NuProtect: Immunogenicity, efficacy and safety of treatment with Human-cl rhFVIII in previously untreated patients with severe haemophilia A

ISRCTN ISRCTN50040185
DOI https://doi.org/10.1186/ISRCTN50040185
EudraCT/CTIS number 2012-002554-23
ClinicalTrials.gov number NCT01712438
Secondary identifying numbers GENA-05
Submission date
11/09/2013
Registration date
22/10/2013
Last edited
23/05/2022
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

Background and study aims
FVIII concentrates are the only available treatment for patients with severe haemophilia A. However, patients are at risk of developing resistance (inhibitor) to FVIII, which stops the treatment from working, and patients may also suffer from an allergic reaction. The drug under investigation, human-cl rhFVIII, is a newly developed recombinant FVIII concentrate from a human cell line, which may have less immunogenic potential (ability to provoke an immune response) compared to FVIII concentrates from hamster cell lines or plasma-derived FVIII concentrates. The main aim of the study is to investigate the immunogenicity of the new product in previously untreated patients with severe haemophilia A. This population is at the highest risk of developing inhibitors. Previous studies of the new product in already treated patients (adults and children) did not show a single case of inhibitor development.

Who can participate?
Previously untreated patients with severe haemophilia A.

What does the study involve?
All patients will receive the newly developed recombinant FVIII concentrate injection. The study involves regular blood sampling to screen for inhibitors. All patients’ adverse events are documented.

What are the possible benefits and risks of participating?
Human-cl rhFVIII may have less immunogenic potential compared to recombinant FVIII concentrates from hamster cell lines or plasma-derived FVIII concentrates. However, as for all FVIII concentrates, patients are at risk of developing an inhibitor to FVIII and may suffer from an allergic reaction.

Where is the study run from?
The study is planned to be conducted at about 45 study sites in 16 countries worldwide.

When is the study starting and how long is it expected to run for?
The study started in March 2013, and is planned to be completed in 2018.

Who is funding the study?
Octapharma AG, Switzerland

Who is the main contact?
Martina Jansen
Octapharma PPG
Clinical Research & Development Haematology
Oberlaaerstrasse 235
1100 Vienna, Austria

Contact information

Dr Raina Liesner
Scientific

Great Ormond Street Hospital for Children, NHS Trust
Haemophilia Centre
Great Ormond Street
London
WC1N 3JH
United Kingdom

Study information

Study designProspective multicentre multinational open-label non-controlled study
Primary study designInterventional
Secondary study designNon randomised study
Study setting(s)Hospital
Study typeScreening
Participant information sheet Not available in web format, please use the contact details below to request a patient information sheet
Scientific titleImmunogenicity, efficacy and safety of treatment with Human-cl rhFVIII in previously untreated patients with severe haemophilia A: a prospective, multinational, open-label, non-controlled study
Study objectivesImmunogenicity of Human-cl rhFVIII in previously untreated patients with severe haemophilia A is low.
Ethics approval(s)Canada, HIREB Hamilton: 11 March 2013
Germany, Ethics Committee University Münster: 08 July 2013
Spain, Vall d`Hebron, Barcelona: 11 January 2013
France, CPP Ouest V, Nanterre: 07 February 2013
UK, NRES Committee London-Central: 19 February 2013
Georgia, Committee of Institute of Haematology, Tiflis: 17 January 2013
Moldova, National Ethics Committee, Chisinau: 29 January 2013
Poland, EC Medical University Warsaw: 12 February 2013
Russia, Izmailowska EC: 26 June 2013
Ukraine, National Academy of Medical Science: 04 February 2013
Health condition(s) or problem(s) studiedSevere haemophilia A
InterventionThere is only one study arm. All patients receive the same investigational medicinal product (IMP) intravenously. The dose, frequency and duration are flexible, and depend on the individual clinical condition of the patient.
Intervention typeDrug
Pharmaceutical study type(s)
PhasePhase III
Drug / device / biological / vaccine name(s)Human-cl rhFVIII
Primary outcome measureThe immunogenic potential of the IMP. Each patient is tested for the development of inhibitors at treatment start, every three to four exposure days to the IMP, latterly every ten exposure days (latest every three months).
Secondary outcome measuresSafety, efficacy and tolerability: Efficacy (by assessing each treatment of a bleeding episode, or the rate of bleeds in case of prophylactic treatment) and safety (adverse events) are observed during the entire study duration, which is planned for a total of 100 exposure days with the IMP, but not longer than 5 years.
Overall study start date01/03/2013
Completion date24/03/2020

Eligibility

Participant type(s)Patient
Age groupChild
SexMale
Target number of participants100
Key inclusion criteria1. Male, no age limitations, but due to the required patient population it can be expected that the majority of patients going to be included are babies and small children.
2. Severe haemophilia A (FVIII:C < 1%)
3. No previous treatment with FVIII concentrates or other blood products containing FVIII
4. Voluntarily given, fully informed written and signed consent obtained before any study-related procedures are conducted (obtained from the patient’s parent/legal guardian)
Key exclusion criteria1. Diagnosis with a coagulation disorder other than haemophilia A
2. Severe liver or kidney disease (alanine amino transferase (ALT) or aspartate transaminase (AST) levels >5 times of upper limit of normal, creatinine >120 µmol/L)
3. Concomitant treatment with any systemic immunosuppressive drug
4. Participation in another interventional clinical study currently or during the past 4 weeks.
Date of first enrolment01/03/2013
Date of final enrolment30/06/2016

Locations

Countries of recruitment

  • Brazil
  • Canada
  • Colombia
  • England
  • France
  • Georgia
  • Germany
  • India
  • Moldova
  • Morocco
  • Poland
  • Russian Federation
  • Spain
  • Ukraine
  • United Kingdom
  • United States of America
  • Venezuela

Study participating centre

Great Ormond Street Hospital for Children, NHS Trust
London
WC1N 3JH
United Kingdom

Sponsor information

Octapharma AG (Switzerland)
Industry

Seidenstrasse 2
Lachen
8853
Switzerland

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 planNot provided at time of registration

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Interim results article interim results 01/03/2018 14/05/2019 Yes No
Basic results EU Clinical Trials Register results 23/08/2020 20/05/2022 No No
Basic results ClinicalTrials.gov results 21/10/2019 23/05/2022 No No

Editorial Notes

23/05/2022: ClinicalTrials.gov results added.
20/05/2022: EU Clinical Trials Register results added.
23/04/2020: The overall end date was changed from 31/12/2018 to 24/03/2020.
14/05/2019: Publication reference added.
15/03/2018: The recruitment end date was changed from 31/12/2018 to 30/06/2016.