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Trial record 87 of 398 for:    bleeding episodes

BAX 855 Pediatric Study

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: NCT02210091
Recruitment Status : Completed
First Posted : August 6, 2014
Results First Posted : January 27, 2017
Last Update Posted : May 29, 2019
Sponsor:
Information provided by (Responsible Party):
Shire ( Baxalta now part of Shire )

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hemophilia A
Interventions Biological: Antihemophilic Factor (Recombinant) - Plasma/Albumin Free Method
Biological: PEGylated Recombinant Factor VIII
Enrollment 75
Recruitment Details 52 sites participated in this study. 39 study sites enrolled participants and 13 sites were initiated but were inactive.
Pre-assignment Details 73 participants enrolled and were screened for study participation. There were 9 screen failures. Among these, 2 participants were screen failures at first screening but entered the study later. 66 participants were dosed in the prophylactic part of the study, of whom 31 participants were also dosed in the PK part prior to prophylaxis.
Arm/Group Title <6 Years Old 6 to <12 Years Old
Hide Arm/Group Description [Not Specified] [Not Specified]
Period Title: Overall Study
Started 32 34
Completed 32 32
Not Completed 0 2
Reason Not Completed
Physician Decision             0             1
Withdrawal by Sponsor             0             1
Arm/Group Title <6 Years Old 6 to <12 Years Old Total
Hide Arm/Group Description [Not Specified] [Not Specified] Total of all reporting groups
Overall Number of Baseline Participants 32 34 66
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 32 participants 34 participants 66 participants
3.7  (1.17) 8.1  (1.92) 6.0  (2.70)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants 34 participants 66 participants
Female
0
   0.0%
1
   2.9%
1
   1.5%
Male
32
 100.0%
33
  97.1%
65
  98.5%
1.Primary Outcome
Title Number of Participants With Inhibitory Antibodies to Factor VIII (FVIII)
Hide Description Inhibitory antibodies to FVIII were measured using the Nijmegen modification of the Bethesda assay. Incidence of an FVIII inhibitory antibody was defined as an inhibitor level ≥0.6 Bethesda units [BU].
Time Frame After first exposure to BAX 855 until completion of study - approx. 6 months per participant.
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the BAX 855 Safety Analysis Set who developed an inhibitor at any time plus participants who did not develop an inhibitor, had 50 or more exposure days (EDs) to BAX 855 and had FVIII Inhibitory test results after 50 EDs.
Arm/Group Title <6 Years Old 6 to <12 Years Old BAX 855 Safety Analysis Set
Hide Arm/Group Description:
Participants < 6 years old who received at least one dose of BAX 855.
Participants 6 to <12 years old who received at least one dose of BAX 855.
Participants who received at least one dose of BAX 855.
Overall Number of Participants Analyzed 29 28 57
Measure Type: Number
Unit of Measure: participants
0 0 0
2.Secondary Outcome
Title Annualized Bleeding Rate (ABR)
Hide Description

The annualized bleeding rate (ABR) during the prophylaxis period was assessed based upon each individual bleeding episode, spontaneous or traumatic, recorded in the participant´s diary and/or recorded in the physician/nurse/study site notes.

The annualized bleeding rate was analyzed using a generalized linear model framework assuming a negative binomial distribution with a logarithmic link function and presence or absence of target joints and age cohort as covariates and duration of the observation period in years as offset. Point estimates for the mean and 95% confidence intervals are presented.

Time Frame During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs last
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Hide Analysis Population Description
Full Analysis Set: All participants who received at least 1 dose of BAX 855 in either PK or prophylaxis part of study
Arm/Group Title <6 Years Old 6 to <12 Years Old Full Analysis Set
Hide Arm/Group Description:
Participants <6 years old who received at least one dose of BAX 855 in either the Pharmacokinetic (PK) part of the study or the prophylaxis part of the study.
Participants 6 to <12 years old who received at least one dose of BAX 855 in either the Pharmacokinetic (PK) part of the study or the prophylaxis part of the study.
Participants who received at least one dose of BAX 855 in either the Pharmacokinetic (PK) part of the study or the prophylaxis part of the study.
Overall Number of Participants Analyzed 32 34 66
Mean (95% Confidence Interval)
Unit of Measure: bleeding episodes per year
Overall annualized bleeding rate
2.37
(1.486 to 3.778)
3.75
(2.429 to 5.781)
3.04
(2.208 to 4.186)
Annualized rate of joint bleeds
0.862
(0.381 to 1.946)
1.355
(0.648 to 2.833)
1.103
(0.637 to 1.910)
Annualized rate of target joint bleeds
0 [1] 
(0 to NA)
0 [1] 
(0 to NA)
0 [1] 
(0 to NA)
Annualized rate of non-target joint bleeds
0.763
(0.299 to 1.950)
0.998
(0.410 to 2.430)
0.892
(0.466 to 1.706)
Annualized spontaneous bleeding rate
1.018
(0.523 to 1.978)
1.316
(0.710 to 2.438)
1.164
(0.740 to 1.832)
Annualized rate of injury-related bleeds
1.628
(0.989 to 2.679)
2.586
(1.639 to 4.080)
2.089
(1.492 to 2.925)
[1]
NA = infinity
3.Secondary Outcome
Title Consumption of BAX 855: Number of Prophylactic Infusions Per Month Per Participant
Hide Description [Not Specified]
Time Frame During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs last
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Hide Analysis Population Description
BAX 855 Safety Analysis Set.
Arm/Group Title <6 Years Old 6 to <12 Years Old BAX 855 Safety Analysis Set
Hide Arm/Group Description:
Participants < 6 years old who received at least one dose of BAX 855.
Participants 6 to <12 years old who received at least one dose of BAX 855.
Participants who received at least one dose of BAX 855.
Overall Number of Participants Analyzed 32 34 66
Mean (Standard Deviation)
Unit of Measure: infusions per month
8.07  (0.245) 7.72  (0.974) 7.89  (0.736)
4.Secondary Outcome
Title Consumption of BAX 855: Number of Prophylactic Infusions Per Year (Annualized) Per Participant
Hide Description [Not Specified]
Time Frame During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs last
Hide Outcome Measure Data
Hide Analysis Population Description
BAX 855 Safety Analysis Set.
Arm/Group Title <6 Years Old 6 to <12 Years Old BAX 855 Safety Analysis Set
Hide Arm/Group Description:
Participants < 6 years old who received at least one dose of BAX 855.
Participants 6 to <12 years old who received at least one dose of BAX 855.
Participants who received at least one dose of BAX 855.
Overall Number of Participants Analyzed 32 34 66
Mean (Standard Deviation)
Unit of Measure: infusions per year
96.82  (2.942) 92.61  (11.693) 94.65  (8.834)
5.Secondary Outcome
Title Consumption of BAX 855: Weight-adjusted Dose of Prophylactic Infusions Per Month Per Participant
Hide Description [Not Specified]
Time Frame During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs last
Hide Outcome Measure Data
Hide Analysis Population Description
BAX 855 Safety Analysis Set.
Arm/Group Title <6 Years Old 6 to <12 Years Old BAX 855 Safety Analysis Set
Hide Arm/Group Description:
Participants < 6 years old who received at least one dose of BAX 855.
Participants 6 to <12 years old who received at least one dose of BAX 855.
Participants who received at least one dose of BAX 855.
Overall Number of Participants Analyzed 32 34 66
Mean (Standard Deviation)
Unit of Measure: IU/kg
458.93  (46.161) 455.86  (76.101) 457.35  (62.919)
6.Secondary Outcome
Title Consumption of BAX 855: Weight-adjusted Dose of Prophylactic Infusions Per Year (Annualized) Per Participant
Hide Description [Not Specified]
Time Frame During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs last
Hide Outcome Measure Data
Hide Analysis Population Description
BAX 855 Safety Analysis Set.
Arm/Group Title <6 Years Old 6 to <12 Years Old BAX 855 Safety Analysis Set
Hide Arm/Group Description:
Participants < 6 years old who received at least one dose of BAX 855.
Participants 6 to <12 years old who received at least one dose of BAX 855.
Participants who received at least one dose of BAX 855.
Overall Number of Participants Analyzed 32 34 66
Mean (Standard Deviation)
Unit of Measure: IU/kg
5507.20  (553.931) 5470.32  (913.210) 5488.20  (755.033)
7.Secondary Outcome
Title Consumption of BAX 855: Number of Infusions Per Bleeding Episode
Hide Description [Not Specified]
Time Frame During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs last
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the BAX 855 Safety Analysis Set who had treated bleeding episodes.
Arm/Group Title <6 Years Old 6 to <12 Years Old BAX 855 Safety Analysis Set
Hide Arm/Group Description:
Participants < 6 years old who received at least one dose of BAX 855.
Participants 6 to <12 years old who received at least one dose of BAX 855.
Participants who received at least one dose of BAX 855.
Overall Number of Participants Analyzed 15 19 34
Mean (Standard Deviation)
Unit of Measure: infusions
1.17  (0.362) 1.40  (0.655) 1.30  (0.551)
8.Secondary Outcome
Title Consumption of BAX 855: Weight-adjusted Dose Per Bleeding Episode
Hide Description [Not Specified]
Time Frame During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs last
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the BAX 855 Safety Analysis Set who had treated bleeding episodes.
Arm/Group Title <6 Years Old 6 to <12 Years Old BAX 855 Safety Analysis Set
Hide Arm/Group Description:
Participants < 6 years old who received at least one dose of BAX 855.
Participants 6 to <12 years old who received at least one dose of BAX 855.
Participants who received at least one dose of BAX 855.
Overall Number of Participants Analyzed 15 19 34
Overall Number of Units Analyzed
Type of Units Analyzed: Bleeding episodes
25 45 70
Mean (Standard Deviation)
Unit of Measure: IU/kg
Average dose to treat bleeding episode 52.21  (16.681) 62.31  (38.764) 57.85  (31.041)
Average dose per infusion per bleeding episode 45.58  (10.750) 43.76  (15.304) 44.56  (13.327)
9.Secondary Outcome
Title Hemostatic Efficacy Rating for Bleeding Episodes Treated With BAX 855 at Resolution of Bleed
Hide Description

Rating Scale for Treatment of Bleeding Episodes (BEs) (4-point ordinal scale):

Excellent: Full relief of pain and cessation of objective signs of bleeding (eg, swelling, tenderness, and decreased range of motion in the case of musculoskeletal hemorrhage) after a single infusion. No additional infusion required for the control of bleeding. Administration of further infusions to maintain hemostasis did not affect this scoring.

Good: Definite pain relief and/or improvement in signs of bleeding after a single infusion. Possibly requires more than 1 infusion for complete resolution.

Fair: Probable and/or slight relief of pain and slight improvement in signs of bleeding after single infusion. Required more than 1 infusion for complete resolution.

None: No improvement or condition worsens.

Time Frame After first exposure to BAX 855 until completion of study - approx. 6 months per participant.
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set who had treated bleeding episodes.
Arm/Group Title <6 Years Old 6 to <12 Years Old Full Analysis Set
Hide Arm/Group Description:
Participants <6 years old who received at least one dose of BAX 855.
Participants 6 to <12 years old who received at least one dose of BAX 855.
Participants who received at least one dose of BAX 855.
Overall Number of Participants Analyzed 15 19 34
Overall Number of Units Analyzed
Type of Units Analyzed: Bleeding episodes
25 45 70
Measure Type: Number
Unit of Measure: bleeding episodes
Excellent 15 19 34
Good 9 20 29
Fair 1 3 4
Not reported 0 3 3
10.Secondary Outcome
Title Serious Adverse Events (SAEs) Possibly or Probably Related to BAX 855
Hide Description [Not Specified]
Time Frame After first exposure to BAX 855 until completion of study - approx. 6 months per participant.
Hide Outcome Measure Data
Hide Analysis Population Description
BAX 855 Safety Analysis Set.
Arm/Group Title <6 Years Old 6 to <12 Years Old BAX 855 Safety Analysis Set
Hide Arm/Group Description:
Participants <6 years old who received at least one dose of BAX 855.
Participants 6 to <12 years old who received at least one dose of BAX 855.
Participants who received at least one dose of BAX 855.
Overall Number of Participants Analyzed 32 34 66
Measure Type: Number
Unit of Measure: serious adverse events
Investigator Assessment 0 0 0
Sponsor Assessment 0 0 0
11.Secondary Outcome
Title Non-serious Adverse Events Possibly or Probably Related to BAX 855
Hide Description [Not Specified]
Time Frame After first exposure to BAX 855 until completion of study - approx. 6 months per participant.
Hide Outcome Measure Data
Hide Analysis Population Description
BAX 855 Safety Analysis Set.
Arm/Group Title <6 Years Old 6 to <12 Years Old BAX 855 Safety Analysis Set
Hide Arm/Group Description:
Participants <6 years old who received at least one dose of BAX 855.
Participants 6 to <12 years old who received at least one dose of BAX 855.
Participants who received at least one dose of BAX 855.
Overall Number of Participants Analyzed 32 34 66
Measure Type: Number
Unit of Measure: adverse events
Investigator Assessment 1 0 0
Sponsor Assessment 0 0 0
12.Secondary Outcome
Title Number of Participants With Clinically Significant Changes in Vital Signs
Hide Description Vital signs: body temperature (°C), respiratory rate (breaths/min), pulse rate (beats/min), and systolic and diastolic blood pressure (mmHg). For each vital sign value that changed from normal at baseline to abnormal at any subsequent study visit, the Investigator determined if the value was clinically significant (i.e. and adverse event), or not.
Time Frame After first exposure to BAX 855 until completion of study - approx. 6 months per participant.
Hide Outcome Measure Data
Hide Analysis Population Description
BAX 855 Safety Analysis Set.
Arm/Group Title <6 Years Old 6 to <12 Years Old BAX 855 Safety Analysis Set
Hide Arm/Group Description:
Participants <6 years old who received at least one dose of BAX 855.
Participants 6 to <12 years old who received at least one dose of BAX 855.
Participants who received at least one dose of BAX 855.
Overall Number of Participants Analyzed 32 34 66
Measure Type: Number
Unit of Measure: participants
1 0 0
13.Secondary Outcome
Title Number of Clinically Significant Changes in Clinical Laboratory Parameters (Hematology, Clinical Chemistry, Lipids)
Hide Description

The HEMATOLOGY PANEL consisted of complete blood count: hemoglobin, hematocrit, erythrocytes (ie, red blood cell count), leukocytes (ie, white blood cell count) with differential (ie, basophils, eosinophils, lymphocytes, monocytes, and neutrophils), mean corpuscular volume, mean corpuscular hemoglobin concentration, and platelet count.

The CLINICAL CHEMISTRY PANEL consisted of sodium, potassium, chloride, bicarbonate, total protein, albumin, ALT, aspartate aminotransferase (AST), total bilirubin, alkaline phosphatase, blood urea nitrogen, creatinine, and glucose.

The LIPID PANEL consisted of cholesterol, very low density lipoprotein, low density lipoprotein, high density lipoprotein, and triglycerides.

For each laboratory parameter value that changed from normal at baseline to abnormal at any subsequent study visit, the Investigator determined if the value was clinically significant, or not.

Time Frame After first exposure to BAX 855 until completion of study - approx. 6 months per participant.
Hide Outcome Measure Data
Hide Analysis Population Description
BAX 855 Safety Analysis Set.
Arm/Group Title <6 Years Old 6 to <12 Years Old BAX 855 Safety Analysis Set
Hide Arm/Group Description:
Participants <6 years old who received at least one dose of BAX 855.
Participants 6 to <12 years old who received at least one dose of BAX 855.
Participants who received at least one dose of BAX 855.
Overall Number of Participants Analyzed 32 34 66
Measure Type: Number
Unit of Measure: clinically significant findings
Hematology-CS Rise in Eosinophils 1 0 1
Clin. Chemistry-CS Rise in Alkaline Phosphatase 1 0 1
14.Secondary Outcome
Title Positive Post-baseline Binding Antibodies to Factor VIII (FVIII), Polyethylene Glycol-Factor VIII (PEG-FVIII), PEG and Chinese Hamster Ovary (CHO) Proteins
Hide Description

Binding antibodies to FVIII and PEG-FVIII, as well as to PEG, were measured using enzyme-linked immunosorbent assay (ELISA). Both immunoglobulin G (IgG) and immunoglobulin M (IgM) binding antibodies for FVIII, BAX 855, and PEG were tested at each study visit. Testing for binding antibodies to CHO was performed on citrate-anti-coagulated plasma using an ELISA employing polyclonal anti-human IgG antibodies.

This outcome measure includes antibodies that were transient (antibody developed after exposure to BAX 855 but not present at study termination/completion) and pre-existent (antibody originally present before exposure to BAX 855).

Time Frame After first exposure to BAX 855 until completion of study - approx. 6 months per participant.
Hide Outcome Measure Data
Hide Analysis Population Description
BAX 855 Safety Analysis Set: Data not available for 1 participant in the 6 to <12 years group as participant was prematurely withdrawn from study.
Arm/Group Title <6 Years Old 6 to <12 Years Old BAX 855 Safety Analysis Set
Hide Arm/Group Description:
Participants <6 years old who received at least one dose of BAX 855.
Participants 6 to <12 years old who received at least one dose of BAX 855.
Participants who received at least one dose of BAX 855.
Overall Number of Participants Analyzed 32 33 65
Measure Type: Number
Unit of Measure: participants
Positive binding IgG antibodies to FVIII 0 0 0
Positive binding IgM antibodies to FVIII 0 0 0
Positive binding IgG antibodies to PEG-FVIII 3 4 7
Positive binding IgM antibodies to PEG-FVIII 0 0 0
Positive binding IgG antibodies to PEG 0 0 0
Positive binding IgM antibodies to PEG 0 0 0
Positive binding Ig antibodies to CHO 0 0 0
15.Secondary Outcome
Title Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve From 0 to ∞ Hours Post-infusion (AUC0-∞)
Hide Description

The first PK infusion was ADVATE and the second PK infusion was BAX 855. All participants undergoing PK assessment had a 72-hour washout period before administration of ADVATE and BAX 855. There were 4 blood draws for PK analysis-1 pre-infusion and 3 post infusion. The timing of the infusion (morning [am] or afternoon [pm]) and the timing of Blood Draws 3 and 4 (3 groups for each blood draw) were determined at randomization.

The sequence was as follows:- Blood Draw 1. within 30 minutes pre-infusion [Day 0]; PK INFUSION - am or pm [Day 0]; Blood Draw 2. 15-30 minutes post-infusion [Day 0]; Blood Draw 3. 3 groups:- 7 hours post-infusion (if am PK infusion) or 4 hours post-infusion (if pm PK infusion) [Day 0], Day 1 am or Day 1 pm; Blood Draw 4. 3 groups:- Day 2, Day 3 or Day 4. A nonlinear mixed effects model approach (population PK) was implemented to analyze PK data. A one-stage clotting assay was used as the primary assay and a chromogenic assay was used to provide supportive data.

Time Frame (1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4
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Hide Analysis Population Description
Pharmacokinetic (PK) Analysis Set.
Arm/Group Title PK Analysis Set - <6 Years Old PK Analysis Set - 6 to <12 Years Old PK Analysis Set
Hide Arm/Group Description:
Participants <6 years old who had been treated with at least 1 dose of ADVATE (60 ±5 IU/kg) and 1 dose of BAX 855 (60 ±5 IU/kg) in the pharmacokinetic (PK) part of the study (prior to prophylactic treatment) and had at least 1 PK concentration available for population PK and non-compartmental analysis.
Participants 6 to <12 years olde who had been treated with at least 1 dose of ADVATE (60 ±5 IU/kg) and 1 dose of BAX 855 (60 ±5 IU/kg) in the pharmcokinetic (PK) part of the study (prior to prophylactic treatment) and had at least 1 PK concentration available for population PK and non-compartmental analysis.
Participants who had been treated with at least 1 dose of ADVATE (60 ±5 IU/kg) and 1 dose of BAX 855 (60 ±5 IU/kg) in the pharmacokinetic (PK) part of the study (prior to prophylactic treatment) and had at least 1 PK concentration available for population PK and non-compartmental analysis.
Overall Number of Participants Analyzed 14 17 31
Mean (Standard Deviation)
Unit of Measure: IU•hr/L
One stage clotting assay - ADVATE 14000  (3070) 14400  (1800) 14200  (2420)
Chromogenic assay - ADVATE 11600  (3070) 16600  (3290) 14400  (4040)
One stage clotting assay - BAX 855 19500  (7580) 20100  (4930) 19800  (6160)
Chromogenic assay - BAX 855 21900  (15900) 22600  (5140) 22300  (11200)
16.Secondary Outcome
Title Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve From 0 to ∞ Hours Post-infusion Per Dose, (AUC0-∞/Dose)
Hide Description [Not Specified]
Time Frame (1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
The PK parameters were derived using a non-compartmental estimation approach using a flexible sampling design to provide point and interval estimates for summary PK parameter using a batch method. AUC/Dose is not a standard output parameter so this calculation was not done.
Arm/Group Title Overall Study Arm
Hide Arm/Group Description:
[Not Specified]
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
17.Secondary Outcome
Title Pharmacokinetics (PK): Mean Residence Time (MRT)
Hide Description

The first PK infusion was ADVATE and the second PK infusion was BAX 855. All participants undergoing PK assessment had a 72-hour washout period before administration of ADVATE and BAX 855. There were 4 blood draws for PK analysis-1 pre-infusion and 3 post infusion. The timing of the infusion (morning [am] or afternoon [pm]) and the timing of Blood Draws 3 and 4 (3 groups for each blood draw) were determined at randomization.

The sequence was as follows:- Blood Draw 1. within 30 minutes pre-infusion [Day 0]; PK INFUSION - am or pm [Day 0]; Blood Draw 2. 15-30 minutes post-infusion [Day 0]; Blood Draw 3. 3 groups:- 7 hours post-infusion (if am PK infusion) or 4 hours post-infusion (if pm PK infusion) [Day 0], Day 1 am or Day 1 pm; Blood Draw 4. 3 groups:- Day 2, Day 3 or Day 4. A nonlinear mixed effects model approach (population PK) was implemented to analyze PK data. A one-stage clotting assay was used as the primary assay and a chromogenic assay was used to provide supportive data.

Time Frame (1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) Analysis Set
Arm/Group Title PK Analysis Set - <6 Years Old PK Analysis Set - 6 to <12 Years Old PK Analysis Set
Hide Arm/Group Description:
Participants <6 years old who had been treated with at least 1 dose of ADVATE (60 ±5 IU/kg) and 1 dose of BAX 855 (60 ±5 IU/kg) in the pharmacokinetic (PK) part of the study (prior to prophylactic treatment) and had at least 1 PK concentration available for population PK and non-compartmental analysis.
Participants 6 to <12 years old who had been treated with at least 1 dose of ADVATE (60 ±5 IU/kg) and 1 dose of BAX 855 (60 ±5 IU/kg) in the pharmcokinetic (PK) part of the study (prior to prophylactic treatment) and had at least 1 PK concentration available for population PK and non-compartmental analysis.
Participants who had been treated with at least 1 dose of ADVATE (60 ±5 IU/kg) and 1 dose of BAX 855 (60 ±5 IU/kg) in the pharmacokinetic (PK) part of the study (prior to prophylactic treatment) and had at least 1 PK concentration available for population PK and non-compartmental analysis.
Overall Number of Participants Analyzed 14 17 31
Mean (Standard Deviation)
Unit of Measure: hours (hr)
One stage clotting assay - ADVATE 13.3  (3.95) 14.2  (2.64) 13.8  (3.27)
Chromogenic assay - ADVATE 12.5  (2.52) 11.6  (1.20) 12.0  (1.93)
One stage clotting assay - BAX 855 17.0  (3.51) 17.8  (2.40) 17.5  (2.93)
Chromogenic assay - BAX 855 18.7  (12.6) 17.2  (3.72) 17.9  (8.76)
18.Secondary Outcome
Title Pharmacokinetics (PK): Clearance (CL)
Hide Description

The first PK infusion was ADVATE and the second PK infusion was BAX 855. All participants undergoing PK assessment had a 72-hour washout period before administration of ADVATE and BAX 855. There were 4 blood draws for PK analysis-1 pre-infusion and 3 post infusion. The timing of the infusion (morning [am] or afternoon [pm]) and the timing of Blood Draws 3 and 4 (3 groups for each blood draw) were determined at randomization.

The sequence was as follows:- Blood Draw 1. within 30 minutes pre-infusion [Day 0]; PK INFUSION - am or pm [Day 0]; Blood Draw 2. 15-30 minutes post-infusion [Day 0]; Blood Draw 3. 3 groups:- 7 hours post-infusion (if am PK infusion) or 4 hours post-infusion (if pm PK infusion) [Day 0], Day 1 am or Day 1 pm; Blood Draw 4. 3 groups:- Day 2, Day 3 or Day 4. A nonlinear mixed effects model approach (population PK) was implemented to analyze PK data. A one-stage clotting assay was used as the primary assay and a chromogenic assay was used to provide supportive data.

Time Frame (1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) Analysis Set
Arm/Group Title PK Analysis Set - <6 Years Old PK Analysis Set - 6 to <12 Years Old PK Analysis Set
Hide Arm/Group Description:
Participants <6 years old who had been treated with at least 1 dose of ADVATE (60 ±5 IU/kg) and 1 dose of BAX 855 (60 ±5 IU/kg) in the pharmacokinetic (PK) part of the study (prior to prophylactic treatment) and had at least 1 PK concentration available for population PK and non-compartmental analysis.
Participants 6 to <12 years old who had been treated with at least 1 dose of ADVATE (60 ±5 IU/kg) and 1 dose of BAX 855 (60 ±5 IU/kg) in the pharmcokinetic (PK) part of the study (prior to prophylactic treatment) and had at least 1 PK concentration available for population PK and non-compartmental analysis.
Participants who had been treated with at least 1 dose of ADVATE (60 ±5 IU/kg) and 1 dose of BAX 855 (60 ±5 IU/kg) in the pharmacokinetic (PK) part of the study (prior to prophylactic treatment) and had at least 1 PK concentration available for population PK and non-compartmental analysis.
Overall Number of Participants Analyzed 14 17 31
Mean (Standard Deviation)
Unit of Measure: L/hr
One stage clotting assay - ADVATE 0.0775  (0.0132) 0.1250  (0.04200) 0.1030  (0.0398)
Chromogenic assay - ADVATE 0.0933  (0.0106) 0.1040  (0.00875) 0.0994  (0.0110)
One stage clotting assay - BAX 855 0.0596  (0.0190) 0.0913  (0.0276) 0.0770  (0.0286)
Chromogenic assay - BAX 855 0.0574  (0.0174) 0.0812  (0.0248) 0.0704  (0.0246)
19.Secondary Outcome
Title Pharmacokinetics (PK): Plasma Half-life (T1/2)
Hide Description

The first PK infusion was ADVATE and the second PK infusion was BAX 855. All participants undergoing PK assessment had a 72-hour washout period before administration of ADVATE and BAX 855. There were 4 blood draws for PK analysis-1 pre-infusion and 3 post infusion. The timing of the infusion (morning [am] or afternoon [pm]) and the timing of Blood Draws 3 and 4 (3 groups for each blood draw) were determined at randomization.

The sequence was as follows:- Blood Draw 1. within 30 minutes pre-infusion [Day 0]; PK INFUSION - am or pm [Day 0]; Blood Draw 2. 15-30 minutes post-infusion [Day 0]; Blood Draw 3. 3 groups:- 7 hours post-infusion (if am PK infusion) or 4 hours post-infusion (if pm PK infusion) [Day 0], Day 1 am or Day 1 pm; Blood Draw 4. 3 groups:- Day 2, Day 3 or Day 4. A nonlinear mixed effects model approach (population PK) was implemented to analyze PK data. A one-stage clotting assay was used as the primary assay and a chromogenic assay was used to provide supportive data.

Time Frame (1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4
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Pharmacokinetic (PK) Analysis Set
Arm/Group Title PK Analysis Set - <6 Years Old PK Analysis Set - 6 to <12 Years Old PK Analysis Set
Hide Arm/Group Description:
Participants <6 years old who had been treated with at least 1 dose of ADVATE (60 ±5 IU/kg) and 1 dose of BAX 855 (60 ±5 IU/kg) in the pharmacokinetic (PK) part of the study (prior to prophylactic treatment) and had at least 1 PK concentration available for population PK and non-compartmental analysis.
Participants 6 to <12 years old who had been treated with at least 1 dose of ADVATE (60 ±5 IU/kg) and 1 dose of BAX 855 (60 ±5 IU/kg) in the pharmcokinetic (PK) part of the study (prior to prophylactic treatment) and had at least 1 PK concentration available for population PK and non-compartmental analysis.
Participants who had been treated with at least 1 dose of ADVATE (60 ±5 IU/kg) and 1 dose of BAX 855 (60 ±5 IU/kg) in the pharmacokinetic (PK) part of the study (prior to prophylactic treatment) and had at least 1 PK concentration available for population PK and non-compartmental analysis.
Overall Number of Participants Analyzed 14 17 31
Mean (Standard Deviation)
Unit of Measure: hours (hr)
One stage clotting assay - ADVATE 9.24  (2.74) 9.82  (1.83) 9.56  (2.26)
Chromogenic assay - ADVATE 8.68  (1.75) 8.04  (0.83) 8.33  (1.34)
One stage clotting assay - BAX 855 11.8  (2.43) 12.4  (1.67) 12.1  (2.03)
Chromogenic assay - BAX 855 13.0  (8.74) 11.9  (2.58) 12.4  (6.07)
20.Secondary Outcome
Title Pharmacokinetics (PK): Volume of Distribution at Steady State (Vss)
Hide Description

The first PK infusion was ADVATE and the second PK infusion was BAX 855. All participants undergoing PK assessment had a 72-hour washout period before administration of ADVATE and BAX 855. There were 4 blood draws for PK analysis-1 pre-infusion and 3 post infusion. The timing of the infusion (morning [am] or afternoon [pm]) and the timing of Blood Draws 3 and 4 (3 groups for each blood draw) were determined at randomization.

The sequence was as follows:- Blood Draw 1. within 30 minutes pre-infusion [Day 0]; PK INFUSION - am or pm [Day 0]; Blood Draw 2. 15-30 minutes post-infusion [Day 0]; Blood Draw 3. 3 groups:- 7 hours post-infusion (if am PK infusion) or 4 hours post-infusion (if pm PK infusion) [Day 0], Day 1 am or Day 1 pm; Blood Draw 4. 3 groups:- Day 2, Day 3 or Day 4. A nonlinear mixed effects model approach (population PK) was implemented to analyze PK data. A one-stage clotting assay was used as the primary assay and a chromogenic assay was used to provide supportive data.

Time Frame (1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4
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Hide Analysis Population Description
Pharmacokinetic (PK) Analysis Set
Arm/Group Title PK Analysis Set <6 Years Old PK Analysis Set - 6 to <12 Years Old PK Analysis Set
Hide Arm/Group Description:
Participants <6 years old who had been treated with at least 1 dose of ADVATE (60 ±5 IU/kg) and 1 dose of BAX 855 (60 ±5 IU/kg) in the pharmacokinetic (PK) part of the study (prior to prophylactic treatment) and had at least 1 PK concentration available for population PK and non-compartmental analysis.
Participants 6 to <12 years old who had been treated with at least 1 dose of ADVATE (60 ±5 IU/kg) and 1 dose of BAX 855 (60 ±5 IU/kg) in the pharmcokinetic (PK) part of the study (prior to prophylactic treatment) and had at least 1 PK concentration available for population PK and non-compartmental analysis.
Participants who had been treated with at least 1 dose of ADVATE (60 ±5 IU/kg) and 1 dose of BAX 855 (60 ±5 IU/kg) in the pharmacokinetic (PK) part of the study (prior to prophylactic treatment) and had at least 1 PK concentration available for population PK and non-compartmental analysis.
Overall Number of Participants Analyzed 14 17 31
Mean (Standard Deviation)
Unit of Measure: litre (L)
One stage clotting assay - ADVATE 1.02  (0.302) 1.69  (0.350) 1.39  (0.470)
Chromogenic assay - ADVATE 1.14  (0.107) 1.20  (0.0548) 1.18  (0.0857)
One stage clotting assay - BAX 855 0.97  (0.230) 1.59  (0.343) 1.31  (0.427)
Chromogenic assay - BAX 855 0.907  (0.124) 1.33  (0.233) 1.14  (0.285)
21.Secondary Outcome
Title Pharmacokinetics (PK): Incremental Recovery (IR)
Hide Description

The first PK infusion was ADVATE and the second PK infusion was BAX 855. All participants undergoing PK assessment had a 72-hour washout period before administration of ADVATE and BAX 855. There were 4 blood draws for PK analysis-1 pre-infusion and 3 post infusion. The timing of the infusion (morning [am] or afternoon [pm]) and the timing of Blood Draws 3 and 4 (3 groups for each blood draw) were determined at randomization.

The sequence was as follows:- Blood Draw 1. within 30 minutes pre-infusion [Day 0]; PK INFUSION - am or pm [Day 0]; Blood Draw 2. 15-30 minutes post-infusion [Day 0]; Blood Draw 3. 3 groups:- 7 hours post-infusion (if am PK infusion) or 4 hours post-infusion (if pm PK infusion) [Day 0], Day 1 am or Day 1 pm; Blood Draw 4. 3 groups:- Day 2, Day 3 or Day 4. A non-compartmental model approach was implemented to analyze IR data. A one-stage clotting assay was used as the primary assay and a chromogenic assay was used to provide supportive data.

Time Frame (1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) Analysis Set
Arm/Group Title PK Analysis Set - <6 Years Old PK Analysis Set - 6 to <12 Years Old PK Analysis Set
Hide Arm/Group Description:
Participants <6 years old who had been treated with at least 1 dose of ADVATE (60 ±5 IU/kg) and 1 dose of BAX 855 (60 ±5 IU/kg) in the pharmacokinetic (PK) part of the study (prior to prophylactic treatment) and had at least 1 PK concentration available for population PK and non-compartmental analysis.
Participants 6 to <12 years old who had been treated with at least 1 dose of ADVATE (60 ±5 IU/kg) and 1 dose of BAX 855 (60 ±5 IU/kg) in the pharmcokinetic (PK) part of the study (prior to prophylactic treatment) and had at least 1 PK concentration available for population PK and non-compartmental analysis.
Participants who had been treated with at least 1 dose of ADVATE (60 ±5 IU/kg) and 1 dose of BAX 855 (60 ±5 IU/kg) in the pharmacokinetic (PK) part of the study (prior to prophylactic treatment) and had at least 1 PK concentration available for population PK and non-compartmental analysis.
Overall Number of Participants Analyzed 14 17 31
Mean (Standard Deviation)
Unit of Measure: IU/dL : IU/kg
One stage clotting assay - ADVATE 1.8563  (0.76004) 1.8696  (0.25856) 1.8636  (0.53481)
Chromogenic assay - ADVATE 1.7374  (0.29110) 2.0458  (0.31739) 1.9065  (0.33879)
One stage clotting assay - BAX 855 1.8809  (0.48894) 1.9342  (0.47451) 1.9101  (0.47371)
Chromogenic assay - BAX 855 1.8813  (0.27069) 2.1710  (0.38472) 2.0402  (0.36355)
22.Secondary Outcome
Title Pharmacokinetics (PK): Incremental Recovery (IR) of BAX 855 Over Time - One Stage Clotting Assay
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Pre- and post-infusion levels of Factor VIII (FVIII) following infusion of BAX 855 were used to determine IR.

For participants who underwent PK evaluation, baseline IR was determined from the IR measurement used in the PK analysis. Refer to data in Outcome measure 21- "Pharmacokinetics (PK): Incremental Recovery (IR)", for the category "One stage clotting assay - BAX 855"

For participants who did not undergo a PK evaluation, baseline IR was determined at the baseline visit prior to the prophylactic treatment phase and is included in this outcome measure.

Category title includes number of participants [n] < 6 yrs; ≥6 to <12 yrs and the Full Analysis Set, respectively.

Time Frame Baseline, Week 5 (or 10-15 EDs, whichever occurs last), Week 12, and Month 6 (Completion/Termination)
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Participants from the Full Analysis Set who provided at least data from baseline, Week 5 (or 10-15 EDs, whichever occurred last), Week 12 or Month 6
Arm/Group Title <6 Years Old 6 to <12 Years Old Full Analysis Set
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[Not Specified]
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 27 31 57
Mean (Standard Deviation)
Unit of Measure: IU/dL : IU/kg
Baseline [n=15, 16, 31] 1.6889  (0.27610) 1.7843  (0.35942) 1.7381  (0.32017)
Week 5 (or after 10-15 EDs) [n= 27, 30, 57] 1.8952  (0.55483) 1.8661  (0.49785) 1.8799  (0.52105)
Week 12 [n= 26, 31, 57] 1.6818  (0.23069) 1.9212  (0.42496) 1.8120  (0.36738)
Month 6 (Termination/Completion) [n=27, 28, 55] 1.5801  (0.31568) 1.7120  (0.36588) 1.6472  (0.34546)
23.Secondary Outcome
Title Pharmacokinetics (PK): Incremental Recovery (IR) of BAX 855 Over Time - Chromogenic Assay
Hide Description

Pre- and post-infusion levels of Factor VIII (FVIII) following infusion of BAX 855 were used to determine IR.

For participants who underwent PK evaluation, baseline IR was determined from the IR measurement used in the PK analysis. Refer to data in Outcome measure 21- "Pharmacokinetics (PK): Incremental Recovery (IR)", for the category "Chromogenic assay - BAX 855"

For participants who did not undergo a PK evaluation, baseline IR was determined at the baseline visit prior to the prophylactic treatment phase and is included in this outcome measure.

Category title includes number of participants [n] < 6 yrs; ≥6 to <12 yrs and the Full Analysis Set, respectively.

Time Frame Baseline, Week 5 (or 10-15 Exposure Days [EDs], whichever occurs last), Week 12, and Month 6 (Completion/Termination)
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Participants from the Full Analysis Set who provided at least data from baseline, Week 5 (or 10-15 EDs, whichever occurred last), Week 12 or Month 6.
Arm/Group Title <6 Years Old 6 to <12 Years Old Full Analysis Set
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 27 31 57
Mean (Standard Deviation)
Unit of Measure: IU/dL : IU/kg
Baseline [n= 15; 16; 31] 1.7675  (0.34998) 1.9334  (0.30000) 1.8532  (0.33055)
Week 5 (or after 10-15 EDs) [n= 27; 30; 57] 1.9273  (0.32400) 1.9960  (0.39258) 1.9635  (0.36021)
Week 12 [n= 26; 31; 57] 1.8794  (0.24281) 1.9869  (0.42300) 1.9379  (0.35368)
Month 6 (Termination/Completion) [n= 27; 28; 55] 1.8359  (0.29188) 2.0659  (0.45723) 1.9530  (0.39876)
24.Post-Hoc Outcome
Title Pharmacokinetics (PK): Plasma Half-life Ratio of BAX 855 to ADVATE
Hide Description This is a descriptive summary of the ratio of plasma half-life in the same subject for BAX 855 compared to ADVATE based on the final covariate model (first observation tabulation).
Time Frame (1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4
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Hide Analysis Population Description
Pharmacokinetic (PK) Analysis Set
Arm/Group Title PK Analysis Set
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Participants who had been treated with at least 1 dose of ADVATE (60 ±5 IU/kg) and 1 dose of BAX 855 (60 ±5 IU/kg) in the pharmacokinetic (PK) part of the study (prior to prophylactic treatment) and had at least 1 PK concentration available for population PK and non-compartmental analysis.
Overall Number of Participants Analyzed 31
Mean (Full Range)
Unit of Measure: hours (hr)
One stage clotting assay
1.30
(0.944 to 2.000)
Chromogenic assay
1.50
(0.894 to 4.810)
Time Frame Throughout the study period of 1 year (8-10 months per participant)
Adverse Event Reporting Description AEs were continuously monitored but specifically discussed and reviewed at these time points: pre- and post-PK infusion, at the baseline visit, during prophylactic treatment at these visits: Week 5 (or 10-15 exposure days (EDs)), Week 12, Week 20 (by phone); at the study completion visit at Month 6 or after at least 50 EDs, whichever occurred last.
 
Arm/Group Title BAX 855 Safety Analysis Set ADVATE Received Before BAX 855
Hide Arm/Group Description Participants who received at least 1 dose of BAX 855. Participants who received at least 1 dose of ADVATE prior to receiving BAX 855 in the PK part of the study.
All-Cause Mortality
BAX 855 Safety Analysis Set ADVATE Received Before BAX 855
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
BAX 855 Safety Analysis Set ADVATE Received Before BAX 855
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/66 (4.55%)      0/31 (0.00%)    
Blood and lymphatic system disorders     
Febrile Neutropenia *  1/66 (1.52%)  1 0/31 (0.00%) 
Pancytopenia *  1/66 (1.52%)  1 0/31 (0.00%) 
Gastrointestinal disorders     
Abdominal Pain *  1/66 (1.52%)  1 0/31 (0.00%) 
Gastritis *  1/66 (1.52%)  1 0/31 (0.00%) 
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
BAX 855 Safety Analysis Set ADVATE Received Before BAX 855
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   30/66 (45.45%)      0/31 (0.00%)    
Gastrointestinal disorders     
Diarrhoea *  5/66 (7.58%)  5 0/31 (0.00%) 
Vomiting *  5/66 (7.58%)  6 0/31 (0.00%) 
General disorders     
Pyrexia *  13/66 (19.70%)  20 0/31 (0.00%) 
Infections and infestations     
Nasopharyngitis *  5/66 (7.58%)  5 0/31 (0.00%) 
Upper Respiratory Tract Infection *  9/66 (13.64%)  9 0/31 (0.00%) 
Nervous system disorders     
Headache *  5/66 (7.58%)  7 0/31 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Cough *  4/66 (6.06%)  8 0/31 (0.00%) 
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Baxalta's agreements with PIs may vary per requirements of individual PI, but contain common elements. For this study, results may not be published without prior written approval of Sponsor.
Results Point of Contact
Name/Title: Study Director
Organization: Shire
Phone: +1 866 842 5335
Responsible Party: Shire ( Baxalta now part of Shire )
ClinicalTrials.gov Identifier: NCT02210091     History of Changes
Other Study ID Numbers: 261202
2014-000742-30 ( EudraCT Number )
First Submitted: July 25, 2014
First Posted: August 6, 2014
Results First Submitted: December 2, 2016
Results First Posted: January 27, 2017
Last Update Posted: May 29, 2019