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An Open-label Safety and Efficacy Study of Recombinant FVIII in Patients With Severe Hemophilia A

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: NCT02172950
Recruitment Status : Completed
First Posted : June 24, 2014
Results First Posted : October 27, 2021
Last Update Posted : October 27, 2021
Sponsor:
Information provided by (Responsible Party):
CSL Behring

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Hemophilia A
Severe Hemophilia A
Intervention Biological: rVIII-SingleChain
Enrollment 246
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Previously Treated Patients (PTPs) Previously Untreated Patients (PUPs)
Hide Arm/Group Description

The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule for the subject based upon the subject's pharmacokinetic (PK) profile, rVIII-SingleChain PK data, previous FVIII treatment regimen, and bleeding phenotype, if available.

rVIII-SingleChain: Recombinant single-chain coagulation factor VIII

The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics.

rVIII-SingleChain: Recombinant single-chain coagulation factor VIII
Period Title: Overall Study
Started 222 24
Completed 197 19
Not Completed 25 5
Reason Not Completed
Physician Decision             3             3
Lack of Efficacy             1             0
Adverse Event             4             1
Withdrawal by Subject             10             0
Protocol Violation             1             0
Lost to Follow-up             1             0
Death             1             0
Patient traveling             1             0
Patient went to other country             1             0
Patient relocated overseas             1             1
Patient moving             1             0
Arm/Group Title Previously Treated Patients (PTPs) Previously Untreated Patients (PUPs) Total
Hide Arm/Group Description

The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule for the subject based upon the subject's pharmacokinetic (PK) profile, rVIII-SingleChain PK data, previous FVIII treatment regimen, and bleeding phenotype, if available.

rVIII-SingleChain: Recombinant single-chain coagulation factor VIII

The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics.

rVIII-SingleChain: Recombinant single-chain coagulation factor VIII

 Total of all reporting groups
Overall Number of Baseline Participants 222 24 246
Hide Baseline Analysis Population Description
Age was analyzed separately as PTPs and PUPs
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 222 participants 24 participants 246 participants
<=18 years
95
  42.8%
24
 100.0%
119
  48.4%
Between 18 and 65 years
126
  56.8%
0
   0.0%
126
  51.2%
>=65 years
1
   0.5%
0
   0.0%
1
   0.4%
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
PTPs Number Analyzed 222 participants 0 participants 222 participants
22.5  (14.55) 22.5  (14.55)
PUPs Number Analyzed 0 participants 24 participants 24 participants
1.4  (1.18) 1.4  (1.18)
[1]
Measure Analysis Population Description: Age was analyzed separately as PTPs and PUPs
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 222 participants 24 participants 246 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
Male
222
 100.0%
24
 100.0%
246
 100.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 222 participants 24 participants 246 participants
Hispanic or Latino
10
   4.5%
1
   4.2%
11
   4.5%
Not Hispanic or Latino
212
  95.5%
23
  95.8%
235
  95.5%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 222 participants 24 participants 246 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
50
  22.5%
2
   8.3%
52
  21.1%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
12
   5.4%
7
  29.2%
19
   7.7%
White
158
  71.2%
15
  62.5%
173
  70.3%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
2
   0.9%
0
   0.0%
2
   0.8%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Czechia Number Analyzed 222 participants 24 participants 246 participants
2 0 2
United States Number Analyzed 222 participants 24 participants 246 participants
21 1 22
Malaysia Number Analyzed 222 participants 24 participants 246 participants
13 2 15
Thailand Number Analyzed 222 participants 24 participants 246 participants
10 0 10
Portugal Number Analyzed 222 participants 24 participants 246 participants
2 3 5
Austria Number Analyzed 222 participants 24 participants 246 participants
6 0 6
Netherlands Number Analyzed 222 participants 24 participants 246 participants
9 3 12
Ireland Number Analyzed 222 participants 24 participants 246 participants
5 0 5
Poland Number Analyzed 222 participants 24 participants 246 participants
36 0 36
France Number Analyzed 222 participants 24 participants 246 participants
7 0 7
Romania Number Analyzed 222 participants 24 participants 246 participants
4 0 4
Hungary Number Analyzed 222 participants 24 participants 246 participants
2 0 2
Japan Number Analyzed 222 participants 24 participants 246 participants
7 0 7
Philippines Number Analyzed 222 participants 24 participants 246 participants
18 0 18
Ukraine Number Analyzed 222 participants 24 participants 246 participants
17 0 17
United Kingdom Number Analyzed 222 participants 24 participants 246 participants
1 0 1
Switzerland Number Analyzed 222 participants 24 participants 246 participants
1 0 1
Spain Number Analyzed 222 participants 24 participants 246 participants
6 0 6
Lebanon Number Analyzed 222 participants 24 participants 246 participants
9 3 12
Canada Number Analyzed 222 participants 24 participants 246 participants
1 0 1
Italy Number Analyzed 222 participants 24 participants 246 participants
5 4 9
South Africa Number Analyzed 222 participants 24 participants 246 participants
14 8 22
Georgia Number Analyzed 222 participants 24 participants 246 participants
5 0 5
Australia Number Analyzed 222 participants 24 participants 246 participants
11 0 11
Germany Number Analyzed 222 participants 24 participants 246 participants
10 0 10
1.Primary Outcome
Title Incidence of Inhibitor Formation to FVIII in Previously Treated Patients (PTPs) With 100 Exposure Days (EDs) to CSL627
Hide Description [Not Specified]
Time Frame At the closest visit after 100 EDs (up to 5 years).
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population (SP) - comprised all the Enrolled Population who received at least 1 dose of rVIII-SingleChain (CSL627) during the study for any reason.
Arm/Group Title CSL627: Previously Treated Patients (PTPs)
Hide Arm/Group Description:

The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule for the subject based upon the subject's pharmacokinetic (PK) profile, rVIII-SingleChain PK data, previous FVIII treatment regimen, and bleeding phenotype, if available.

rVIII-SingleChain: Recombinant single-chain coagulation factor VIII
Overall Number of Participants Analyzed 198
Measure Type: Number
Unit of Measure: percentage of paticipants
0
2.Primary Outcome
Title Number of Previously Untreated Patients (PUPs) With High-titer Inhibitor Formation to FVIII With at Least 50 EDs to CSL627
Hide Description High-titer inhibitor is defined as an inhibitor titer of ≥ 5 Bethesda units/mL.
Time Frame At the closest visit after 50 EDs (up to 5 years).
Hide Outcome Measure Data
Hide Analysis Population Description
SP
Arm/Group Title CSL627: Previously Untreated Patients (PUPs)
Hide Arm/Group Description:

The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics.

rVIII-SingleChain: Recombinant single-chain coagulation factor VIII
Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: participants
5
3.Primary Outcome
Title Percent Treatment Success for Major Bleeding Episodes in PUPs
Hide Description Percentage of major bleeding episodes treated successfully where treatment success for a bleeding episode is defined as a rating of "excellent" or "good" on the investigator's clinical assessment of hemostatic efficacy 4-point scale "excellent, good, moderate or poor/no response". Major bleeding episodes are defined as bleeding episodes for which a subject is required to seek treatment at the hemophilia center or that threatens the subject's life or loss of limb.
Time Frame Up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy population (EP) - comprised all subjects in the Safety Population who received at least 1 dose of rVIII-SingleChain (CSL627) for either routine prophylaxis treatment or on-demand treatment during the study. This endpoint was analyzed for PUPs only.
Arm/Group Title CSL627: Previously Untreated Patients (PUPs)
Hide Arm/Group Description:

The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics.

rVIII-SingleChain: Recombinant single-chain coagulation factor VIII
Overall Number of Participants Analyzed 23
Overall Number of Units Analyzed
Type of Units Analyzed: Major bleeds
 1
Measure Type: Number
Unit of Measure: percentage of treatment success
100
4.Primary Outcome
Title Annualized Spontaneous Bleeding Rate in PUPs
Hide Description The annualized spontaneous bleeding rate for PUPs taking prophylaxis and on-demand treatment regimens.
Time Frame Up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
EP. This endpoint was analyzed for PUPs only.
Arm/Group Title CSL627: Previously Untreated Patients (PUPs)
Hide Arm/Group Description:

The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics.

rVIII-SingleChain: Recombinant single-chain coagulation factor VIII
Overall Number of Participants Analyzed 23
Mean (Standard Deviation)
Unit of Measure: Number of Spontaneous bleeds per year
On-demand Number Analyzed 12 participants
1.9  (2.252)
Prophylaxis Number Analyzed 23 participants
4.04  (6.374)
5.Secondary Outcome
Title Percentage of Bleeding Episodes Treated Successfully in PTPs
Hide Description Percentage of bleeding episodes treated successfully where treatment success for a bleeding episode is defined as a rating of "excellent" or "good" on the investigator's clinical assessment of hemostatic efficacy 4-point scale "excellent, good, moderate or poor/no response".
Time Frame Up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
EP
Arm/Group Title CSL627: Previously Treated Patients (PTPs)
Hide Arm/Group Description:

The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule for the subject based upon the subject's pharmacokinetic (PK) profile, rVIII-SingleChain PK data, previous FVIII treatment regimen, and bleeding phenotype, if available.

rVIII-SingleChain: Recombinant single-chain coagulation factor VIII
Overall Number of Participants Analyzed 222
Overall Number of Units Analyzed
Type of Units Analyzed: Number of treated bleeding events
 2413
Measure Type: Number
Number (99% Confidence Interval)
Unit of Measure: Percentage of treated bleeding events
87.1
(75.3 to 93.7)
6.Secondary Outcome
Title Annualized Bleeding Rate in PTPs and PUPs
Hide Description The annualized bleeding rate for PTPs and PUPs taking prophylaxis and on-demand treatment regimens
Time Frame Up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
EP
Arm/Group Title CSL627: Previously Treated Patients (PTPs) CSL627: Previously Untreated Patients (PUPs)
Hide Arm/Group Description:

The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule for the subject based upon the subject's pharmacokinetic (PK) profile, rVIII-SingleChain PK data, previous FVIII treatment regimen, and bleeding phenotype, if available.

rVIII-SingleChain: Recombinant single-chain coagulation factor VIII

The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics.

rVIII-SingleChain: Recombinant single-chain coagulation factor VIII
Overall Number of Participants Analyzed 222 23
Mean (Standard Deviation)
Unit of Measure: Number of bleeds per year
On-demand Number Analyzed 11 participants 10 participants
28.32  (29.014) 5.12  (5.331)
Prophylaxis Number Analyzed 209 participants 23 participants
2.84  (4.981) 5.94  (7.705)
7.Secondary Outcome
Title Percentage of Bleeding Episodes Requiring 1, 2, 3, or > 3 Injections of CSL627 to Achieve Hemostasis in PTPs and PUPs
Hide Description [Not Specified]
Time Frame Up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
EP
Arm/Group Title CSL627: Previously Treated Patients (PTPs) CSL627: Previously Untreated Patients (PUPs)
Hide Arm/Group Description:

The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule for the subject based upon the subject's pharmacokinetic (PK) profile, rVIII-SingleChain PK data, previous FVIII treatment regimen, and bleeding phenotype, if available.

rVIII-SingleChain: Recombinant single-chain coagulation factor VIII

The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics.

rVIII-SingleChain: Recombinant single-chain coagulation factor VIII
Overall Number of Participants Analyzed 222 24
Overall Number of Units Analyzed
Type of Units Analyzed: Treated bleeds
 2413 315
Measure Type: Number
Unit of Measure: Percentage of treated bleeds
1 infusion 71.5 77.5
2 infusions 14.8 11.4
3 infusions 6.9 5.4
>3 infusions 6.3 3.5
8.Secondary Outcome
Title Mean Number of On-demand Infusions of CSL627
Hide Description [Not Specified]
Time Frame Up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
EP. This endpoint analyzes PTPs and PUPs that received on-demand treatment.
Arm/Group Title CSL627: Previously Treated Patients (PTPs) CSL627: Previously Untreated Patients (PUPs)
Hide Arm/Group Description:

The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule for the subject based upon the subject's pharmacokinetic (PK) profile, rVIII-SingleChain PK data, previous FVIII treatment regimen, and bleeding phenotype, if available.

rVIII-SingleChain: Recombinant single-chain coagulation factor VIII

The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics.

rVIII-SingleChain: Recombinant single-chain coagulation factor VIII
Overall Number of Participants Analyzed 11 12
Mean (Standard Deviation)
Unit of Measure: Number of infusions
per participant per month 6.26  (4.778) 1.23  (1.296)
per participant per year 75.18  (57.335) 14.75  (15.547)
9.Secondary Outcome
Title Mean On-demand Dose Administered of CSL627
Hide Description [Not Specified]
Time Frame Up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
EP. This endpoint analyzes PTPs and PUPs that received on-demand treatment.
Arm/Group Title CSL627: Previously Treated Patients (PTPs) CSL627: Previously Untreated Patients (PUPs)
Hide Arm/Group Description:

The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule for the subject based upon the subject's pharmacokinetic (PK) profile, rVIII-SingleChain PK data, previous FVIII treatment regimen, and bleeding phenotype, if available.

rVIII-SingleChain: Recombinant single-chain coagulation factor VIII

The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics.

rVIII-SingleChain: Recombinant single-chain coagulation factor VIII
Overall Number of Participants Analyzed 11 12
Mean (Standard Deviation)
Unit of Measure: IU/kg
per participant per month 210.39  (188.106) 41.93  (44.643)
per participant per year 2524.69  (2257.278) 503.16  (535.712)
10.Secondary Outcome
Title Mean Prophylaxis Dose Administered of CSL627
Hide Description [Not Specified]
Time Frame Up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
EP. This endpoint analyzes PTPs and PUPs that received prophylaxis treatment.
Arm/Group Title CSL627: Previously Treated Patients (PTPs) CSL627: Previously Untreated Patients (PUPs)
Hide Arm/Group Description:

The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule for the subject based upon the subject's pharmacokinetic (PK) profile, rVIII-SingleChain PK data, previous FVIII treatment regimen, and bleeding phenotype, if available.

rVIII-SingleChain: Recombinant single-chain coagulation factor VIII

The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics.

rVIII-SingleChain: Recombinant single-chain coagulation factor VIII
Overall Number of Participants Analyzed 211 23
Mean (Standard Deviation)
Unit of Measure: IU/kg
per participant per month 380.95  (130.079) 389.30  (243.191)
per participant per year 4571.35  (1560.944) 4671.54  (2918.288)
11.Secondary Outcome
Title Mean Total Amount of CSL627 Administered During Surgery Period in PTPs
Hide Description [Not Specified]
Time Frame Day of surgery up to 336 hours post-surgery
Hide Outcome Measure Data
Hide Analysis Population Description
Surgery population
Arm/Group Title CSL627: Previously Treated Patients (PTPs)
Hide Arm/Group Description:

The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule for the subject based upon the subject's pharmacokinetic (PK) profile, rVIII-SingleChain PK data, previous FVIII treatment regimen, and bleeding phenotype, if available.

rVIII-SingleChain: Recombinant single-chain coagulation factor VIII
Overall Number of Participants Analyzed 24
Mean (Standard Deviation)
Unit of Measure: IU
51663.0  (62033.25)
12.Secondary Outcome
Title Total Amount of CSL627 Administered During Surgery Period in PUPs
Hide Description [Not Specified]
Time Frame Day of surgery up to 336 hours post-surgery
Hide Outcome Measure Data
Hide Analysis Population Description
Surgery population
Arm/Group Title CSL627: Previously Untreated Patients (PUPs)
Hide Arm/Group Description:

The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics.

rVIII-SingleChain: Recombinant single-chain coagulation factor VIII
Overall Number of Participants Analyzed 3
Measure Type: Number
Unit of Measure: IU
Participant 1 15693
Participant 2 5631
Participant 3 7330
13.Secondary Outcome
Title Hemostatic Efficacy of rVIII-SingleChain for PTPs and PUPs Who Undergo Surgery
Hide Description The investigator will rate the efficacy of the rVIII-SingleChain treatment during surgery based on a hemostatic efficacy four point rating scale of "excellent, good, moderate or poor/no response".
Time Frame From the start of surgery through the post-operative recovery (generally up to 14 days after surgery)
Hide Outcome Measure Data
Hide Analysis Population Description
Surgery population - comprised all subjects in the Safety Population who received at least 1 dose of rVIII-SingleChain for surgical prophylaxis
Arm/Group Title CSL627: Previously Treated Patients (PTPs) CSL627: Previously Untreated Patients (PUPs)
Hide Arm/Group Description:

The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule for the subject based upon the subject's pharmacokinetic (PK) profile, rVIII-SingleChain PK data, previous FVIII treatment regimen, and bleeding phenotype, if available.

rVIII-SingleChain: Recombinant single-chain coagulation factor VIII

The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics.

rVIII-SingleChain: Recombinant single-chain coagulation factor VIII
Overall Number of Participants Analyzed 24 3
Overall Number of Units Analyzed
Type of Units Analyzed: Surgeries
 32 3
Measure Type: Number
Unit of Measure: Number of surgeries
Excellent 28 3
Good 4 0
Moderate 0 0
Poor/No response 0 0
14.Secondary Outcome
Title Incidence of Inhibitor Formation to FVIII in PTPs After 10 EDs and After 50 EDs
Hide Description [Not Specified]
Time Frame Up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
SP
Arm/Group Title CSL627: Previously Treated Patients (PTPs)
Hide Arm/Group Description:

The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule for the subject based upon the subject's pharmacokinetic (PK) profile, rVIII-SingleChain PK data, previous FVIII treatment regimen, and bleeding phenotype, if available.

rVIII-SingleChain: Recombinant single-chain coagulation factor VIII
Overall Number of Participants Analyzed 198
Measure Type: Number
Unit of Measure: percentage of participants
after 10 EDs 0
after 50 EDs 0
15.Secondary Outcome
Title Percentage of PTPs and PUPs Developing Antibodies Against CSL627
Hide Description [Not Specified]
Time Frame PTPs: At the closest visit after 100 EDs (up to 5 years). PUPs: At the closest visit after 50 EDs (up to 5 years).
Hide Outcome Measure Data
Hide Analysis Population Description
SP
Arm/Group Title CSL627: Previously Treated Patients (PTPs) CSL627: Previously Untreated Patients (PUPs)
Hide Arm/Group Description:

The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule for the subject based upon the subject's pharmacokinetic (PK) profile, rVIII-SingleChain PK data, previous FVIII treatment regimen, and bleeding phenotype, if available.

rVIII-SingleChain: Recombinant single-chain coagulation factor VIII

The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics.

rVIII-SingleChain: Recombinant single-chain coagulation factor VIII
Overall Number of Participants Analyzed 222 24
Measure Type: Number
Unit of Measure: percentage of participants
15.3 70.8
16.Secondary Outcome
Title Percentage of PTPs and PUPs Developing Antibodies to Chinese Hamster Ovary (CHO) Proteins
Hide Description [Not Specified]
Time Frame PTPs: At the closest visit after 100 EDs (up to 5 years). PUPs: At the closest visit after 50 EDs (up to 5 years).
Hide Outcome Measure Data
Hide Analysis Population Description
SP
Arm/Group Title CSL627: Previously Treated Patients (PTPs) CSL627: Previously Untreated Patients (PUPs)
Hide Arm/Group Description:

The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule for the subject based upon the subject's pharmacokinetic (PK) profile, rVIII-SingleChain PK data, previous FVIII treatment regimen, and bleeding phenotype, if available.

rVIII-SingleChain: Recombinant single-chain coagulation factor VIII

The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics.

rVIII-SingleChain: Recombinant single-chain coagulation factor VIII
Overall Number of Participants Analyzed 222 24
Measure Type: Number
Unit of Measure: percentage of participants
0 0
17.Secondary Outcome
Title Number of PUPs With High-titer Inhibitor Formation to FVIII After 10 EDs With CSL627
Hide Description High-titer inhibitor is defined as an inhibitor titer of ≥ 5 Bethesda units/mL.
Time Frame At the closest visit after 10 EDs (up to 5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
SP
Arm/Group Title CSL627: Previously Untreated Patients (PUPs)
Hide Arm/Group Description:

The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics.

rVIII-SingleChain: Recombinant single-chain coagulation factor VIII
Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: participants
4
18.Secondary Outcome
Title Number of PUPs With Low-titer Inhibitor Formation to FVIII After 10 EDs and After 50 EDs With CSL627
Hide Description Low-titer inhibitor is defined as an inhibitor titer of less than 5 Bethesda units/mL.
Time Frame At the closest visit after 10 and after 50 EDs (up to 5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
SP
Arm/Group Title CSL627: Previously Untreated Patients (PUPs)
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The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics.

rVIII-SingleChain: Recombinant single-chain coagulation factor VIII
Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: participants
after 10 EDs 4
after 50 EDs 0
19.Secondary Outcome
Title Incidence of Total Inhibitor Formation to FVIII in PUPs
Hide Description [Not Specified]
Time Frame Up to 5 years
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SP
Arm/Group Title CSL627: Previously Untreated Patients (PUPs)
Hide Arm/Group Description:

The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics.

rVIII-SingleChain: Recombinant single-chain coagulation factor VIII
Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: percentage of participants
50.0
20.Secondary Outcome
Title Percent Treatment Success for Non-major Bleeding Episodes in PUPs
Hide Description Percentage of bleeding episodes treated successfully where treatment success for a bleeding episode is defined as a rating of "excellent" or "good" on the investigator's clinical assessment of hemostatic efficacy 4-point scale "excellent, good, moderate or poor/no response". Non-major bleeding episodes are those not requiring treatment at the hemophilia center or not threatening subject's life or loss of limb.
Time Frame Up to 5 years
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EP. This endpoint was analyzed for PUPs only.
Arm/Group Title CSL627: Previously Untreated Patients (PUPs)
Hide Arm/Group Description:

The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics.

rVIII-SingleChain: Recombinant single-chain coagulation factor VIII
Overall Number of Participants Analyzed 24
Overall Number of Units Analyzed
Type of Units Analyzed: Treated bleeding events
 315
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of treated bleeding events
92.1
(87.0 to 95.3)
21.Secondary Outcome
Title Percentage of PUPs With Clinically Significant Abnormal Vital Signs Values After First Infusion of CSL627
Hide Description Vital signs assessments include heart rate, blood pressure, and body temperature. Clinical significance of an abnormality will be assessed by the investigator.
Time Frame Up to 6 hours after first infusion
Hide Outcome Measure Data
Hide Analysis Population Description
SP. This endpoint was analyzed for PUPs only.
Arm/Group Title CSL627: Previously Untreated Patients (PUPs)
Hide Arm/Group Description:

The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics.

rVIII-SingleChain: Recombinant single-chain coagulation factor VIII
Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: percentage of participants
0
22.Secondary Outcome
Title Percentage of PUPs With Treatment-emergent Clinically Significant Abnormal Vital Signs Values
Hide Description Vital signs assessments include heart rate, blood pressure, and body temperature. Clinical significance of an abnormality will be assessed by the investigator.
Time Frame Up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
SP. This endpoint was analyzed for PUPs only.
Arm/Group Title CSL627: Previously Untreated Patients (PUPs)
Hide Arm/Group Description:

The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics.

rVIII-SingleChain: Recombinant single-chain coagulation factor VIII
Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: percentage of participants
0
Time Frame Up to 5 years
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title CSL627: Previously Treated Patients (PTPs) CSL627: Previously Untreated Patients (PUPs)
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The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule for the subject based upon the subject's pharmacokinetic (PK) profile, rVIII-SingleChain PK data, previous FVIII treatment regimen, and bleeding phenotype, if available.

rVIII-SingleChain: Recombinant single-chain coagulation factor VIII

The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII-SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics.

rVIII-SingleChain: Recombinant single-chain coagulation factor VIII
All-Cause Mortality
CSL627: Previously Treated Patients (PTPs) CSL627: Previously Untreated Patients (PUPs)
Affected / at Risk (%) Affected / at Risk (%)
Total   1/222 (0.45%)      0/24 (0.00%)    
Hide Serious Adverse Events
CSL627: Previously Treated Patients (PTPs) CSL627: Previously Untreated Patients (PUPs)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   23/222 (10.36%)      14/24 (58.33%)    
Blood and lymphatic system disorders     
Factor VIII inhibition † 1  0/222 (0.00%)  0 1/24 (4.17%)  1
Eye disorders     
Blindness transient † 1  1/222 (0.45%)  1 0/24 (0.00%)  0
Gastrointestinal disorders     
Diarrhoea † 1  1/222 (0.45%)  1 0/24 (0.00%)  0
Duodenal ulcer † 1  1/222 (0.45%)  1 0/24 (0.00%)  0
Gastritis erosive † 1  1/222 (0.45%)  1 0/24 (0.00%)  0
Gastrointestinal haemorrhage † 1  1/222 (0.45%)  1 0/24 (0.00%)  0
Haemorrhoids † 1  1/222 (0.45%)  1 0/24 (0.00%)  0
Mouth haemorrhage † 1  0/222 (0.00%)  0 1/24 (4.17%)  1
General disorders     
Chest pain † 1  1/222 (0.45%)  1 0/24 (0.00%)  0
Infections and infestations     
Appendicitis † 1  2/222 (0.90%)  2 0/24 (0.00%)  0
Cellulitis † 1  1/222 (0.45%)  1 0/24 (0.00%)  0
Lower respiratory tract infection † 1  1/222 (0.45%)  1 0/24 (0.00%)  0
Pneumonia † 1  1/222 (0.45%)  1 0/24 (0.00%)  0
Wound infection † 1  1/222 (0.45%)  1 0/24 (0.00%)  0
Device related infection † 1  0/222 (0.00%)  0 1/24 (4.17%)  1
Acinetobacter infection † 1  0/222 (0.00%)  0 1/24 (4.17%)  1
Influenza † 1  1/222 (0.45%)  1 0/24 (0.00%)  0
Injury, poisoning and procedural complications     
Road traffic accident † 1  2/222 (0.90%)  2 0/24 (0.00%)  0
Abdominal injury † 1  1/222 (0.45%)  1 0/24 (0.00%)  0
Periprosthetic fracture † 1  1/222 (0.45%)  1 0/24 (0.00%)  0
Skin laceration † 1  1/222 (0.45%)  1 0/24 (0.00%)  0
Fall † 1  0/222 (0.00%)  0 2/24 (8.33%)  2
Wound haemorrhage † 1  0/222 (0.00%)  0 1/24 (4.17%)  1
Investigations     
Anti factor VIII antibody positive † 1  0/222 (0.00%)  0 6/24 (25.00%)  6
Inhibiting antibodies positive † 1  0/222 (0.00%)  0 5/24 (20.83%)  5
Musculoskeletal and connective tissue disorders     
Haemophilic arthropathy † 1  3/222 (1.35%)  3 0/24 (0.00%)  0
Muscle haemorrhage † 1  1/222 (0.45%)  1 0/24 (0.00%)  0
Musculoskeletal stiffness † 1  1/222 (0.45%)  1 0/24 (0.00%)  0
Tendinous contracture † 1  1/222 (0.45%)  1 0/24 (0.00%)  0
Muscle spasms † 1  0/222 (0.00%)  0 1/24 (4.17%)  1
Nervous system disorders     
Generalised tonic-clonic seizure † 1  1/222 (0.45%)  1 0/24 (0.00%)  0
Lennox-Gastaut syndrome † 1  1/222 (0.45%)  1 0/24 (0.00%)  0
Seizure † 1  1/222 (0.45%)  1 0/24 (0.00%)  0
Renal and urinary disorders     
Nephritis † 1  1/222 (0.45%)  1 0/24 (0.00%)  0
Social circumstances     
Pregnancy of partner † 1  1/222 (0.45%)  1 0/24 (0.00%)  0
Vascular disorders     
Shock † 1  1/222 (0.45%)  1 0/24 (0.00%)  0
Vasospasm † 1  1/222 (0.45%)  1 0/24 (0.00%)  0
Haemorrhage † 1  0/222 (0.00%)  0 1/24 (4.17%)  1
1
Term from vocabulary, MedDRA 21.1
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
CSL627: Previously Treated Patients (PTPs) CSL627: Previously Untreated Patients (PUPs)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   130/222 (58.56%)      23/24 (95.83%)    
Blood and lymphatic system disorders     
Iron deficiency anaemia † 1  2/222 (0.90%)  3 3/24 (12.50%)  3
Ear and labyrinth disorders     
Ear pain † 1  4/222 (1.80%)  4 2/24 (8.33%)  2
Gastrointestinal disorders     
Dental caries † 1  11/222 (4.95%)  11 0/24 (0.00%)  0
Diarrhoea † 1  5/222 (2.25%)  5 5/24 (20.83%)  6
Vomiting † 1  4/222 (1.80%)  5 3/24 (12.50%)  8
General disorders     
Pyrexia † 1  14/222 (6.31%)  18 15/24 (62.50%)  44
Malaise † 1  0/222 (0.00%)  0 2/24 (8.33%)  4
Immune system disorders     
Allergy to arthropod sting † 1  0/222 (0.00%)  0 2/24 (8.33%)  5
Infections and infestations     
Nasopharyngitis † 1  40/222 (18.02%)  73 9/24 (37.50%)  15
Upper respiratory tract infection † 1  25/222 (11.26%)  37 7/24 (29.17%)  18
Influenza † 1  14/222 (6.31%)  16 4/24 (16.67%)  6
Tonsillitis † 1  13/222 (5.86%)  17 5/24 (20.83%)  5
Rhinitis † 1  7/222 (3.15%)  7 6/24 (25.00%)  10
Ear infection † 1  5/222 (2.25%)  8 5/24 (20.83%)  9
Conjunctivitis † 1  6/222 (2.70%)  6 3/24 (12.50%)  4
Bronchitis † 1  5/222 (2.25%)  7 3/24 (12.50%)  3
Varicella † 1  2/222 (0.90%)  2 6/24 (25.00%)  7
Otitis media † 1  3/222 (1.35%)  5 4/24 (16.67%)  5
Viral rhinitis † 1  1/222 (0.45%)  1 2/24 (8.33%)  2
Scarlet fever † 1  0/222 (0.00%)  0 2/24 (8.33%)  2
Tinea capitis † 1  0/222 (0.00%)  0 2/24 (8.33%)  2
Injury, poisoning and procedural complications     
Fall † 1  11/222 (4.95%)  12 3/24 (12.50%)  5
Head injury † 1  11/222 (4.95%)  11 1/24 (4.17%)  3
Contusion † 1  11/222 (4.95%)  13 0/24 (0.00%)  0
Investigations     
Coronavirus test positive † 1  0/222 (0.00%)  0 2/24 (8.33%)  2
Inhibiting antibodies positive † 1  0/222 (0.00%)  0 2/24 (8.33%)  2
Musculoskeletal and connective tissue disorders     
Arthralgia † 1  20/222 (9.01%)  28 1/24 (4.17%)  1
Joint swelling † 1  4/222 (1.80%)  5 2/24 (8.33%)  2
Haemarthrosis † 1  2/222 (0.90%)  3 2/24 (8.33%)  2
Nervous system disorders     
Headache † 1  20/222 (9.01%)  29 0/24 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Cough † 1  13/222 (5.86%)  19 6/24 (25.00%)  13
Rhinorrhoea † 1  3/222 (1.35%)  3 2/24 (8.33%)  3
Bronchospasm † 1  0/222 (0.00%)  0 2/24 (8.33%)  4
Skin and subcutaneous tissue disorders     
Rash † 1  6/222 (2.70%)  6 3/24 (12.50%)  3
Eczema † 1  1/222 (0.45%)  1 3/24 (12.50%)  3
Vascular disorders     
Haematoma † 1  2/222 (0.90%)  2 2/24 (8.33%)  3
1
Term from vocabulary, MedDRA 21.1
†
Indicates events were collected by systematic assessment
[Not Specified]
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.
CSL agreements and restrictions on publishing may vary with individual investigators; however, CSL will not prohibit any investigator from publishing. CSL supports the publication of results from all centers of a multi-center trial and generally requires that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Clinical Trial Disclosure Manager
Organization: CSL Behring
Phone: use email contact
EMail: clinicaltrials@cslbehring.com
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Responsible Party: CSL Behring
ClinicalTrials.gov Identifier: NCT02172950    
Other Study ID Numbers: CSL627_3001
2013-003262-13 ( EudraCT Number )
First Submitted: June 23, 2014
First Posted: June 24, 2014
Results First Submitted: August 30, 2021
Results First Posted: October 27, 2021
Last Update Posted: October 27, 2021