Clinical Trial Results:
A Phase 2/3, Multi-Center, Open Label Study of Efficacy, Safety, and Pharmacokinetics of PEGylated Recombinant Factor VIII (BAX 855) Administered for Prophylaxis and Treatment of Bleeding in Previously Treated Patients with Severe Hemophilia A
Summary
|
|
EudraCT number |
2012-003599-38 |
Trial protocol |
DE GB AT LT CZ SE ES BE NL BG PL HU RO |
Global end of trial date |
17 Jul 2014
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
18 Feb 2016
|
First version publication date |
05 Aug 2015
|
Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
Trial identification
|
|||
Sponsor protocol code |
261201
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
|
|||
Sponsor organisation name |
Baxalta Innovations GmbH
|
||
Sponsor organisation address |
Industriestrasse 67, Vienna, Austria, 1221
|
||
Public contact |
Clinical Trial Registries and Results Disclosure, Baxalta Innovations GmbH, ClinicalTrialsDisclosure@baxalta.com
|
||
Scientific contact |
Clinical Trial Registries and Results Disclosure, Baxalta Innovations GmbH, ClinicalTrialsDisclosure@baxalta.com
|
||
Sponsor organisation name |
Baxalta US Inc
|
||
Sponsor organisation address |
One Baxter Way, Westlake Village CA, United States, 91362-3811
|
||
Public contact |
Clinical Trial Registries and Results Disclosure, Baxalta US Inc, ClinicalTrialsDisclosure@baxalta.com
|
||
Scientific contact |
Clinical Trial Registries and Results Disclosure, Baxalta US Inc, ClinicalTrialsDisclosure@baxalta.com
|
||
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
|
||
EMA paediatric investigation plan number(s) |
EMEA-001296-PIP01-12 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
17 Jul 2014
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
17 Jul 2014
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
17 Jul 2014
|
||
Was the trial ended prematurely? |
No
|
||
General information about the trial
|
|||
Main objective of the trial |
Compare the annualized rates of bleeding episodes (ABR) between subjects who received a prophylactic dosing regimen of BAX 855 with those who received an on-demand treatment regimen
|
||
Protection of trial subjects |
This study was conducted in accordance with the standards of Good Clinical Practice (GCP) in effect at the time of the study.
Justification for enrollment of adolescent subjects was based on requirements outlined in
the ICH M3 Guideline, Section 12 as well as the ICH E11 Guideline on clinical investigation of medicinal products in the pediatric population.Baxalta follows a stepwise approach and starts the clinical investigation of efficacy and safety in patients ≥12 years before starting studies in patients < 12 years.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
31 Jan 2013
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
United States: 32
|
||
Country: Number of subjects enrolled |
Australia: 6
|
||
Country: Number of subjects enrolled |
Japan: 11
|
||
Country: Number of subjects enrolled |
Malaysia: 9
|
||
Country: Number of subjects enrolled |
Korea, Republic of: 10
|
||
Country: Number of subjects enrolled |
Taiwan: 1
|
||
Country: Number of subjects enrolled |
Austria: 7
|
||
Country: Number of subjects enrolled |
Bulgaria: 1
|
||
Country: Number of subjects enrolled |
Czech Republic: 7
|
||
Country: Number of subjects enrolled |
Germany: 5
|
||
Country: Number of subjects enrolled |
Israel: 4
|
||
Country: Number of subjects enrolled |
Lithuania: 6
|
||
Country: Number of subjects enrolled |
Netherlands: 1
|
||
Country: Number of subjects enrolled |
Poland: 6
|
||
Country: Number of subjects enrolled |
Romania: 2
|
||
Country: Number of subjects enrolled |
Spain: 8
|
||
Country: Number of subjects enrolled |
Sweden: 3
|
||
Country: Number of subjects enrolled |
Switzerland: 2
|
||
Country: Number of subjects enrolled |
Ukraine: 9
|
||
Country: Number of subjects enrolled |
United Kingdom: 8
|
||
Worldwide total number of subjects |
138
|
||
EEA total number of subjects |
54
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
25
|
||
Adults (18-64 years) |
113
|
||
From 65 to 84 years |
0
|
||
85 years and over |
0
|
|
|||||||||||||||||||||||||
Recruitment
|
|||||||||||||||||||||||||
Recruitment details |
Subjects were enrolled (signed informed consent) from 72 sites. | ||||||||||||||||||||||||
Pre-assignment
|
|||||||||||||||||||||||||
Screening details |
A total of 159 subjects provided informed consent and were screened for study participation, of which there were 21 screen failures. 138 subjects were assigned to the prophylactic arm or the on-demand treatment regimen. | ||||||||||||||||||||||||
Pre-assignment period milestones
|
|||||||||||||||||||||||||
Number of subjects started |
159 [1] | ||||||||||||||||||||||||
Number of subjects completed |
138 | ||||||||||||||||||||||||
Pre-assignment subject non-completion reasons
|
|||||||||||||||||||||||||
Reason: Number of subjects |
Screen failures: 21 | ||||||||||||||||||||||||
Notes [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: A total of 159 subjects provided informed consent and were screened for study participation, of which there were 21 screen failures. 138 subjects were assigned to the prophylactic arm or the on-demand treatment regimen. |
|||||||||||||||||||||||||
Period 1
|
|||||||||||||||||||||||||
Period 1 title |
Overall Trial (overall period)
|
||||||||||||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||||||||||||
Allocation method |
Non-randomised - controlled
|
||||||||||||||||||||||||
Blinding used |
Not blinded | ||||||||||||||||||||||||
Arms
|
|||||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
||||||||||||||||||||||||
Arm title
|
Arm A: Prophylactic treatment | ||||||||||||||||||||||||
Arm description |
Prophylactic treatment with BAX 855 at a dose of 45 ± 5 IU/kg twice weekly | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
BAX 855
|
||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||
Pharmaceutical forms |
Infusion
|
||||||||||||||||||||||||
Routes of administration |
Intravenous bolus use
|
||||||||||||||||||||||||
Dosage and administration details |
45 ± 5 IU/kg twice weekly
|
||||||||||||||||||||||||
Arm title
|
Arm B: On-demand treatment | ||||||||||||||||||||||||
Arm description |
On-demand therapy with BAX 855 at a dose of 10 to 60 IU/kg dose | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
BAX 855
|
||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||
Pharmaceutical forms |
Infusion
|
||||||||||||||||||||||||
Routes of administration |
Intravenous bolus use
|
||||||||||||||||||||||||
Dosage and administration details |
10 to 60 IU/kg dose
|
||||||||||||||||||||||||
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Arm A: Prophylactic treatment
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Prophylactic treatment with BAX 855 at a dose of 45 ± 5 IU/kg twice weekly | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Arm B: On-demand treatment
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
On-demand therapy with BAX 855 at a dose of 10 to 60 IU/kg dose | ||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis sets
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
Full Analysis Set
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Comprised all subjects who were assigned to the prophylactic arm or the on-demand treatment regimen
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
Pharmacokinetic Full Analysis Set
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Sub-group analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Comprised all subjects in Arm A who consented to PK evaluation, who were treated with at least 1 ADVATE and 1 BAX 855 PK dose, and who were evaluable for PK for the ADVATE and initial BAX 855 PK infusions (PK-1
and PK-2). Subjects were PK evaluable if they had at least 3 post-infusion FVIII
measurements above the limit of quantification (LoQ) before the first FVIII measurement
below the LoQ.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
Safety Analysis Set
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Safety analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Comprised all subjects treated with at least 1 BAX 855 dose.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
Arm A: Prophylactic treatment
|
||
Reporting group description |
Prophylactic treatment with BAX 855 at a dose of 45 ± 5 IU/kg twice weekly | ||
Reporting group title |
Arm B: On-demand treatment
|
||
Reporting group description |
On-demand therapy with BAX 855 at a dose of 10 to 60 IU/kg dose | ||
Subject analysis set title |
Full Analysis Set
|
||
Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Comprised all subjects who were assigned to the prophylactic arm or the on-demand treatment regimen
|
||
Subject analysis set title |
Pharmacokinetic Full Analysis Set
|
||
Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Comprised all subjects in Arm A who consented to PK evaluation, who were treated with at least 1 ADVATE and 1 BAX 855 PK dose, and who were evaluable for PK for the ADVATE and initial BAX 855 PK infusions (PK-1
and PK-2). Subjects were PK evaluable if they had at least 3 post-infusion FVIII
measurements above the limit of quantification (LoQ) before the first FVIII measurement
below the LoQ.
|
||
Subject analysis set title |
Safety Analysis Set
|
||
Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Comprised all subjects treated with at least 1 BAX 855 dose.
|
|
|||||||||||||
End point title |
Annualized Bleeding Episode Rates (ABRs) | ||||||||||||
End point description |
Comparisons between prophylactic and on-demand treatment were based on ABR estimates from a negative binomial regression model, taking into account the treatment regimen, target joints and age at screening, and duration of the observation period for efficacy.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
At least 50 exposure days or 6 months (±2 weeks), whichever occurs last, for the prophylaxis arm and 6 months (± 2 weeks) for the on-demand arm.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Ratio Annualized Bleeding Rate Prophyl./On-demand | ||||||||||||
Statistical analysis description |
Ratio Annualized Bleeding Rate (ABR) Prophylaxis/On-demand:
Prophylaxis treatment will be considered to be successful if the upper limit of the 95% CI for the ratio between treatment regimen does not exceed 0.5 (corresponding to a 50% reduction of the mean ABR compared to the on-demand treatment).
H01: μ1 ≥0.5*μ2 Ha1: μ1<0.5*μ2 where μ1 and μ2 are the mean ABRs in on prophylaxis and on-demand, respectively
|
||||||||||||
Comparison groups |
Arm A: Prophylactic treatment v Arm B: On-demand treatment
|
||||||||||||
Number of subjects included in analysis |
137
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 | ||||||||||||
Method |
Regression, Negative binomial | ||||||||||||
Parameter type |
Ratio of means | ||||||||||||
Point estimate |
0.1
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.06 | ||||||||||||
upper limit |
0.19 |
|
|||||||||
End point title |
Rate of success for BAX 855 treatment of bleeding episodes | ||||||||
End point description |
Success in the control of bleeding was defined as a rating of excellent or good using the Efficacy Rating Scale for Treatment of Bleeding Episodes measured 24 hours after initiation of treatment for the bleeding episode.
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 is required for the control of bleeding. Administration of further infusions to maintain hemostasis would 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 a single infusion. Required more than 1 infusion for complete resolution.
NONE: No improvement or condition worsens.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
All bleeding episodes treated with BAX 855 in subjects on on-demand and prophylaxis treatment regimens. At least 50 exposure days or 6 months (±2 weeks), whichever occurs last, for the prophylaxis arm and 6 months (± 2 weeks) for the on-demand arm.
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Total weight-adjusted consumption of BAX 855 | ||||||||||||||||
End point description |
|||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
At least 50 exposure days or 6 months (±2 weeks), whichever occurs last, for the prophylaxis arm and 6 months (± 2 weeks) for the on-demand arm.
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of Subjects with Positive Inhibitory Antibodies to FVIII, Binding Antibodies to FVIII, BAX 855, PEG and Anti-CHO Antibodies at Study Completion/Termination | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Note for Inhibitory Antibodies to FVIII: Subjects = 112 for Arm A; 14 for Arm B; 126 for Safety Analysis Set.
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
From first exposure to BAX 855 until the end of the study [at least 50 exposure days or 6 months (±2 weeks), whichever occurs last, for the prophylaxis arm and 6 months (± 2 weeks) for the on-demand arm].
|
||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Safety - Occurrence of adverse events (AEs) following BAX 855 administration | ||||||||||||||||||||||||
End point description |
Abbreviations: serious adverse event - SAE; non-serious adverse event - nSAE
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
From first exposure to BAX 855 until the end of the study [at least 50 exposure days or 6 months (±2 weeks), whichever occurs last, for the prophylaxis arm and 6 months (± 2 weeks) for the on-demand arm].
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||
End point title |
Terminal half-life (One-stage Clotting) | ||||||||||||||
End point description |
Terminal half-life of BAX 855 following initial and repeat administration after at least 50 exposure days, and as compared to ADVATE. Terminal half-life calculated as log_e2/λ where λ is the terminal elimination rate constant calculate by WinNonlin NCA (Model 201, curve stripping as described in the User’s Guide, page 263). Subjects: 26 subjects for PK1 and PK2; 22 subjects for PK3
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
Pharmacokinetic (PK) evaluation: Within 30 minutes prior to start of infusion; and post-infusion at 10, 30 minutes, and 1, 3, 6, 9, 24, 32, 48, 56, 72 (PK2 and PK3 only), and 96 hours (PK2 and PK3 only).
|
||||||||||||||
|
|||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||
End point title |
Mean Residence Time (One-stage Clotting) | ||||||||||||||
End point description |
Mean Residence Time (One-stage Clotting) of BAX 855 following initial and repeat administration after at least 50 exposure days, and as compared to ADVATE.
The mean residence time (MRT) was calculated as total area under the moment curve divided by the total area under the curve starting from the begin of infusion (or the end of infusion if start time is not available).
Subjects: 26 subjects for PK1 and PK2; 22 subjects for PK3
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
Pharmacokinetic (PK) evaluation: Within 30 minutes prior to start of infusion; and post-infusion at 10, 30 minutes, and 1, 3, 6, 9, 24, 32, 48, 56, 72 (PK2 and PK3 only), and 96 hours (PK2 and PK3 only).
|
||||||||||||||
|
|||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||
End point title |
Total body clearance (One-stage Clotting) | ||||||||||||||
End point description |
Total body clearance (One-stage Clotting) of BAX 855 following initial and repeat administration after at least 50 EDs, and as compared to ADVATE.
Clearance in dL/(kg*hours) was calculated as the dose in IU/kg divided by the total area under the curve starting from the begin of infusion (or the end of infusion if start time is not available).
Subjects: 26 subjects for PK1 and PK2; 22 subjects for PK3.
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
Pharmacokinetic (PK) evaluation: Within 30 minutes prior to start of infusion; and post-infusion at 10, 30 minutes, and 1, 3, 6, 9, 24, 32, 48, 56, 72 (PK2 and PK3 only), and 96 hours (PK2 and PK3 only).
|
||||||||||||||
|
|||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||
End point title |
Incremental recovery (One-stage Clotting) | ||||||||||||||
End point description |
Incremental recovery (One-stage Clotting) of BAX 855 following initial and repeat administration after at least 50 EDs, and as compared to ADVATE.
Subjects: 26 subjects for PK1 and PK2; 22 subjects for PK3
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
Pharmacokinetic (PK) evaluation: Within 30 minutes prior to start of infusion; and post-infusion at 10, 30 minutes, and 1, 3, 6, 9, 24, 32, 48, 56, 72 (PK2 and PK3 only), and 96 hours (PK2 and PK3 only).
|
||||||||||||||
|
|||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||
End point title |
Patient Reporting Outcome Short Form (SF)-36 | ||||||||||||||||||||||||||||||||||||||||||
End point description |
Change from Baseline to Completion of Study for SF-36 Questionnaire is provided.
Scores for individual SF-36 categories range from 0 to 100 with higher scores representing better health.
Given that higher scores indicate better health-related quality of life (HRQoL) and that the change scores were calculated as the value at study completion minus the value at baseline, a negative change score indicates a worsening of HRQoL.
Subjects for Treatment Arm A (prophylactic treatment): 97 subjects for physical functioning, role-physical, bodily pain, social functioning, role emotional; 96 for general health, vitality, mental health, physical component score, mental component score.
|
||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
From screening to end of study visit [at least 50 exposure days or 6 months (±2 weeks), whichever occurs last, for the prophylaxis arm and 6 months (± 2 weeks) for the on-demand arm].
|
||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||
End point title |
Patient Reporting Outcome Haemo-SYM Questionnaire | |||||||||||||||||||||
End point description |
Change from Baseline to Completion of Study for Haemo-SYM Questionnaire. The 17-item HAEMO-SYM has two subscales: pain and bleeds. Given that higher scores indicate more severe symptoms on the Haemo-SYM and that the change scores were calculated as the value at study completion minus the value at
baseline, a negative change score indicates an improvement (reduction in symptoms). Conversely, a positive change score indicates worsening symptoms.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
From screening to end of study visit [at least 50 exposure days or 6 months (±2 weeks), whichever occurs last, for the prophylaxis arm and 6 months (± 2 weeks) for the on-demand arm].
|
|||||||||||||||||||||
|
||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Average number of BAX855 infusions needed for the treatment of bleeding episodes | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From first exposure to BAX 855 until the end of the study [at least 50 exposure days or 6 months (±2 weeks), whichever occurs last, for the prophylaxis arm and 6 months (± 2 weeks) for the on-demand arm].
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||
End point title |
Time intervals between bleeding episodes | |||||||||||||||||||||||||||||||||
End point description |
Interval between Bleeds in months was calculated as:
Observation period for efficacy (in days)/(number of bleeds)*(12/365.2425)
|
|||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||
End point timeframe |
From first exposure to BAX 855 until the end of the study [at least 50 exposure days or 6 months (±2 weeks), whichever occurs last, for the prophylaxis arm and 6 months (± 2 weeks) for the on-demand arm].
|
|||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||
End point title |
Area under the concentration versus time curve from 0 to infinity (One-stage Clotting) | ||||||||||||||
End point description |
Area under the concentration versus time curve from 0 to infinity of BAX 855 following initial and repeat administration after at least 50 EDs, and as compared to ADVATE. Calculated by WinNonlin NCA (Model 201, calculation method: Linear Trapezoidal Linear/Log Interpolation).
Subjects: 26 subjects for PK1 and PK2; 22 subjects for PK3
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
Pharmacokinetic (PK) evaluation: Within 30 minutes prior to start of infusion; and post-infusion at 10, 30 minutes, and 1, 3, 6, 9, 24, 32, 48, 56, 72 (PK2 and PK3 only), and 96 hours (PK2 and PK3 only).
|
||||||||||||||
|
|||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||
End point title |
Apparent Volume of Distribution at Steady State (One-stage Clotting) | ||||||||||||||
End point description |
Apparent Volume of Distribution at Steady State of BAX 855 following initial and repeat administration after at least 50 EDs, and as compared to ADVATE. Calculated as Clearance * Mean Residence Time.
Subjects: 26 subjects for PK1 and PK2; 22 subjects for PK3
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
Pharmacokinetic (PK) evaluation: Within 30 minutes prior to start of infusion; and post-infusion at 10, 30 minutes, and 1, 3, 6, 9, 24, 32, 48, 56, 72 (PK2 and PK3 only), and 96 hours (PK2 and PK3 only).
|
||||||||||||||
|
|||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||
End point title |
Maximum plasma concentration (One-stage Clotting) | ||||||||||||||
End point description |
Maximum plasma concentration of BAX 855 following initial and repeat administration after at least 50 EDs, and as compared to ADVATE. Determined as the maximum concentration achieved post-infusion.
Subjects: 26 subjects for PK1 and PK2; 22 subjects for PK3
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
Pharmacokinetic (PK) evaluation: Within 30 minutes prior to start of infusion; and post-infusion at 10, 30 minutes, and 1, 3, 6, 9, 24, 32, 48, 56, 72 (PK2 and PK3 only), and 96 hours (PK2 and PK3 only).
|
||||||||||||||
|
|||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||
End point title |
Time to maximum concentration in plasma (One-stage Clotting) | ||||||||||||||
End point description |
Time to maximum concentration in plasma of BAX 855 following initial and repeat administration after at least 50 EDs, and as compared to ADVATE. Defined as the time to reach maximum plasma concentration.
Subjects: 26 subjects for PK1 and PK2; 22 subjects for PK3
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
Pharmacokinetic (PK) evaluation: Within 30 minutes prior to start of infusion; and post-infusion at 10, 30 minutes, and 1, 3, 6, 9, 24, 32, 48, 56, 72 (PK2 and PK3 only), and 96 hours (PK2 and PK3 only).
|
||||||||||||||
|
|||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
From first exposure to BAX 855 until the end of the study [at least 50 exposure days or 6 months (±2 weeks), whichever occurs last, for the prophylaxis arm and 6 months (± 2 weeks) for the on-demand arm].
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
The population consisted of subjects who received at least one dose of BAX 855 during the study.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Safety Analysis Set
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Comprised all subjects treated with at least 1 BAX 855 dose. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |