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An Open-label Safety, Efficacy and Pharmacokinetic Study of a Recombinant FVIII Compared to Recombinant Human Antihemophilic 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: NCT01486927
Recruitment Status : Completed
First Posted : December 7, 2011
Results First Posted : August 9, 2016
Last Update Posted : August 9, 2016
Sponsor:
Information provided by (Responsible Party):
CSL Behring

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hemophilia A
Interventions Biological: rVIII-SingleChain
Biological: Octocog alfa
Enrollment 175
Recruitment Details This multicenter, multinational study enrolled subjects at 54 participating study centers in the United States, Japan, Europe, Australia, Canada, Lebanon, Malaysia, Philippines, Russian Federation, South Africa, and Ukraine.
Pre-assignment Details Screening took place 4 to 28 days prior to first dose of study product (rVIII-SingleChain). A total of 204 subjects were screened, 29 of these did not fulfill all eligibility criteria and were therefore screening failures. A total of 175 subjects were enrolled; 174 subjects were exposed to treatment with rVIII-SingleChain.
Arm/Group Title Recombinant Factor VIII (rFVIII)
Hide Arm/Group Description In Part 1 of the study (a single-sequence crossover pharmacokinetic [PK] analysis), 27 subjects received a single injection of octocog alfa followed by a single injection of rVIII-SingleChain. Twenty-six of the 27 subjects from Part 1 then entered Part 2 of the study where they were assigned either to an on-demand or prophylaxis regimen with repeat injections of rVIII-SingleChain until they reached 50 exposure days (EDs). In Part 3 of the study, 148 additional subjects were enrolled and were assigned either to an on-demand or prophylaxis regimen with repeat injections of rVIII-SingleChain until they reached 50 EDs; 64 of these subjects participated in additional PK analyses. Overall, 174 subjects received rVIII-SingleChain as either on-demand or prophylaxis regimens, and 13 subjects participated in the surgical substudy.
Period Title: Overall Study
Started 174
Completed 161
Not Completed 13
Reason Not Completed
Knee surgery (prior to surgery substudy)             1
Physician Decision             1
50 Exposure days not reached             2
Withdrawal by Subject             8
Subject did not reach 6 mo of treatment             1
Arm/Group Title Recombinant Factor VIII (rFVIII)
Hide Arm/Group Description In Part 1 of the study (a single-sequence crossover PK analysis), 27 subjects received a single injection of octocog alfa followed by a single injection of rVIII-SingleChain. Twenty-six of the 27 subjects from Part 1 then entered Part 2 of the study where they were assigned either to an on-demand or prophylaxis regimen with repeat injections of rVIII-SingleChain until they reached 50 EDs. In Part 3 of the study, 148 additional subjects were enrolled and were assigned either to an on-demand or prophylaxis regimen with repeat injections of rVIII-SingleChain until they reached 50 EDs; 64 of these subjects participated in additional PK analyses. Overall, 174 subjects received rVIII-SingleChain as either on-demand or prophylaxis regimens, and 13 subjects participated in the surgical substudy.
Overall Number of Baseline Participants 174
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 174 participants
31.3  (11.77)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 174 participants
Adolescents (12-17 years) 14
Adults (18-65 years) 160
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 174 participants
Female
0
   0.0%
Male
174
 100.0%
Type of FVIII product used before enrollment   [1] 
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 174 participants
Plasma-derived Product 83
Recombinant Product 91
[1]
Measure Description: Type of FVIII product used by the subjects before enrollment into the study. This could have been a plasma-derived FVIII product or a recombinant FVIII product.
Treatment modality of FVIII therapy before enrollment   [1] 
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 174 participants
Prophylaxis 82
On-demand 92
[1]
Measure Description: Treatment modality of FVIII therapy before enrollment, ie, routine prophylaxis or on-demand treatment. If a subject used both modalities, only the most recent one was counted.
1.Primary Outcome
Title Treatment Success
Hide Description The investigator rated the efficacy of the treatment based on a 4-point rating scale "excellent, good, moderate or poor/no response". Efficacy ratings of "excellent" or "good" were considered treatment success for this end point; the percentage of bleeding events with a rating of excellent or good and the 95% confidence interval are presented. The denominator includes all treated bleeding events. The 95% confidence interval is based on a model to account for within-subject correlation.
Time Frame Up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title rVIII-SingleChain On-demand rVIII-SingleChain Prophylaxis rVIII-SingleChain
Hide Arm/Group Description:
The rVIII-SingleChain On-demand group consisted of all subjects in the efficacy population who received at least 1 dose rVIII-SingleChain as part of on-demand treatment during Parts 2 or 3 of the study. There were 27 subjects in the rVIII-SingleChain On-demand group.
The rVIII-SingleChain Prophylaxis group consisted of all subjects in the efficacy population who received at least 1 dose rVIII-SingleChain as part of routine prophylaxis treatment during Parts 2 or 3 of the study. There were 146 subjects in the rVIII-SingleChain Prophylaxis group.
The Efficacy population consisted of all subjects who received at least 1 dose of rVIII-SingleChain as part of either routine prophylaxis treatment or on-demand treatment during Parts 2 or 3 of the study. There were 173 subjects in the Efficacy population.
Overall Number of Participants Analyzed 27 146 173
Overall Number of Units Analyzed
Type of Units Analyzed: Number of treated bleeding events
 590 258 848
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: % bleeding events successfully treated
92.4
(87.8 to 95.3)
92.2
(86.3 to 95.8)
92.3
(88.9 to 94.8)
2.Primary Outcome
Title Inhibitor Formation to FVIII
Hide Description Number of subjects who develop inhibitors to FVIII
Time Frame Up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Recombinant Factor VIII (rFVIII)
Hide Arm/Group Description:
In Part 1 of the study (a single-sequence crossover PK analysis), 27 subjects received a single injection of octocog alfa followed by a single injection of rVIII-SingleChain. Twenty-six of the 27 subjects from Part 1 then entered Part 2 of the study where they were assigned either to an on-demand or prophylaxis regimen with repeat injections of rVIII-SingleChain until they reached 50 EDs. In Part 3 of the study, 148 additional subjects were enrolled and were assigned either to an on-demand or prophylaxis regimen with repeat injections of rVIII-SingleChain until they reached 50 EDs; 64 of these subjects participated in additional PK analyses. Overall, 174 subjects received rVIII-SingleChain as either on-demand or prophylaxis regimens, and 13 subjects participated in the surgical substudy.
Overall Number of Participants Analyzed 174
Measure Type: Number
Unit of Measure: participants
0
3.Primary Outcome
Title Annualized Spontaneous Bleeding Rate
Hide Description The annualized spontaneous bleeding rate (AsBR) was derived for each subject as follows: 365.25*(number of spontaneous bleeding episodes requiring treatment) / (observed treatment period of interest).
Time Frame Up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title rVIII-SingleChain On-demand rVIII-SingleChain Prophylaxis
Hide Arm/Group Description:
The rVIII-SingleChain On-demand group consisted of all subjects in the efficacy population who received at least 1 dose rVIII-SingleChain as part of on-demand treatment during Parts 2 or 3 of the study. There were 27 subjects in the rVIII-SingleChain On-demand group.
The rVIII-SingleChain Prophylaxis group consisted of all subjects in the efficacy population who received at least 1 dose rVIII-SingleChain as part of routine prophylaxis treatment during Parts 2 or 3 of the study. There were 146 subjects in the rVIII-SingleChain Prophylaxis group.
Overall Number of Participants Analyzed 27 146
Median (Inter-Quartile Range)
Unit of Measure: Number of spontaneous bleeds per year
11.73
(2.8 to 36.5)
0.00
(0.0 to 2.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection rVIII-SingleChain On-demand, rVIII-SingleChain Prophylaxis
Comments A test of the null hypothesis of no difference on AsBR between the 2 comparison groups was based on the Poisson Regression method. The corresponding prophylaxis/on-demand ratio with 95% confidence interval (CI) was calculated.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Poisson, regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate ratio
Estimated Value 0.08
Confidence Interval (2-Sided) 95%
0.07 to 0.10
Estimation Comments [Not Specified]
4.Primary Outcome
Title Treatment Success During the Peri-operative Surgical Sub-study
Hide Description Subjects received rVIII-SingleChain before and during surgery based on the type of surgery and the clinical status of the subject. The investigator rated the efficacy of the treatment based on a 4-point surgical treatment rating scale of "excellent, good, moderate or poor/no response". Efficacy ratings of "excellent" or "good" were considered treatment success for this end point. The rate of success, defined as the percentage of surgeries with a rating of excellent or good for hemostatic efficacy on the surgical treatment scale is presented for the Surgical Population, based on the total number of surgeries (N=16) as denominator.
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
[Not Specified]
Arm/Group Title rVIII-SingleChain Surgical
Hide Arm/Group Description:
The rVIII-SingleChain Surgical group included all subjects enrolled in the surgical sub-study who received at least 1 dose of rVIII-SingleChain during the surgical sub-study. There were 13 subjects in the rVIII-SingleChain Surgical group.
Overall Number of Participants Analyzed 13
Measure Type: Number
Unit of Measure: % of surgeries with successful treatment
100
5.Secondary Outcome
Title AUC0-∞ (Part 1)
Hide Description AUC0-∞ (AUC from 0 extrapolated to infinity) of a single infusion of octocog alfa and rVIII-SingleChain without correction for subject's predose plasma FVIII activity. FVIII activity values for octocog alfa are dose-adjusted for chromogenic potency.
Time Frame Before infusion and at up to 10 time points within 72 hours of infusion
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK Population (Part 1)
Hide Arm/Group Description:
The PK population (Part 1) consisted of subjects who had received 1 dose of 50 IU/kg of rVIII-SingleChain and for whom a sufficient number of analyzable PK samples were obtained to permit the evaluation of the PK profile. In the Part 1 PK analysis, these subjects also received 1 dose of 50 IU/kg octocog alfa. There were 27 subjects in the PK population (Part 1).
Overall Number of Participants Analyzed 27
Mean (Standard Deviation)
Unit of Measure: IU*h/dL
Octocog alfa 1550  (552)
rVIII-SingleChain 2090  (650)
6.Secondary Outcome
Title Cmax (Part 1)
Hide Description Cmax of a single infusion of octocog alfa and rVIII-SingleChain with correction for subject's predose plasma FVIII activity. FVIII activity values for octocog alfa are dose-adjusted for chromogenic potency.
Time Frame Before infusion and at up to 10 time points within 72 hours of infusion
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK Population (Part 1)
Hide Arm/Group Description:
The PK population (Part 1) consisted of subjects who had received 1 dose of 50 IU/kg of rVIII-SingleChain and for whom a sufficient number of analyzable PK samples were obtained to permit the evaluation of the PK profile. In the Part 1 PK analysis, these subjects also received 1 dose of 50 IU/kg octocog alfa. There were 27 subjects in the PK population (Part 1).
Overall Number of Participants Analyzed 27
Mean (Standard Deviation)
Unit of Measure: IU/dL
Octocog alfa 116  (18.1)
rVIII-SingleChain 113  (17.4)
7.Secondary Outcome
Title Tmax (Part 1)
Hide Description Tmax = time of Cmax (with correction for subject's predose plasma FVIII activity) after a single infusion of octocog alfa and rVIII-SingleChain.
Time Frame Before infusion and at up to 10 time points within 72 hours of infusion
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK Population (Part 1)
Hide Arm/Group Description:
The PK population (Part 1) consisted of subjects who had received 1 dose of 50 IU/kg of rVIII-SingleChain and for whom a sufficient number of analyzable PK samples were obtained to permit the evaluation of the PK profile. In the Part 1 PK analysis, these subjects also received 1 dose of 50 IU/kg octocog alfa. There were 27 subjects in the PK population (Part 1).
Overall Number of Participants Analyzed 27
Median (Full Range)
Unit of Measure: hours
Octocog alfa
0.583
(0.450 to 0.800)
rVIII-SingleChain
0.683
(0.467 to 1.25)
8.Secondary Outcome
Title Half-life (t1/2) (Part 1)
Hide Description Half-life (t1/2) of a single infusion of octocog alfa and rVIII-SingleChain without correction for subject's predose plasma FVIII activity.
Time Frame Before infusion and at up to 10 time points within 72 hours of infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK Population (Part 1)
Hide Arm/Group Description:
The PK population (Part 1) consisted of subjects who had received 1 dose of 50 IU/kg of rVIII-SingleChain and for whom a sufficient number of analyzable PK samples were obtained to permit the evaluation of the PK profile. In the Part 1 PK analysis, these subjects also received 1 dose of 50 IU/kg octocog alfa. There were 27 subjects in the PK population (Part 1).
Overall Number of Participants Analyzed 27
Mean (Standard Deviation)
Unit of Measure: hours
Octocog alfa 13.3  (4.36)
rVIII-SingleChain 14.5  (3.77)
9.Secondary Outcome
Title Mean Residence Time (MRT) (Part 1)
Hide Description Mean residence time (MRT) of a single infusion of octocog alfa and rVIII-SingleChain without correction for subject's predose plasma FVIII activity.
Time Frame Before infusion and at up to 10 time points within 72 hours of infusion
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK Population (Part 1)
Hide Arm/Group Description:
The PK population (Part 1) consisted of subjects who had received 1 dose of 50 IU/kg of rVIII-SingleChain and for whom a sufficient number of analyzable PK samples were obtained to permit the evaluation of the PK profile. In the Part 1 PK analysis, these subjects also received 1 dose of 50 IU/kg octocog alfa. There were 27 subjects in the PK population (Part 1).
Overall Number of Participants Analyzed 27
Mean (Standard Deviation)
Unit of Measure: hours
Octocog alfa 17.1  (5.57)
rVIII-SingleChain 20.4  (5.49)
10.Secondary Outcome
Title Clearance (Cl) (Part 1)
Hide Description Clearance (Cl) of a single infusion of octocog alfa and rVIII-SingleChain without correction for subject's predose plasma FVIII activity. FVIII activity values for octocog alfa are dose-adjusted for chromogenic potency.
Time Frame Before infusion and at up to 10 time points within 72 hours of infusion
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK Population (Part 1)
Hide Arm/Group Description:
The PK population (Part 1) consisted of subjects who had received 1 dose of 50 IU/kg of rVIII-SingleChain and for whom a sufficient number of analyzable PK samples were obtained to permit the evaluation of the PK profile. In the Part 1 PK analysis, these subjects also received 1 dose of 50 IU/kg octocog alfa. There were 27 subjects in the PK population (Part 1).
Overall Number of Participants Analyzed 27
Mean (Standard Deviation)
Unit of Measure: mL/h/kg
Octocog alfa 3.68  (1.41)
rVIII-SingleChain 2.64  (0.846)
11.Secondary Outcome
Title Volume of Distribution at Steady-state (Vss) (Part 1)
Hide Description Volume of distribution at steady-state (Vss) of a single infusion of octocog alfa and rVIII-SingleChain without correction for subject's predose plasma FVIII activity. FVIII activity values for octocog alfa are dose-adjusted for chromogenic potency.
Time Frame Before infusion and at up to 10 time points within 72 hours of infusion
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK Population (Part 1)
Hide Arm/Group Description:
The PK population (Part 1) consisted of subjects who had received 1 dose of 50 IU/kg of rVIII-SingleChain and for whom a sufficient number of analyzable PK samples were obtained to permit the evaluation of the PK profile. In the Part 1 PK analysis, these subjects also received 1 dose of 50 IU/kg octocog alfa. There were 27 subjects in the PK population (Part 1).
Overall Number of Participants Analyzed 27
Mean (Standard Deviation)
Unit of Measure: mL/kg
Octocog alfa 57.1  (11.3)
rVIII-SingleChain 50.0  (7.51)
12.Secondary Outcome
Title Incremental Recovery (Part 1)
Hide Description Incremental recovery of a single infusion of octocog alfa and rVIII-SingleChain with correction for subject's predose plasma FVIII activity. FVIII activity values for octocog alfa are dose-adjusted for chromogenic potency.
Time Frame At 30 minutes after infusion
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PK Population (Part 1)
Hide Arm/Group Description:
The PK population (Part 1) consisted of subjects who had received 1 dose of 50 IU/kg of rVIII-SingleChain and for whom a sufficient number of analyzable PK samples were obtained to permit the evaluation of the PK profile. In the Part 1 PK analysis, these subjects also received 1 dose of 50 IU/kg octocog alfa. There were 27 subjects in the PK population (Part 1).
Overall Number of Participants Analyzed 27
Mean (Standard Deviation)
Unit of Measure: [IU/dL]/[IU/kg]
Octocog alfa 2.32  (0.381)
rVIII-SingleChain 2.24  (0.357)
13.Secondary Outcome
Title Annualized Bleeding Rate for Total Bleeds and Traumatic Bleeds
Hide Description The annualized bleeding rate was derived for each subject as follows: 365.25*(number of bleeding episodes requiring treatment) / (observed treatment period of interest).
Time Frame Up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title rVIII-SingleChain On-demand rVIII-SingleChain Prophylaxis
Hide Arm/Group Description:
The rVIII-SingleChain On-demand group consisted of all subjects in the efficacy population who received at least 1 dose rVIII-SingleChain as part of on-demand treatment during Parts 2 or 3 of the study. There were 27 subjects in the rVIII-SingleChain On-demand group.
The rVIII-SingleChain Prophylaxis group consisted of all subjects in the efficacy population who received at least 1 dose rVIII-SingleChain as part of routine prophylaxis treatment during Parts 2 or 3 of the study. There were 146 subjects in the rVIII-SingleChain Prophylaxis group.
Overall Number of Participants Analyzed 27 146
Median (Inter-Quartile Range)
Unit of Measure: Number of bleeds per year
Total Bleeds
19.64
(6.2 to 46.5)
1.14
(0.0 to 4.2)
Traumatic Bleeds
3.12
(0.0 to 8.4)
0.00
(0.0 to 0.9)
14.Secondary Outcome
Title Proportion of Bleeding Episodes Requiring 1, 2, 3 or > 3 Infusions of rVIII-SingleChain to Achieve Hemostasis
Hide Description Percentage of bleeding episodes requiring 1, 2, 3 or > 3 infusions of rVIII-SingleChain to achieve hemostasis. The denominator includes all treated bleeding episodes.
Time Frame During the study (up to 24 months; assessed at Months 1, 2, 3, 4, 5, 6, 9, 12, 15, 18, 21 and 24)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title rVIII-SingleChain On-demand rVIII-SingleChain Prophylaxis rVIII-SingleChain
Hide Arm/Group Description:
The rVIII-SingleChain On-demand group consisted of all subjects in the efficacy population who received at least 1 dose rVIII-SingleChain as part of on-demand treatment during Parts 2 or 3 of the study. There were 27 subjects in the rVIII-SingleChain On-demand group.
The rVIII-SingleChain Prophylaxis group consisted of all subjects in the efficacy population who received at least 1 dose rVIII-SingleChain as part of routine prophylaxis treatment during Parts 2 or 3 of the study. There were 146 subjects in the rVIII-SingleChain Prophylaxis group.
The Efficacy population consisted of all subjects who received at least one dose of rVIII-SingleChain as part of either routine prophylaxis treatment or on-demand treatment during Parts 2 or 3 of the study. There were 173 subjects in the Efficacy population.
Overall Number of Participants Analyzed 27 146 173
Overall Number of Units Analyzed
Type of Units Analyzed: Treated bleeding episodes
 590 258 848
Measure Type: Number
Unit of Measure: Percentage of bleeding episodes
Requiring 1 infusion for hemostasis 82.7 76.7 80.9
Requiring 2 infusions for hemostasis 12.0 14.0 12.6
Requiring 3 infusions for hemostasis 3.22 3.88 3.42
Requiring >3 infusions for hemostasis 2.03 5.43 3.07
15.Other Pre-specified Outcome
Title Incremental Recovery (Part 3)
Hide Description Incremental recovery of an initial and repeat infusion of rVIII-SingleChain with correction for subject's predose plasma FVIII activity.
Time Frame At 30 minutes after infusion
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title rVIII-SingleChain PK Population (Part 3)
Hide Arm/Group Description:
The rVIII-SingleChain PK population (Part 3) consisted of subjects who received rVIII-SingleChain during Part 3 of the study (initial and repeat dose) and for whom a sufficient number of analyzable PK samples were obtained to permit the evaluation of the PK profile. In Part 3, 64 subjects participated in the initial PK, of whom 30 also participated in the repeat PK.
Overall Number of Participants Analyzed 63
Mean (Standard Deviation)
Unit of Measure: [IU/dL]/[IU/kg]
Initial, n = 63 1.85  (0.404)
Repeat, n = 29 1.99  (0.352)
16.Other Pre-specified Outcome
Title Volume of Distribution at Steady-state (Vss) (Part 3)
Hide Description Volume of distribution at steady-state (Vss) of an initial and repeat infusion of rVIII-SingleChain without correction for subject's predose plasma FVIII activity.
Time Frame Before infusion and at up to 12 time points within 96 hours of infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title rVIII-SingleChain PK Population (Part 3)
Hide Arm/Group Description:
The rVIII-SingleChain PK population (Part 3) consisted of subjects who received rVIII-SingleChain during Part 3 of the study (initial and repeat dose) and for whom a sufficient number of analyzable PK samples were obtained to permit the evaluation of the PK profile. In Part 3, 64 subjects participated in the initial PK, of whom 30 also participated in the repeat PK.
Overall Number of Participants Analyzed 64
Mean (Standard Deviation)
Unit of Measure: mL/kg
Initial, n = 64 59.5  (14.2)
Repeat, n = 30 53.1  (8.74)
17.Other Pre-specified Outcome
Title Clearance (Cl) (Part 3)
Hide Description Clearance (Cl) of an initial and repeat infusion of rVIII-SingleChain without correction for subject's predose plasma FVIII activity.
Time Frame Before infusion and at up to 12 time points within 96 hours of infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title rVIII-SingleChain PK Population (Part 3)
Hide Arm/Group Description:
The rVIII-SingleChain PK population (Part 3) consisted of subjects who received rVIII-SingleChain during Part 3 of the study (initial and repeat dose) and for whom a sufficient number of analyzable PK samples were obtained to permit the evaluation of the PK profile. In Part 3, 64 subjects participated in the initial PK, of whom 30 also participated in the repeat PK.
Overall Number of Participants Analyzed 64
Mean (Standard Deviation)
Unit of Measure: mL/h/kg
Initial, n = 64 3.15  (1.21)
Repeat, n = 30 3.05  (1.1)
18.Other Pre-specified Outcome
Title Mean Residence Time (MRT) (Part 3)
Hide Description Mean residence time (MRT) of an initial and repeat infusion of rVIII-SingleChain without correction for subject's predose plasma FVIII activity.
Time Frame Before infusion and at up to 12 time points within 96 hours of infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title rVIII-SingleChain PK Population (Part 3)
Hide Arm/Group Description:
The rVIII-SingleChain PK population (Part 3) consisted of subjects who received rVIII-SingleChain during Part 3 of the study (initial and repeat dose) and for whom a sufficient number of analyzable PK samples were obtained to permit the evaluation of the PK profile. In Part 3, 64 subjects participated in the initial PK, of whom 30 also participated in the repeat PK.
Overall Number of Participants Analyzed 64
Mean (Standard Deviation)
Unit of Measure: hours
Initial, n = 64 20.3  (5.36)
Repeat, n = 30 18.9  (5.39)
19.Other Pre-specified Outcome
Title Half-life (t1/2) (Part 3)
Hide Description Half-life (t1/2) of an initial and repeat infusion of rVIII-SingleChain without correction for subject's predose plasma FVIII activity.
Time Frame Before infusion and at up to 12 time points within 96 hours of infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title rVIII-SingleChain PK Population (Part 3)
Hide Arm/Group Description:
The rVIII-SingleChain PK population (Part 3) consisted of subjects who received rVIII-SingleChain during Part 3 of the study (initial and repeat dose) and for whom a sufficient number of analyzable PK samples were obtained to permit the evaluation of the PK profile. In Part 3, 64 subjects participated in the initial PK, of whom 30 also participated in the repeat PK.
Overall Number of Participants Analyzed 64
Mean (Standard Deviation)
Unit of Measure: hours
Initial, n = 64 14.1  (3.82)
Repeat, n = 30 12.9  (3.7)
20.Other Pre-specified Outcome
Title Tmax (Part 3)
Hide Description Tmax = time of Cmax (with correction for subject's predose plasma FVIII activity) after an initial and repeat infusion of rVIII-SingleChain.
Time Frame Before infusion and at up to 12 time points within 96 hours of infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title rVIII-SingleChain PK Population (Part 3)
Hide Arm/Group Description:
The rVIII-SingleChain PK population (Part 3) consisted of subjects who received rVIII-SingleChain during Part 3 of the study (initial and repeat dose) and for whom a sufficient number of analyzable PK samples were obtained to permit the evaluation of the PK profile. In Part 3, 64 subjects participated in the initial PK, of whom 30 also participated in the repeat PK.
Overall Number of Participants Analyzed 63
Median (Full Range)
Unit of Measure: hours
Initial, n = 63
0.333
(0.117 to 1.22)
Repeat, n = 29
0.317
(0.117 to 0.667)
21.Other Pre-specified Outcome
Title Cmax (Part 3)
Hide Description Cmax of an initial and repeat infusion of rVIII-SingleChain with correction for subject's predose plasma FVIII activity.
Time Frame Before infusion and at up to 12 time points within 96 hours of infusion
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title rVIII-SingleChain PK Population (Part 3)
Hide Arm/Group Description:
The rVIII-SingleChain PK population (Part 3) consisted of subjects who received rVIII-SingleChain during Part 3 of the study (initial and repeat dose) and for whom a sufficient number of analyzable PK samples were obtained to permit the evaluation of the PK profile. In Part 3, 64 subjects participated in the initial PK, of whom 30 also participated in the repeat PK.
Overall Number of Participants Analyzed 63
Mean (Standard Deviation)
Unit of Measure: IU/dL
Initial, n = 63 99.9  (19.9)
Repeat, n = 29 108  (18.5)
22.Other Pre-specified Outcome
Title AUC0-∞ (Part 3)
Hide Description AUC0-∞ (AUC from 0 extrapolated to infinity) of an initial and repeat infusion of rVIII-SingleChain without correction for subject's predose plasma FVIII activity.
Time Frame Before infusion and at up to 12 time points within 96 hours of infusion
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title rVIII-SingleChain PK Population (Part 3)
Hide Arm/Group Description:
The rVIII-SingleChain PK population (Part 3) consisted of subjects who received rVIII-SingleChain during Part 3 of the study (initial and repeat dose) and for whom a sufficient number of analyzable PK samples were obtained to permit the evaluation of the PK profile. In Part 3, 64 subjects participated in the initial PK, of whom 30 also participated in the repeat PK.
Overall Number of Participants Analyzed 64
Mean (Standard Deviation)
Unit of Measure: IU*h/dL
Initial, n = 64 1830  (640)
Repeat, n = 30 1880  (649)
Time Frame For the duration of the study, approximately 2 years, 10 months.
Adverse Event Reporting Description The Safety Population comprised all subjects treated with rVIII-SingleChain. A total of 14592 rVIII-SingleChain infusions were administered to 174 subjects during the study.
 
Arm/Group Title Safety Population
Hide Arm/Group Description The Safety Population comprised all subjects treated with rVIII-SingleChain.
All-Cause Mortality
Safety Population
Affected / at Risk (%)
Total   --/--    
Hide Serious Adverse Events
Safety Population
Affected / at Risk (%) # Events
Total   8/174 (4.60%)    
Blood and lymphatic system disorders   
Anaemia † 1  1/174 (0.57%)  1
Thrombocytopenia † 1  1/174 (0.57%)  1
Gastrointestinal disorders   
Varices oesophageal † 1  1/174 (0.57%)  1
Immune system disorders   
Hypersensitivity † 1  1/174 (0.57%)  1
Infections and infestations   
Postoperative wound infection † 1  1/174 (0.57%)  1
Viral infection † 1  1/174 (0.57%)  1
Injury, poisoning and procedural complications   
Ankle fracture † 1  1/174 (0.57%)  1
Investigations   
Blood uric acid increased † 1  1/174 (0.57%)  1
Psychiatric disorders   
Suicidal ideation † 1  1/174 (0.57%)  1
Respiratory, thoracic and mediastinal disorders   
Tonsillar haemorrhage † 1  1/174 (0.57%)  1
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (14.1)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Safety Population
Affected / at Risk (%) # Events
Total   45/174 (25.86%)    
Infections and infestations   
Nasopharyngitis † 1  18/174 (10.34%)  22
Musculoskeletal and connective tissue disorders   
Arthralgia † 1  20/174 (11.49%)  22
Nervous system disorders   
Headache † 1  13/174 (7.47%)  14
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (14.1)
[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
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: CSL Behring
ClinicalTrials.gov Identifier: NCT01486927    
Other Study ID Numbers: CSL627_1001
2011-002393-23 ( EudraCT Number )
First Submitted: November 19, 2011
First Posted: December 7, 2011
Results First Submitted: June 24, 2016
Results First Posted: August 9, 2016
Last Update Posted: August 9, 2016