Clinical Trial Results:
Clinical Study to Investigate the Efficacy, Safety, and Immunogenicity of human-cl rhFVIII in Previously Treated Patients With Severe Haemophilia A
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Summary
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EudraCT number |
2009-011055-43 |
Trial protocol |
DE AT GB |
Global end of trial date |
31 Jan 2012
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Results information
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Results version number |
v1(current) |
This version publication date |
09 Oct 2016
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First version publication date |
09 Oct 2016
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
GENA-08
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01125813 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Octapharma AG
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Sponsor organisation address |
Seidenstraße 2, Lachen, Switzerland, CH-8853
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Public contact |
Johann Bichler, Octapharma AG, +41 (0)554512177, johann.bichler@octapharma.ch
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Scientific contact |
Johann Bichler, Octapharma AG, +41 (0)554512177, johann.bichler@octapharma.ch
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-001024-PIP01-10 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
19 Jul 2012
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Jan 2012
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To determine in previously treated subjects suffering from severe haemophilia A the efficacy of human-cl rhFVIII during prophylactic treatment, in the treatment of bleeding episodes and in surgical prophylaxis.
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Protection of trial subjects |
This trial was conducted in accordance with the ethical principles laid down in the Declaration of Helsinki. It was submitted to an IEC and it was conducted in compliance with the protocol, GCP regulations and applicable regulatory requirements. Inclusion and exclusion criteria were carefully defined in order to protect subjects from contraindications, interactions with other medication and safety factors associated with the IMP.
Thoughout the study safety was assessed such as occurrence of AEs, measuring vital signs and routine safety laboratory parameters at pre-defined time points. Also inhibitors against FVIII and anti-rhFVIII antibodies were determined at pre-determined time points.
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Background therapy |
NA | ||
Evidence for comparator |
NA | ||
Actual start date of recruitment |
22 Jun 2010
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 15
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Country: Number of subjects enrolled |
Austria: 1
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Country: Number of subjects enrolled |
Bulgaria: 8
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Country: Number of subjects enrolled |
Germany: 8
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Worldwide total number of subjects |
32
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EEA total number of subjects |
32
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
31
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From 65 to 84 years |
1
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||
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Pre-assignment
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Screening details |
All screened 36. All enrolled 32. Inclusion criteria: must have severe haemophilia A (FVIII:C ≤1%; historical value as documented in patient records), male patients 12 years of age or older, previously treated with FVIII concentrate, at least 150 EDs, immunocompetent (CD4+ count >200/μL), negative for anti-human HIV, freely given written ICF. | ||||||||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||
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Arms
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Arm title
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Human-cl rhFVIII | ||||||||||||
Arm description |
IMP was administerd to all patients prophylactically and for in-vivo recovery assessment and if required for treatment of bleeding episodes or surgical prophylaxis. | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Human-cl rhFVIII
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Investigational medicinal product code |
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Other name |
Nuwiq
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Pharmaceutical forms |
Concentrate and solvent for solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
A dose of 50 IU/kg was administered at Visit 1 and at 3 and 6 month for the purpose of assessing IVR. Prophylactic treatment: patients received 30-40 IU FVIII/kg every other day until 6 months and at least 50 EDs had been reached.
On-demand treatment and surgical prophylaxis: dosage recommendations were given in the protocol.
The IMP was to be administered at a maximum speed of 4 mL/minute.
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
ITT / Subjects on prophylactic treatment (PROPH)
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Subject analysis set type |
Intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All patients in the ITT population who received at least one prophylactic infusion.
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Subject analysis set title |
BLEED population
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Subject analysis set type |
Sub-group analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All documented bleeding episodes (BEs) of patients in the ITT population for which any amount of treatment with Human-cl rhFVIII was documented. A total of 30 BEs that were treated with Human-cl rhFVIII were recorded in 15 patients .
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Subject analysis set title |
SURG population
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Subject analysis set type |
Sub-group analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All documented surgical interventions of patients in the ITT population for which any amount of Human-cl rhFVIII prior to, during or after the surgery was documented and no other FVIII concentrate was documented within 24 hours prior to surgery.
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End points reporting groups
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Reporting group title |
Human-cl rhFVIII
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Reporting group description |
IMP was administerd to all patients prophylactically and for in-vivo recovery assessment and if required for treatment of bleeding episodes or surgical prophylaxis. | ||
Subject analysis set title |
ITT / Subjects on prophylactic treatment (PROPH)
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
All patients in the ITT population who received at least one prophylactic infusion.
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Subject analysis set title |
BLEED population
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
All documented bleeding episodes (BEs) of patients in the ITT population for which any amount of treatment with Human-cl rhFVIII was documented. A total of 30 BEs that were treated with Human-cl rhFVIII were recorded in 15 patients .
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Subject analysis set title |
SURG population
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
All documented surgical interventions of patients in the ITT population for which any amount of Human-cl rhFVIII prior to, during or after the surgery was documented and no other FVIII concentrate was documented within 24 hours prior to surgery.
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End point title |
Overall efficacy assessment of Prophylactic Treatment [1] | ||||||||||||||
End point description |
For prophylactic treatment, primary efficacy variables were the overall efficacy assessment after a total of at least 50 EDs at the end of the study and consumption of IMP (FVIII IU/kg per month, per year) per patient and in total. Prophylactic efficacy is assessed by the monthly bleeding rate (excellent: <0.75, good: 0.75-1.0, moderate: >1.0-1.5; poor: >1.5)
Includes all bleeding episodes between start of prophylactic treatment and last prophylactic treatment + 2 days or study completion, whichever comes first. Bleeding episodes between start of treatment for surgery and re-start of prophylactic treatment after surgery are excluded.
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End point type |
Primary
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End point timeframe |
6 month
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: descriptive analysis - no statistical analysis for this endpoint available |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Amount of Human-cl rhFVIII (IU/kg) for prophylactic treatment per month [2] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Study drug consumption data per month
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: descriptive analysis - no statistical analysis for this endpoint available |
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End point title |
Personal efficacy assessment of treatment of bleeding episode [3] | ||||||||||||||
End point description |
At the end of a BE, the following efficacy assessment was made:
• Excellent: Abrupt pain relief and/or unequivocal improvement in objective signs of bleeding within approximately 8 hours after a single infusion
• Good: Definite pain relief and/or improvement in signs of bleeding within approximately 8–12 hours after an infusion requiring up to 2 infusions for complete resolution
• Moderate: Probable or slight beneficial effect within approximately 12 hours after the first infusion requiring more than two infusions for complete resolution
• None: No improvement within 12 hours, or worsening of symptoms, requiring more than 2 infusions for complete resolution
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End point type |
Primary
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End point timeframe |
Any bleeding epsiode treated with Human-cl rhFVIII during the study
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: descriptive analysis - no statistical analysis for this endpoint available |
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| Notes [4] - Number of bleeding episodes: 28 |
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End point title |
Efficacy evaluation of the use of Human-cl rhFVIII in surgical procedures [5] | ||||||||||||||
End point description |
four point scale
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End point type |
Primary
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End point timeframe |
Overall efficacy assessment after the end of the surgical prophylactic treatment phase by the surgeon and haematologist.
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| Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: descriptive analysis - no statistical analysis for this endpoint available |
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| No statistical analyses for this end point | |||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
The condition of the subject was monitored throughout the study. 24 hours SAE reporting requirement.
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Adverse event reporting additional description |
All SAEs, suspected to be related to study treatment or not, were reported by telephone, fax or e-mail immediately to the responsible CPM, CRA or to local CRO.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
13.1
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Reporting groups
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Reporting group title |
Human-cl rhFVIII
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Reporting group description |
all patients who received at least one dose of Human-cl rhFVIII | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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10 May 2011 |
• As it became clear that the study would take longer than originally anticipated, the planned clinical end was updated from Q1 2011 to Q4 2011.
• In addition to vials containing 500 IU of Human-cl rhFVIII concentrate, also vials containing 1000 IU and 2000 IU were expected to become available during the study. These were included in the description of the IMP.
• In this study, it was allowed to enter certain source data (vital signs, body weight and dates/times of blood drawings) directly into the CRF without prior written or electronic record of source data, turning the CRF into source. This was clarified in the text.
• The final change concerned the documentation of BEs that occurred simultaneously at several sites. It was clarified that if a patient experienced simultaneously BEs at several sites, they each had to be documented as separate BEs. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
