Clinical Trial Results:
PROSPECTIVE CLINICAL STUDY IN CHILDREN WITH SEVERE HAEMOPHILIA A
TO INVESTIGATE CLINICAL EFFICACY, IMMUNOGENICITY, PHARMACOKINETICS,
AND SAFETY OF HUMAN-CL RHFVIII
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Summary
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EudraCT number |
2010-018644-14 |
Trial protocol |
DE AT CZ GB |
Global end of trial date |
06 Nov 2012
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Results information
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Results version number |
v1(current) |
This version publication date |
22 Jul 2016
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First version publication date |
22 Jul 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-03
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Additional study identifiers
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ISRCTN number |
ISRCTN71212110 | ||
US NCT number |
- | ||
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 |
Clinical Research and Development, Octapharma Pharmazeutika Produktionsgesellschaft mbH, +43 1610320,
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Scientific contact |
Clinical Research and Development, Octapharma Pharmazeutika Produktionsgesellschaft mbH, +43 1610320,
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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 |
15 Feb 2013
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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 |
06 Nov 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 |
The primary objective of this clinical study was to assess clinical efficacy of Human-cl rhFVIII in terms of prevention (prophylactic treatment) and treatment of (breakthrough) BEs in previously treated children suffering from severe haemophilia A (FVIII:C <1%)
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Protection of trial subjects |
This trial was conducted in accordance to the principles of GCP, ensuring that the rights, safety and well-being of patients are protected and in consistency with the Declaration of Helsinki.
Inclusion and exclusion criteria were carefully defined in order to protect subjects from contraindications, interactions with other medication and safety factors associated with the investigational medicinal product.
Throughout the study safety was assessed, such as occurrence of AEs, lab values, vital signs and physical examinations.
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Background therapy |
NA | ||
Evidence for comparator |
NA | ||
Actual start date of recruitment |
27 Dec 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 |
Poland: 24
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Country: Number of subjects enrolled |
United Kingdom: 10
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Country: Number of subjects enrolled |
Czech Republic: 2
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Country: Number of subjects enrolled |
France: 2
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Country: Number of subjects enrolled |
Russian Federation: 9
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Country: Number of subjects enrolled |
Turkey: 9
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Country: Number of subjects enrolled |
Romania: 3
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Worldwide total number of subjects |
59
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EEA total number of subjects |
41
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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) |
58
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Adolescents (12-17 years) |
1
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Recruitment period December 2010 - April 2012. PK patients in total 27 (13 patients: 2-5 years, 14 patients: 6-12 years). Non PK-patients in total 32 (16 patients 2-5 years, 16 patients 6-12 years) | ||||||||||||
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Pre-assignment
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Screening details |
All screened 61. All enrolled 59. Inclusion criteria: Severe haemophilia A (FVIII:C <1%);Age ≥2 to 12 years;Previously treated with FVIII concentrate (at least 50 EDs);Immunocompetence (CD4+ count >200/μL);HIV-negative or respective viral load <200 particles/μL or <400,000 copies/mL; patients had to undergo a FVIII wash-out phase of at least 72 hrs | ||||||||||||
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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 | ||||||||||||
Blinding implementation details |
NA
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Arms
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Arm title
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Human-cl rhFVIII | ||||||||||||
Arm description |
Prophylactic and on-demand treatment with Human-cl rhFVIII | ||||||||||||
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 |
Powder and solvent for solution for injection in pre-filled syringe
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Routes of administration |
Intravenous use
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Dosage and administration details |
PK/recovery: 50 IU FVIII/kg body weight (BW) of the previously used FVIII concentrate followed by Human-cl rhFVIII after a wash-out period.
Prophylactic treatment: All patients were treated prophylactically: every other day or 3 times weekly. The recommended dosage regimen was 30–40 IU FVIII/kg BW. Two dose escalations of each +5 IU FVIII/kg BW were allowed in case of an inadequate response (≥2 spontaneous BEs within one month).
Treatment of breakthrough bleeding´s: dosage recommendations depending on the location and severity of the bleed are given in the protocol.
Patients were treated for at least 50 EDs and at least 6 months.
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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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End points reporting groups
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Reporting group title |
Human-cl rhFVIII
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Reporting group description |
Prophylactic and on-demand treatment with Human-cl rhFVIII | ||
Subject analysis set title |
Intention-to-treat
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
All subjects who received at least one dose of Human-cl rhFVIII and for whom any data was collected post treatment with Human-cl rhFVIII
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Subject analysis set title |
Population of BEs (BLEED):
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
All documented BEs of patients in the PROPH population for which treatment with Human-cl rhFVIII was documented. Any type of BE includes: spontaneous, traumatic, post-operative or other bleeding events.
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End point title |
Efficacy of Prophylactic Treatment [1] | ||||||||||||||
End point description |
Overall efficacy assessment
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End point type |
Primary
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End point timeframe |
after 50 EDs and at the end of the study
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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: no statistical analysis for this endpoint available |
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End point title |
Frequency of BEs during prophylaxis [2] | ||||||||
End point description |
Monthly Rate of BEs during Prophylactic Treatment, comprises spontaneous and traumatic BEs
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End point type |
Primary
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End point timeframe |
End of study
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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: no statistical analysis for this endpoint available |
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End point title |
Personal efficacy assessment of treatment of bleeding episodes (four-point rating scale) [3] | ||||||||||||||
End point description |
Overall efficacy assessment
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End point type |
Primary
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End point timeframe |
All bleeding episodes treated with Human-cl rhFVIII between start and end of prophylactic treatment + 2 days or study completion, whichever comes first.
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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: no statistical analysis for this endpoint available |
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Adverse events information
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Timeframe for reporting adverse events |
24 hours SAE reporting requirement.
Waiver from 24 hours SAE reporting: hospitalization for the treatment of a (disease-related) BE.
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Adverse event reporting additional description |
All SAEs, whether suspected to be related to study treatment or not, are reported by telephone, fax
or e-mail immediately to the responsible Clinical Project Manager, study monitor, or to the
responsible local CRO.
AEs were evalutaed at each patient visit.
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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 |
V15.0
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Reporting groups
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Reporting group title |
all patients exposed to treatment (safety set)
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Reporting group description |
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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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17 Jun 2011 |
Amendment #1: The original study protocol suggested every other day prophylactic treatment with Human-cl rhFVIII for all subjects. After an enrolment period of 6 months it turned out that many patients are not willing to join the study because their doctors and parents prefer a three times weekly injection. The protocol amendment therefore specified that both - every other day treatment as well as three times weekly prophylactic treatment is allowed. |
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07 Oct 2011 |
Amendment #2: The original study protocol was asking for 13 evaluable patients per age cohort to undergo the pharmacokinetic (PK) investigational part of the study. This patient number was based on the EMEA-draft guideline EMEA/CHMP/BPWP/144533/2009, dated 23 July 2009, which requested 13 patients per cohort to be evaluated for the study. On 21. July 2011 the guideline has been finalized, now requesting 12 evaluable patients per age cohort to undergo the PK investigation. The protocol amendment specified that 12 evaluable PK patients per age cohort will be included into the study. |
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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 | |||
