Prospective clinical study in children with severe haemophilia A to investigate clinical efficacy, immunogenicity, pharmacokinetics, and safety of Human-cl rhFVIII

ISRCTN ISRCTN71212110
DOI https://doi.org/10.1186/ISRCTN71212110
Secondary identifying numbers GENA-03
Submission date
24/01/2011
Registration date
23/02/2011
Last edited
13/12/2017
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Haematological Disorders
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Ms Martina Jansen
Scientific

Oberlaaerstrasse 235
Vienna
1100
Austria

Phone +43 (0)1 61032 1208
Email martina.jansen@octapharma.com

Study information

Study designProspective cross-over (part I) open-label trial
Primary study designInterventional
Secondary study designNon randomised study
Study setting(s)Other
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details to request patient information material
Scientific titleProspective clinical study in children with severe haemophilia A to investigate clinical efficacy, immunogenicity, pharmacokinetics, and safety of Human-cl rhFVIII
Study objectivesInvestigation of efficacy and safety (and pharmacokinetics in 50% of the patients included) of Human-cl rhFVIII in severe haemophilia A children (2 - 12 years old), followed for a 6-month open prophylactic treatment period.

On 03/01/2012 the overall trial end date was changed from 01/12/2011 to 01/10/2012. The countries of recruitment were changed to include Romania and Serbia.
Ethics approval(s)Ethics Committee of Brno, Czech Republic, 23/06/2010, ref: 049/10MEK
Health condition(s) or problem(s) studiedSevere haemophilia A
InterventionThis study schedules two patient groups and two study phases. One patient group passes through both study phases, whereas the other patient group undergoes the second study phase only.

Study phase I ('pharmacokinetic phase') is intended to give information about the pharmacokinetics of Human-cl rhFVIII and is applicable for half of the patients included into this study. Within this phase, patients will visit their study doctor twice for the purpose of a drug administration and subsequent blood collections. The first time, the blood samples will be taken after the injection of the actually used FVIII concentrate, while the other time, the same procedure will be done after Human-cl rhFVIII administration. All patients having completed study phase I are intended to continue with study phase II.

The remaining half having not been included into study phase I, will only partake in the second study phase ('open treatment phase') which is intended to prove the efficacy of a prophylactic six-month treatment with Human-cl rhFVIII. As the need arises, also on demand treatment with Human-cl rhFVIII will be possible. Further aims of this study phase would be to investigate the immunogenic and the safety potential of Human-cl rhFVIII.

Within study phase II, five consultations with the study physician will take place. Three of them will comprehend a blood collection by which an exclusion of inhibitors will be ensured. The remaining two visits are for incremental recovery purposes, meaning that after having taken a reference blood sample, Human-cl rhFVIII will be administered, followed by two further blood sample withdrawals.

In either case the study starts with a Screening Visit, comprehending identical general basic investigations for all patients.
Intervention typeOther
Primary outcome measure1. Efficacy of prophylactic treatment: the frequency of breakthrough bleeds under prophylactic treatment will be calculated. Study drug consumption data (FVIII IU/kg, extrapolated to monthly and yearly usage) both per subject and in total will be evaluated
2. Efficacy of on-demand treatment of breakthrough bleeding episodes
Secondary outcome measures1. Pharmacokinetic parameters: in 50% of the included patients the following pharmacokinetic parameters of Human-cl rhFVIII are determined and compared with the previously used FVIII concentrate: in vivo half-life (T1/2), AUC, Cmax, Tmax, MRT, Vd, and CL. These PK parameters will be calculated for FVIII:C using both the CHR and the OS assays and the actual potency of Human-cl rhFVIII
2. In-vivo recovery: will be calculated - also over time - from the FVIII levels before and peak level obtained in the 0.5 or 2 hours post-infusion samples
3. The immunogenic potential of Human-cl rhFVIII is investigated by controlling the inhibitor titre
4. The efficacy of Human-cl rhFVIII in surgeries is assessed
5. The safety of Human-cl rhFVIII in terms of adverse event monitoring is assessed
Overall study start date01/01/2011
Completion date01/10/2012

Eligibility

Participant type(s)Patient
Age groupChild
Lower age limit2 Years
Upper age limit12 Years
SexMale
Target number of participants60
Key inclusion criteria1. Must have severe haemophilia A (FVIII:C less than 1%; historical value as documented in subject records)
2. Previously treated with FVIII concentrate, at least 50 EDs
3. Immunocompetent (CD4+ count above greater than 200/µL)
4. Human immunodeficiency virus (HIV) negative or respective viral load less than 200 particles/µL or less than 400,000 copies/ml
5. Freely given written informed consent by parents or legal guardian
6. Aged between 2 and 12 years, males only
Key exclusion criteria1. Other coagulation disorder than haemophilia A
2. Present or past FVIII inhibitor activity (greater than 0.6 BU)
3. Target joints
4. Severe liver or kidney disease (alanine aminotranferase [ALAT] and aspartate aminotransferase [ASAT] levels greater than 5 times of upper limit of normal, creatinine greater than 120 µmol/L)
4. Receiving or scheduled to receive immuno-modulating drugs (other than anti-retroviral chemotherapy) such as alpha-interferon, prednisone (equivalent to greater than 10 mg/day), or similar drugs
5. Current participation in another clinical study
6. Participation in another interventional clinical study with administration of investigational medical product (IMP) in the course of the past 3 months, except studies investigating already registered FVIII products
Date of first enrolment01/01/2011
Date of final enrolment01/10/2012

Locations

Countries of recruitment

  • Austria
  • Czech Republic
  • France
  • Germany
  • Poland
  • Romania
  • Russian Federation
  • Serbia
  • Türkiye
  • United Kingdom

Study participating centre

Oberlaaerstrasse 235
Vienna
1100
Austria

Sponsor information

Octapharma AG (Switzerland)
Industry

Seidenstrasse 2
Lachen
CH-8853
Switzerland

Phone +41 (0)55 451 2141
Email sigurd.knaub@octapharma.ch
Website http://www.octapharma.com
ROR logo "ROR" https://ror.org/002k5fe57

Funders

Funder type

Industry

Octapharma AG (Switzerland)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 01/03/2016 Yes No

Editorial Notes

13/12/2017: Publication reference added.