2 participants 2 participants 6 participants
1
  50.0%
0
   0.0%
0
   0.0%
1
  16.7%
Iron-Week 73: 144 - <200 Number Analyzed 2 participants 2 participants 2 participants 6 participants
0
   0.0%
1
  50.0%
0
   0.0%
1
  16.7%
Iron-Week 73: >=200 Number Analyzed 2 participants 2 participants 2 participants 6 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Iron-Week 85: <120 Number Analyzed 0 participants 1 participants 1 participants 2 participants
0
1
 100.0%
1
 100.0%
2
 100.0%
Iron-Week 85: 120 - <144 Number Analyzed 0 participants 1 participants 1 participants 2 participants
0
0
   0.0%
0
   0.0%
0
   0.0%
Iron-Week 85: 144 - <200 Number Analyzed 0 participants 1 participants 1 participants 2 participants
0
0
   0.0%
0
   0.0%
0
   0.0%
Iron-Week 85: >=200 Number Analyzed 0 participants 1 participants 1 participants 2 participants
0
0
   0.0%
0
   0.0%
0
   0.0%
Ferritin-Baseline: <140 Number Analyzed 19 participants 20 participants 20 participants 59 participants
19
 100.0%
20
 100.0%
20
 100.0%
59
 100.0%
Ferritin-Baseline: >=140 Number Analyzed 19 participants 20 participants 20 participants 59 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Ferritin-Week 13: <140 Number Analyzed 14 participants 17 participants 16 participants 47 participants
14
 100.0%
17
 100.0%
16
 100.0%
47
 100.0%
Ferritin-Week 13: >=140 Number Analyzed 14 participants 17 participants 16 participants 47 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Ferritin-Week 25: <140 Number Analyzed 12 participants 12 participants 13 participants 37 participants
12
 100.0%
12
 100.0%
13
 100.0%
37
 100.0%
Ferritin-Week 25: >=140 Number Analyzed 12 participants 12 participants 13 participants 37 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Ferritin-Week 37: <140 Number Analyzed 7 participants 9 participants 12 participants 28 participants
7
 100.0%
9
 100.0%
12
 100.0%
28
 100.0%
Ferritin-Week 37: >=140 Number Analyzed 7 participants 9 participants 12 participants 28 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Ferritin-Week 49: <140 Number Analyzed 7 participants 6 participants 8 participants 21 participants
7
 100.0%
6
 100.0%
8
 100.0%
21
 100.0%
Ferritin-Week 49: >=140 Number Analyzed 7 participants 6 participants 8 participants 21 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Ferritin-Week 61: <140 Number Analyzed 2 participants 4 participants 3 participants 9 participants
2
 100.0%
4
 100.0%
3
 100.0%
9
 100.0%
Ferritin-Week 61: >=140 Number Analyzed 2 participants 4 participants 3 participants 9 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Ferritin-Week 73: <140 Number Analyzed 2 participants 2 participants 2 participants 6 participants
2
 100.0%
2
 100.0%
2
 100.0%
6
 100.0%
Ferritin-Week 73: >=140 Number Analyzed 2 participants 2 participants 2 participants 6 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Ferritin-Week 85: <140 Number Analyzed 0 participants 1 participants 1 participants 2 participants
0
1
 100.0%
1
 100.0%
2
 100.0%
Ferritin-Week 85: >=140 Number Analyzed 0 participants 1 participants 1 participants 2 participants
0
0
   0.0%
0
   0.0%
0
   0.0%
%Transferrin Saturation - Baseline: <45 Number Analyzed 18 participants 20 participants 20 participants 58 participants
15
  83.3%
20
 100.0%
18
  90.0%
53
  91.4%
%Transferrin Saturation Baseline: 45 - <50 Number Analyzed 18 participants 20 participants 20 participants 58 participants
3
  16.7%
0
   0.0%
1
   5.0%
4
   6.9%
%Transferrin Saturation Baseline: 50 - <69 Number Analyzed 18 participants 20 participants 20 participants 58 participants
0
   0.0%
0
   0.0%
1
   5.0%
1
   1.7%
%Transferrin Saturation Baseline: >=69 Number Analyzed 18 participants 20 participants 20 participants 58 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
%Transferrin Saturation Week 13: <45 Number Analyzed 15 participants 16 participants 16 participants 47 participants
12
  80.0%
15
  93.8%
13
  81.3%
40
  85.1%
%Transferrin Saturation Week 13: 45 - <50 Number Analyzed 15 participants 16 participants 16 participants 47 participants
1
   6.7%
0
   0.0%
1
   6.3%
2
   4.3%
%Transferrin Saturation Week 13: 50 - <69 Number Analyzed 15 participants 16 participants 16 participants 47 participants
2
  13.3%
1
   6.3%
2
  12.5%
5
  10.6%
%Transferrin Saturation Week 13: >=69 Number Analyzed 15 participants 16 participants 16 participants 47 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
%Transferrin Saturation Week 25: <45 Number Analyzed 10 participants 12 participants 13 participants 35 participants
9
  90.0%
10
  83.3%
9
  69.2%
28
  80.0%
%Transferrin Saturation Week 25: 45 - <50 Number Analyzed 10 participants 12 participants 13 participants 35 participants
0
   0.0%
1
   8.3%
2
  15.4%
3
   8.6%
%Transferrin Saturation Week 25: 50 - <69 Number Analyzed 10 participants 12 participants 13 participants 35 participants
1
  10.0%
1
   8.3%
2
  15.4%
4
  11.4%
%Transferrin Saturation Week 25: >=69 Number Analyzed 10 participants 12 participants 13 participants 35 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
%Transferrin Saturation Week 37: <45 Number Analyzed 6 participants 7 participants 12 participants 25 participants
4
  66.7%
6
  85.7%
11
  91.7%
21
  84.0%
%Transferrin Saturation Week 37: 45 - <50 Number Analyzed 6 participants 7 participants 12 participants 25 participants
1
  16.7%
0
   0.0%
0
   0.0%
1
   4.0%
%Transferrin Saturation Week 37: 50 - <69 Number Analyzed 6 participants 7 participants 12 participants 25 participants
1
  16.7%
1
  14.3%
1
   8.3%
3
  12.0%
%Transferrin Saturation Week 37: >=69 Number Analyzed 6 participants 7 participants 12 participants 25 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
%Transferrin Saturation Week 49: <45 Number Analyzed 7 participants 6 participants 8 participants 21 participants
6
  85.7%
4
  66.7%
6
  75.0%
16
  76.2%
%Transferrin Saturation Week 49: 45 - <50 Number Analyzed 7 participants 6 participants 8 participants 21 participants
0
   0.0%
0
   0.0%
1
  12.5%
1
   4.8%
%Transferrin Saturation Week 49: 50 - <69 Number Analyzed 7 participants 6 participants 8 participants 21 participants
1
  14.3%
2
  33.3%
1
  12.5%
4
  19.0%
%Transferrin Saturation Week 49: >=69 Number Analyzed 7 participants 6 participants 8 participants 21 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
%Transferrin Saturation Week 61: <45 Number Analyzed 1 participants 3 participants 3 participants 7 participants
1
 100.0%
2
  66.7%
3
 100.0%
6
  85.7%
%Transferrin Saturation Week 61: 45 - <50 Number Analyzed 1 participants 3 participants 3 participants 7 participants
0
   0.0%
1
  33.3%
0
   0.0%
1
  14.3%
%Transferrin Saturation Week 61: 50 - <69 Number Analyzed 1 participants 3 participants 3 participants 7 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
%Transferrin Saturation Week 61: >=69 Number Analyzed 1 participants 3 participants 3 participants 7 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
%Transferrin Saturation Week 73: <45 Number Analyzed 2 participants 2 participants 2 participants 6 participants
2
 100.0%
1
  50.0%
2
 100.0%
5
  83.3%
%Transferrin Saturation Week 73: 45 - <50 Number Analyzed 2 participants 2 participants 2 participants 6 participants
0
   0.0%
1
  50.0%
0
   0.0%
1
  16.7%
%Transferrin Saturation Week 73: 50 - <69 Number Analyzed 2 participants 2 participants 2 participants 6 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
%Transferrin Saturation Week 73: >=69 Number Analyzed 2 participants 2 participants 2 participants 6 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
%Transferrin Saturation Week 85: <45 Number Analyzed 0 participants 1 participants 1 participants 2 participants
0
1
 100.0%
1
 100.0%
2
 100.0%
%Transferrin Saturation Week 85: 45 - <50 Number Analyzed 0 participants 1 participants 1 participants 2 participants
0
0
   0.0%
0
   0.0%
0
   0.0%
%Transferrin Saturation Week 85: 50 - <69 Number Analyzed 0 participants 1 participants 1 participants 2 participants
0
0
   0.0%
0
   0.0%
0
   0.0%
%Transferrin Saturation Week 85: >=69 Number Analyzed 0 participants 1 participants 1 participants 2 participants
0
0
   0.0%
0
   0.0%
0
   0.0%
14.Primary Outcome
Title Number of Participants With Significant Results of Physical Examinations Including Nose and Throat Mucosal Examinations
Hide Description Physical examinations were conducted by a physician, trained physician's assistant, or nurse practitioner as acceptable according to local regulation. A targeted nose and throat mucosal exam was performed to monitor for any signs of mucosal telangiectasias. The clinically significant physical examination results were determined by the investigator.
Time Frame 2 Years
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population included all participants who had received at least 1 dose of study medication in current study B5161004.
Arm/Group Title Sequence 1 Sequence 2 Sequence 3 Total
Hide Arm/Group Description:
In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
Sum of all participants in the study B5161004
Overall Number of Participants Analyzed 19 20 20 59
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
15.Primary Outcome
Title Summary of Pubertal Development by Tanner Stage
Hide Description

Tanner staging was performed before the first dose of this study to monitor for signs of accelerated sexual development. The physical changes in pubertal development (pubic hair, penis and testes) were assessed using the system described by Marshall and Tanner. Stage 1 is preadolescent, Stages 2, 3, and 4 are initiation of puberty and Stage 5 is mature adult. Details about the system can be referred to Tanner JM. Growth at Adolescence. Blackwell Scientific Publications 1962; 2nd edition.

Participant's Week 97 visit within study B5161002 (parent study) was collected as screening data.

Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.

Time Frame Screening, Baseline, Week 49.
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population included all participants who had received at least 1 dose of study medication in current study B5161004. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
Arm/Group Title Sequence 1 Sequence 2 Sequence 3 Total
Hide Arm/Group Description:
In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
Sum of all participants in the study B5161004
Overall Number of Participants Analyzed 19 20 20 59
Measure Type: Count of Participants
Unit of Measure: Participants
Public Hair, Not Detected (ND) Screening Number Analyzed 1 participants 1 participants 0 participants 2 participants
0
   0.0%
1
 100.0%
0
1
  50.0%
Public Hair, Stage 1, Screening Number Analyzed 1 participants 1 participants 0 participants 2 participants
1
 100.0%
0
   0.0%
0
1
  50.0%
Public Hair, Stage 2, Screening Number Analyzed 1 participants 1 participants 0 participants 2 participants
0
   0.0%
0
   0.0%
0
0
   0.0%
Public Hair, Stage 3, Screening Number Analyzed 1 participants 1 participants 0 participants 2 participants
0
   0.0%
0
   0.0%
0
0
   0.0%
Public Hair, Stage 4, Screening Number Analyzed 1 participants 1 participants 0 participants 2 participants
0
   0.0%
0
   0.0%
0
0
   0.0%
Public Hair, Stage 5, Screening Number Analyzed 1 participants 1 participants 0 participants 2 participants
0
   0.0%
0
   0.0%
0
0
   0.0%
Public Hair, ND, Baseline Number Analyzed 19 participants 20 participants 20 participants 59 participants
1
   5.3%
0
   0.0%
0
   0.0%
1
   1.7%
Public Hair, Stage 1, Baseline Number Analyzed 19 participants 20 participants 20 participants 59 participants
12
  63.2%
9
  45.0%
12
  60.0%
33
  55.9%
Public Hair, Stage 2, Baseline Number Analyzed 19 participants 20 participants 20 participants 59 participants
5
  26.3%
10
  50.0%
8
  40.0%
23
  39.0%
Public Hair, Stage 3, Baseline Number Analyzed 19 participants 20 participants 20 participants 59 participants
1
   5.3%
1
   5.0%
0
   0.0%
2
   3.4%
Public Hair, Stage 4, Baseline Number Analyzed 19 participants 20 participants 20 participants 59 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Public Hair, Stage 5, Baseline Number Analyzed 19 participants 20 participants 20 participants 59 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Public Hair, ND/NA, Week 49 Number Analyzed 7 participants 6 participants 8 participants 21 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Public Hair, Stage 1, Week 49 Number Analyzed 7 participants 6 participants 8 participants 21 participants
3
  42.9%
3
  50.0%
5
  62.5%
11
  52.4%
Public Hair, Stage 2 Week 49 Number Analyzed 7 participants 6 participants 8 participants 21 participants
4
  57.1%
3
  50.0%
3
  37.5%
10
  47.6%
Public Hair, Stage 3, Week 49 Number Analyzed 7 participants 6 participants 8 participants 21 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Public Hair, Stage 4, Week 49 Number Analyzed 7 participants 6 participants 8 participants 21 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Public Hair, Stage 5, Week 49 Number Analyzed 7 participants 6 participants 8 participants 21 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Penis, ND, Screening Number Analyzed 1 participants 1 participants 0 participants 2 participants
0
   0.0%
1
 100.0%
0
1
  50.0%
Penis, Stage 1, Screening Number Analyzed 1 participants 1 participants 0 participants 2 participants
1
 100.0%
0
   0.0%
0
1
  50.0%
Penis, Stage 2, Screening Number Analyzed 1 participants 1 participants 0 participants 2 participants
0
   0.0%
0
   0.0%
0
0
   0.0%
Penis, Stage 3, Screening Number Analyzed 1 participants 1 participants 0 participants 2 participants
0
   0.0%
0
   0.0%
0
0
   0.0%
Penis, Stage 4, Screening Number Analyzed 1 participants 1 participants 0 participants 2 participants
0
   0.0%
0
   0.0%
0
0
   0.0%
Penis, Stage 5, Screening Number Analyzed 1 participants 1 participants 0 participants 2 participants
0
   0.0%
0
   0.0%
0
0
   0.0%
Penis, ND / NA, Baseline Number Analyzed 19 participants 20 participants 20 participants 59 participants
1
   5.3%
0
   0.0%
0
   0.0%
1
   1.7%
Penis, Stage 1, Baseline Number Analyzed 19 participants 20 participants 20 participants 59 participants
13
  68.4%
11
  55.0%
11
  55.0%
35
  59.3%
Penis, Stage 2, Baseline Number Analyzed 19 participants 20 participants 20 participants 59 participants
5
  26.3%
9
  45.0%
9
  45.0%
23
  39.0%
Penis, Stage 3, Baseline Number Analyzed 19 participants 20 participants 20 participants 59 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Penis, Stage 4, Baseline Number Analyzed 19 participants 20 participants 20 participants 59 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Penis, Stage 5, Baseline Number Analyzed 19 participants 20 participants 20 participants 59 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Penis, ND, Week 49 Number Analyzed 7 participants 6 participants 8 participants 21 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Penis, Stage 1, Week 49 Number Analyzed 7 participants 6 participants 8 participants 21 participants
4
  57.1%
2
  33.3%
4
  50.0%
10
  47.6%
Penis, Stage 2, Week 49 Number Analyzed 7 participants 6 participants 8 participants 21 participants
3
  42.9%
4
  66.7%
3
  37.5%
10
  47.6%
Penis, Stage 3, Week 49 Number Analyzed 7 participants 6 participants 8 participants 21 participants
0
   0.0%
0
   0.0%
1
  12.5%
1
   4.8%
Penis, Stage 4, Week 49 Number Analyzed 7 participants 6 participants 8 participants 21 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Penis, Stage 5, Week 49 Number Analyzed 7 participants 6 participants 8 participants 21 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Testes, ND, Screening Number Analyzed 1 participants 1 participants 0 participants 2 participants
0
   0.0%
1
 100.0%
0
1
  50.0%
Testes, Stage 1, Screening Number Analyzed 1 participants 1 participants 0 participants 2 participants
1
 100.0%
0
   0.0%
0
1
  50.0%
Testes, Stage 2, Screening Number Analyzed 1 participants 1 participants 0 participants 2 participants
0
   0.0%
0
   0.0%
0
0
   0.0%
Testes, Stage 3, Screening Number Analyzed 1 participants 1 participants 0 participants 2 participants
0
   0.0%
0
   0.0%
0
0
   0.0%
Testes, Stage 4, Screening Number Analyzed 1 participants 1 participants 0 participants 2 participants
0
   0.0%
0
   0.0%
0
0
   0.0%
Testes, Stage 5, Screening Number Analyzed 1 participants 1 participants 0 participants 2 participants
0
   0.0%
0
   0.0%
0
0
   0.0%
Testes, ND, Baseline Number Analyzed 19 participants 20 participants 20 participants 59 participants
1
   5.3%
0
   0.0%
0
   0.0%
1
   1.7%
Testes, Stage 1, Baseline Number Analyzed 19 participants 20 participants 20 participants 59 participants
13
  68.4%
10
  50.0%
10
  50.0%
33
  55.9%
Testes, Stage 2, Baseline Number Analyzed 19 participants 20 participants 20 participants 59 participants
5
  26.3%
9
  45.0%
10
  50.0%
24
  40.7%
Testes, Stage 3, Baseline Number Analyzed 19 participants 20 participants 20 participants 59 participants
0
   0.0%
1
   5.0%
0
   0.0%
1
   1.7%
Testes, Stage 4, Baseline Number Analyzed 19 participants 20 participants 20 participants 59 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Testes, Stage 5, Baseline Number Analyzed 19 participants 20 participants 20 participants 59 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Testes, ND, Week 49 Number Analyzed 7 participants 6 participants 8 participants 21 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Testes, Stage 1, Week 49 Number Analyzed 7 participants 6 participants 8 participants 21 participants
4
  57.1%
4
  66.7%
1
  12.5%
9
  42.9%
Testes, Stage 2, Week 49 Number Analyzed 7 participants 6 participants 8 participants 21 participants
3
  42.9%
2
  33.3%
6
  75.0%
11
  52.4%
Testes, Stage 3, Week 49 Number Analyzed 7 participants 6 participants 8 participants 21 participants
0
   0.0%
0
   0.0%
1
  12.5%
1
   4.8%
Testes, Stage 4, Week 49 Number Analyzed 7 participants 6 participants 8 participants 21 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Testes, Stage 5, Week 49 Number Analyzed 7 participants 6 participants 8 participants 21 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
16.Primary Outcome
Title Summary of Testicular Volume
Hide Description

Testicular volume was used to monitor pubertal development. Participant's Week 97 visit within Study B5161002 (parent study) was collected as screening data in current study.

Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.

Time Frame Screening, Baseline, Week 49.
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population included all participants who had received at least 1 dose of study medication in current study B5161004. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
Arm/Group Title Sequence 1 Sequence 2 Sequence 3 Total
Hide Arm/Group Description:
In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
Sum of all participants in the study B5161004
Overall Number of Participants Analyzed 18 20 20 58
Mean (Standard Deviation)
Unit of Measure: Milliliter
Left Testis Volume - Screening Number Analyzed 1 participants 0 participants 0 participants 1 participants
3.0 [1]   (NA) 3.0 [1]   (NA)
Left Testis Volume - Baseline Number Analyzed 18 participants 20 participants 20 participants 58 participants
2.7  (1.07) 2.8  (1.06) 2.7  (1.63) 2.7  (1.27)
Left Testis Volume - Week 49 Number Analyzed 7 participants 6 participants 8 participants 21 participants
2.6  (0.98) 2.5  (0.55) 3.8  (3.41) 3.0  (2.19)
Right Testis Volume - Screening Number Analyzed 1 participants 0 participants 0 participants 1 participants
3.0 [1]   (NA) 3.0 [1]   (NA)
Right Testis Volume - Baseline Number Analyzed 18 participants 20 participants 20 participants 58 participants
2.7  (1.03) 2.8  (0.97) 2.6  (1.64) 2.7  (1.23)
Right Testis Volume - Week 49 Number Analyzed 7 participants 6 participants 8 participants 21 participants
2.6  (0.98) 2.5  (0.55) 3.6  (3.46) 3.0  (2.20)
[1]
This was individual testicular volume. Standard deviation was not applicable.
17.Primary Outcome
Title Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria - B5161004 Baseline
Hide Description

The number of participants pre-dose supine blood pressure and pulse rate meeting categorical summarization criteria are recorded in this table.

Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004.

(DBP=diastolic blood pressure, SBP=systolic blood pressure; The unit for blood pressure is: mmHg, the unit for pulse rate is: beats per minute [BPM])

Time Frame 2 Years
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population included all participants who had received at least 1 dose of study medication in current study B5161004. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
Arm/Group Title Sequence 1 Sequence 2 Sequence 3 Total
Hide Arm/Group Description:
In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
Sum of all participants in the study B5161004
Overall Number of Participants Analyzed 19 20 20 59
Measure Type: Count of Participants
Unit of Measure: Participants
Supine SBP - Observed Values <70+2×Age (2-10years) Number Analyzed 17 participants 12 participants 6 participants 35 participants
1
   5.9%
1
   8.3%
0
   0.0%
2
   5.7%
Supine SBP - Observed Values < 90 (11-17 years) Number Analyzed 2 participants 8 participants 14 participants 24 participants
0
   0.0%
1
  12.5%
1
   7.1%
2
   8.3%
Maximum Increase From Baseline in Supine SBP >=30 Number Analyzed 19 participants 20 participants 20 participants 59 participants
1
   5.3%
0
   0.0%
3
  15.0%
4
   6.8%
Maximum Decrease From Baseline in Supine SBP >=30 Number Analyzed 19 participants 20 participants 20 participants 59 participants
0
   0.0%
1
   5.0%
0
   0.0%
1
   1.7%
Supine DBP - Observed Values <50 (<18 years) Number Analyzed 19 participants 20 participants 20 participants 59 participants
1
   5.3%
1
   5.0%
2
  10.0%
4
   6.8%
Maximum Increase From Baseline in Supine DBP >=20 Number Analyzed 19 participants 20 participants 20 participants 59 participants
3
  15.8%
1
   5.0%
5
  25.0%
9
  15.3%
Maximum Decrease From Baseline in Supine DBP >=20 Number Analyzed 19 participants 20 participants 20 participants 59 participants
0
   0.0%
2
  10.0%
0
   0.0%
2
   3.4%
Supine Pulse Rate-Observed Values<40BPM(<18 years) Number Analyzed 19 participants 20 participants 20 participants 59 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Supine Pulse Rate-Observed Values>120BPM(<18years) Number Analyzed 19 participants 20 participants 20 participants 59 participants
2
  10.5%
0
   0.0%
1
   5.0%
3
   5.1%
18.Primary Outcome
Title Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria - Overall Baseline
Hide Description

The number of participants with data of pre-dose supine blood pressure meeting categorical summarization were recorded in this table.

Overall Baseline was defined as the last pre-dose assessment prior to the first day of dosing in study B5161002.

(DBP=diastolic blood pressure, SBP=systolic blood pressure; The unit for blood pressure is: mmHg).

Time Frame 2 Years
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population included all participants who had received at least 1 dose of study medication in current study B5161004.
Arm/Group Title Sequence 1 Sequence 2 Sequence 3 Total
Hide Arm/Group Description:
In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
Sum of all participants in the study B5161004
Overall Number of Participants Analyzed 19 20 20 59
Measure Type: Count of Participants
Unit of Measure: Participants
Maximum Increase From Baseline in Supine SBP >=30
2
  10.5%
6
  30.0%
2
  10.0%
10
  16.9%
Maximum Decrease From Baseline in Supine SBP >=30
0
   0.0%
3
  15.0%
4
  20.0%
7
  11.9%
Maximum Increase From Baseline in Supine DBP >=20
8
  42.1%
8
  40.0%
10
  50.0%
26
  44.1%
Maximum Decrease From Baseline in Supine DBP >=20
4
  21.1%
4
  20.0%
8
  40.0%
16
  27.1%
19.Primary Outcome
Title Number of Participants With Post-Baseline ECG Data Meeting Categorical Summarization Criteria - B5161004 Baseline
Hide Description

QTcF=QT/(60/Hour)**(1/3). Means of replicates were used in the calculations. QT=time between the start of the Q wave and the end of the T wave in the heart's electrical cycle; QTcF=corrected QT (Fridericia correction). All scheduled ECGs were performed after the participant had rested quietly for at least 10 minutes in a supine position.

Baseline was defined as the average of the last triplicate pre-dose measurements prior to Day 1 in B5161004.

Time Frame 2 Years
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population included all participants who had received at least 1 dose of study medication in current study B5161004 and who were evaluable for this outcome measure.
Arm/Group Title Sequence 1 Sequence 2 Sequence 3 Total
Hide Arm/Group Description:
In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
Sum of all participants in the study B5161004
Overall Number of Participants Analyzed 18 20 20 58
Measure Type: Count of Participants
Unit of Measure: Participants
Maximum(Max)QTcF Interval-ObservedValues<450msec
18
 100.0%
20
 100.0%
18
  90.0%
56
  96.6%
Max QTcF Interval -Observed Values450-<480msec
0
   0.0%
0
   0.0%
2
  10.0%
2
   3.4%
Max QTcF Interval -Observed Values480-<500msec
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Max QTcF Interval -Observed Values>=500msec
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Max QTcF Interval Increase From Baseline<30msec
16
  88.9%
20
 100.0%
18
  90.0%
54
  93.1%
Max QTcF Interval Increase From Baseline30-<60msec
2
  11.1%
0
   0.0%
0
   0.0%
2
   3.4%
Max QTcF Interval Increase From Baseline>= 60msec
0
   0.0%
0
   0.0%
2
  10.0%
2
   3.4%
20.Primary Outcome
Title Number of Participants With Post-Baseline ECG Data Meeting Categorical Summarization Criteria - Overall Baseline
Hide Description

QT=time between the start of the Q wave and the end of the T wave in the heart's electrical cycle; QTcF=corrected QT (Fridericia correction). All scheduled ECGs were performed after the participant had rested quietly for at least 10 minutes in a supine position.

Overall baseline was defined as the average of the last triplicate pre-dose measurements prior to the first day of dosing in study B5161002.

Time Frame 2 Years
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population included all participants who had received at least 1 dose of study medication in current study B5161004.
Arm/Group Title Sequence 1 Sequence 2 Sequence 3 Total
Hide Arm/Group Description:
In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
Sum of all participants in the study B5161004
Overall Number of Participants Analyzed 19 20 20 59
Measure Type: Count of Participants
Unit of Measure: Participants
Maximum QTcF Interval Increase From Baseline <30
11
  57.9%
15
  75.0%
17
  85.0%
43
  72.9%
Max-QTcF Interval IncreaseFromBaseline30-<60msec
7
  36.8%
5
  25.0%
1
   5.0%
13
  22.0%
Maximum QTcF Interval Increase From Baseline >=60
1
   5.3%
0
   0.0%
2
  10.0%
3
   5.1%
21.Primary Outcome
Title Number of Participants With Iron Accumulation Data Meeting Categorical Summarization Criteria
Hide Description

Liver Magnetic Resonance Imaging (MRIs) were sent to an independent central radiology imaging facility for calculation of the average R2* value which was used to monitor for iron accumulation in the liver. Mean R2* values had been used in the calculations.

Normal: R2* <= 75 Hz at 1.5 T or <=139 Hz at 3.0 T; Above Normal: R2* > 75 Hz and <= 190 Hz at 1.5 T or R2* > 139 Hz and <= 369 Hz at 3.0 T Mild overload: R2* > 190 Hz at 1.5 T or R2* > 369 Hz at 3.0 T Data from participant's Week 93 visit in Study B5161002 (parent study) were used for screening in the current study.

Time Frame Screening and Week 49.
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population included all participants who had received at least 1 dose of study medication in current study B5161004. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
Arm/Group Title Sequence 1 Sequence 2 Sequence 3 Total
Hide Arm/Group Description:
In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
Sum of all participants in the study B5161004
Overall Number of Participants Analyzed 19 20 20 59
Measure Type: Count of Participants
Unit of Measure: Participants
Screening - Normal Number Analyzed 19 participants 20 participants 20 participants 59 participants
19
 100.0%
20
 100.0%
20
 100.0%
59
 100.0%
Screening - Above Normal Number Analyzed 19 participants 20 participants 20 participants 59 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Screening - Mild Overload Number Analyzed 19 participants 20 participants 20 participants 59 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Week 49 - Normal Number Analyzed 7 participants 6 participants 8 participants 21 participants
7
 100.0%
6
 100.0%
8
 100.0%
21
 100.0%
Week 49 - Above Normal Number Analyzed 7 participants 6 participants 8 participants 21 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Week 49 - Mild Overload Number Analyzed 7 participants 6 participants 8 participants 21 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Total - Normal Number Analyzed 19 participants 20 participants 20 participants 59 participants
19
 100.0%
20
 100.0%
20
 100.0%
59
 100.0%
Total - Above Normal Number Analyzed 19 participants 20 participants 20 participants 59 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Total - Mild Overload Number Analyzed 19 participants 20 participants 20 participants 59 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
22.Primary Outcome
Title Change From Baseline in Left Ventricular Ejection Fraction (LVEF) by Cardiac MRI - B5161004 Baseline
Hide Description The LVEF was the ratio of blood ejected during systole to blood in the ventricle at the end of diastole. LVEF was measured by cardiac magnetic resonance imaging (MRI) or echocardiography. The same method of cardiac imaging was used consistently for each participant. Cardiac MRIs were read by a central imaging vendor, while echocardiograms were read locally (at each site). The table presents the results from cardiac MRIs. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.
Time Frame Baseline and Week 49.
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population included all participants who had received at least 1 dose of study medication in current study B5161004. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
Arm/Group Title Sequence 1 Sequence 2 Sequence 3 Total
Hide Arm/Group Description:
In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
Sum of all participants in the study B5161004
Overall Number of Participants Analyzed 19 20 20 59
Mean (Standard Deviation)
Unit of Measure: Ratio of Ejected Blood
Baseline - Observed Values Number Analyzed 2 participants 4 participants 5 participants 11 participants
56.000  (5.6569) 60.750  (2.2174) 62.400  (5.6833) 60.636  (4.8430)
Week 49 - Change From Baseline Number Analyzed 1 participants 0 participants 2 participants 3 participants
-3.000 [1]   (NA) -1.500  (4.9497) -2.000  (3.6056)
[1]
Standard deviation was not applicable for individual value.
23.Primary Outcome
Title Change From Baseline in Left Ventricular Ejection Fraction (LVEF) by Cardiac MRI - Overall Baseline
Hide Description

The LVEF was the ratio of blood ejected during systole to blood in the ventricle at the end of diastole. LVEF was measured by cardiac magnetic resonance imaging (MRI) or echocardiography. The same method of cardiac imaging was used consistently for each participant. Cardiac MRIs were read by a central imaging vendor, while echocardiograms were read locally (at each site). The table presents the results from cardiac MRIs.

Overall baseline was defined as the last pre-dose assessment prior to the first day of dosing in study B5161002. Week 1 was counted starting from the study treatment in study B5161002.

Time Frame Baseline, Weeks 49, 97, 146.
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population included all participants who had received at least 1 dose of study medication in current study B5161004. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
Arm/Group Title Sequence 1 Sequence 2 Sequence 3 Total
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In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
Sum of all participants in the study B5161004
Overall Number of Participants Analyzed 19 20 20 59
Mean (Standard Deviation)
Unit of Measure: Ratio of Ejected Blood
Baseline - Observed Values Number Analyzed 2 participants 4 participants 6 participants 12 participants
66.000  (8.4853) 61.250  (3.5000) 61.333  (5.3541) 62.083  (5.1250)
Week 49 - Change From Baseline Number Analyzed 2 participants 4 participants 5 participants 11 participants
-11.000  (2.8284) -3.500  (1.9149) 0.000  (7.4498) -3.273  (6.4357)
Week 97 - Change From Baseline Number Analyzed 2 participants 4 participants 5 participants 11 participants
-10.000  (2.8284) -0.500  (2.8868) -0.800  (6.5727) -2.364  (5.9038)
Week 146 - Change From Baseline Number Analyzed 1 participants 0 participants 2 participants 3 participants
-15.000 [1]   (NA) 3.500  (0.7071) -2.667  (10.6927)
[1]
Standard deviation was not applicable for individual value.
24.Primary Outcome
Title Change From Baseline in Left Ventricular Ejection Fraction (LVEF) by Echocardiogram - B5161004 Baseline
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The LVEF was the ratio of blood ejected during systole to blood in the ventricle at the end of diastole. LVEF was measured by cardiac magnetic resonance imaging (MRI) or echocardiography. The same method of cardiac imaging was used consistently for each participant. Cardiac MRIs were read by a central imaging vendor, while echocardiograms were read locally (at each site). The table presents the results from echocardiograms.

Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.

Time Frame Baseline, Week 49.
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Analysis population included all participants who had received at least 1 dose of study medication in current study B5161004. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
Arm/Group Title Sequence 1 Sequence 2 Sequence 3 Total
Hide Arm/Group Description:
In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
Sum of all participants in the study B5161004
Overall Number of Participants Analyzed 19 20 20 59
Mean (Standard Deviation)
Unit of Measure: Ratio of Ejected Blood
Baseline - Observed Values Number Analyzed 17 participants 17 participants 14 participants 48 participants
60.359  (3.7545) 62.461  (6.0180) 62.543  (5.3731) 61.740  (5.1170)
Week 49 - Change From Baseline Number Analyzed 5 participants 6 participants 5 participants 16 participants
-0.400  (5.0334) -3.900  (8.9252) 2.200  (7.6056) -0.900  (7.4580)
25.Primary Outcome
Title Change From Baseline in Left Ventricular Ejection Fraction (LVEF) by Echocardiogram - Overall Baseline
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The LVEF was the ratio of blood ejected during systole to blood in the ventricle at the end of diastole. LVEF was measured by cardiac magnetic resonance imaging (MRI) or echocardiography. The same method of cardiac imaging was used consistently for each participant. Cardiac MRIs were read by a central imaging vendor, while echocardiograms were read locally (at each site). The table presents the results from echocardiograms.

Overall baseline was defined as the last pre-dose assessment prior to the first day of dosing in study B5161002. Week 1 was counted starting from the study treatment in study B5161002.

Time Frame Baseline, Weeks 49, 97, 146.
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Analysis population included all participants who had received at least 1 dose of study medication in current study B5161004. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
Arm/Group Title Sequence 1 Sequence 2 Sequence 3 Total
Hide Arm/Group Description:
In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
Sum of all participants in the study B5161004
Overall Number of Participants Analyzed 19 20 20 59
Mean (Standard Deviation)
Unit of Measure: Ratio of Ejected Blood
Baseline - Observed Values Number Analyzed 17 participants 16 participants 15 participants 48 participants
63.288  (4.3743) 64.094  (4.3025) 64.073  (4.5848) 63.802  (4.3395)
Week 49 - Change From Baseline Number Analyzed 17 participants 15 participants 15 participants 47 participants
-0.171  (5.7432) -1.040  (4.8861) -0.213  (6.1487) -0.462  (5.5142)
Week 97 - Change From Baseline Number Analyzed 17 participants 16 participants 14 participants 47 participants
-2.929  (5.4060) -1.810  (6.1321) -1.414  (6.4799) -2.097  (5.8924)
Week 146 - Change From Baseline Number Analyzed 5 participants 6 participants 5 participants 16 participants
-1.240  (2.3416) -4.833  (4.2151) -1.440  (11.6993) -2.650  (6.8514)
26.Primary Outcome
Title Bone Age to Chronological Age Ratio
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Bone age assessment was evaluated by the ratio of the bone age to the chronological age using the X rays of the hand and wrist. Ratio of bone age to chronological age was calculated by bone age/chronological age at scan date. Chronological age at scan date was calculated by (scan date - date of birth + 1)/365.25.

Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.

Time Frame Baseline and Week 49.
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Hide Analysis Population Description
Analysis population included all participants who had received at least 1 dose of study medication in current study B5161004. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
Arm/Group Title Sequence 1 Sequence 2 Sequence 3 Total
Hide Arm/Group Description:
In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
Sum of all participants in the study B5161004
Overall Number of Participants Analyzed 19 20 20 59
Mean (Standard Deviation)
Unit of Measure: Ratio
Baseline Number Analyzed 19 participants 20 participants 20 participants 59 participants
0.76  (0.213) 0.74  (0.195) 0.81  (0.177) 0.77  (0.194)
Week 49 Number Analyzed 7 participants 6 participants 7 participants 20 participants
0.74  (0.197) 0.65  (0.157) 0.70  (0.172) 0.70  (0.172)
27.Primary Outcome
Title Whole Body and Spine DXA: Bone Mineral Density Z-Score, Height Adjusted Over Time
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Bone mineral density (BMD) was monitored by dual energy x-ray absorptiometry (DXA). DXA scans were obtained to evaluate bone mineral density of the spine and whole body without head.

The height adjusted Z-score presented below is the number of standard deviations which compares the BMD of the participant to the average BMD matched for their age, sex and ethnicity. If the Z-score was -2 standard deviations or lower, the result was "below the expected range for age". If the Z-score was above -2 standard deviations, the result was "within the expected range for age".

Time Frame Screening (Week 97 visit within parent study B5161002) and Week 49
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Analysis population included all participants who had received at least 1 dose of study medication in current study B5161004. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
Arm/Group Title Sequence