Clinical study in which the long term effect of Human-cl rhFVIII is investigated in children with severe haemophilia A, who were previously treated in the GENA-03 study

ISRCTN	ISRCTN99606748
DOI	https://doi.org/10.1186/ISRCTN99606748
Protocol serial number	GENA-13
Sponsor	Octapharma AG (Switzerland)
Funder	Octapharma AG (Switzerland)

Submission date: 30/12/2011
Registration date: 03/01/2012
Last edited: 13/03/2020

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
When you cut yourself substances in the blood called clotting factors help the blood to clot. Haemophilia A is an inherited condition in which affected males do not produce enough of the clotting factor FVIII, so they have an increased tendency to bleed. Most bleeding occurs in joints and muscles. Without treatment this bleeding leads to long-term illness with severe disability. The aim of this study is to investigate the long-term effectiveness of giving clotting factor FVIII to previously treated children with severe haemophilia A.

Who can participate?
2 – 13 year old boys and girls with severe haemophilia A who completed the previous GENA-03 study.

What does the study involve?
All patients are injected with FVIII three times a week or every other day depending on their clinical needs. In case of bleeding or surgery further injections may be needed. The effectiveness of the treatment is evaluated every 6 months.

What are the possible benefits and risks of participating?
Based on previous clinical use, FVIII is expected to be safe and effective in the prevention and treatment of bleeding and during surgery. The following side effects may also occur: hypersensitivity or allergic reactions, swelling, burning and stinging at the injection site, chills, flushing, rash, headache, low blood pressure, tiredness, feeling sick, restlessness, rapid heart rate, chest tightness, tingling, vomiting, and wheezing. Rarely, such reactions may progress to the point of severe allergic reaction including shock and fever. However, all patients included into this study had been treated with FVIII for at least 6 months already, and none of these side effects were expected.

Where is the study run from?
The study will be conducted in around 10 sites all over Europe, lead by Great Ormond Street Hospital (UK).

When is the study starting and how long is it expected to run for?
October 2011 to March 2014.

Who is funding the study?
Octapharma AG (Switzerland).

Who is the main contact?
Martina Jansen
martina.jansen@octapharma.com

Contact information

Dr Raina Liesner
Scientific

Haemophilia Comprehensive Care Centre
Level 5, Royal London Hospital for Integrated Medicine (RLHIM)
Great Ormond Street Hospital
Great Ormond Street
London
WC1N 3JH
United Kingdom

Study information

Primary study design	Observational
Study design	Prospective open-label trial
Secondary study design	Cohort study
Study type	Participant information sheet
Scientific title	Clinical study in which the immunogenicity, tolerability and efficacy of Human-cl rhFVIII is investigated in children with severe haemophilia A, who were previously treated in the GENA-03 study
Study objectives	Investigation of long-term efficacy and safety of Human-cl rhFVIII in children with severe haemophilia A (2 - 13 years old), followed up for an open prophylactic treatment until product registration. Follow up to http://www.isrctn.com/ISRCTN71212110
Ethics approval(s)	1. National Research Ethics Service, Riverside, Brighton (UK), 27/09/2011, ref 11/LO/1159 2. University Hospital Brno Ethics Committee, (Czech Republic), 24/08/2011 ref: GENA-13 3. Bioethics Committee, Medical University of Warsaw (Poland), 20/09/2011, ref KB/157/2011 4. People Protection Committee, Paris [Ile de France II] (France), 05/10/2011, ref 2011-08-02
Health condition(s) or problem(s) studied	Severe haemophilia A in children
Intervention	There is just one treatment arm: prophylactic treatment with rFVIII. The investigational medicinal product (IMP) name is Human-cl rhFVIII, which is a recombinant factor 8 concentrate from a human cell-line. The product is injected every other day or three times a week (depending on the clinical needs of the patient), at a prophylactic dose of 30 - 40 IU/kg bodyweight. The study will continue until the patients can switch to the registered and launched product. The expected duration of the individual treatment is at least 2 years.
Intervention type	Biological/Vaccine
Phase
Drug / device / biological / vaccine name(s)
Primary outcome measure(s)	Long-term immunogenicity: Inhibitor activity will be determined by the modified Bethesda assay (Nijmegen modification) using congenital FVIII-deficient human plasma spiked with Human-cl rhFVIII as a test base, at tri-monthly intervals until study completion. At the same time-points, anti-rhFVIII antibodies will be measured. These parameters will also be determined in case inhibitor development is suspected. Sampling for inhibitor and antibody measurements should be performed not less than 48 hours after the previous administration of any FVIII product, if possible. In case of positive inhibitor results, an inhibitor retesting using a second separately drawn sample should be performed. Long-term clinical tolerability: Will be assessed by monitoring Adverse Events (AEs) throughout the study duration.
Key secondary outcome measure(s)	1. Efficacy of prophylactic treatment: Efficacy is to be assessed by evaluating the number of spontaneous breakthrough BEs, as well as by collecting data regarding frequency of IMP injections and regarding the prophylactic IMP doses needed. Overall study drug consumption data (FVIII (IU/kg), per month and per year), per subject and in total, will be analysed. All efficacy ratings having been assessed as 'excellent' and 'good' will be reported as 'successfully treated'. The proportion of BEs successfully treated with Human-cl rhFVIII will be evaluated both for all BEs, as well as broken down to BEs of different severity. 2. Efficacy of surgical prophylaxis: Efficacy will be assessed by the surgeon at the end of surgery (i.e. after last suture), and postoperatively (i.e. at date of discharge or on postoperative day 6, whichever occurs later), by both the surgeon and the haematologist using predefined study criteria, namely 'excellent', 'good', 'moderate' or 'none'. All efficacy ratings of surgical procedures having been assessed 'excellent' and 'good' will be reported as 'successfully treated'.
Completion date	31/03/2014

Eligibility

Participant type(s)	Patient
Age group	Child
Sex	All
Target sample size at registration	60
Key inclusion criteria	1. Evaluable completion of the preceeding study GENA-03 by having a study participation period of 6 months, provided that prophylaxis with Human-cl rhFVIII is continued without intermediate interruption 2. Voluntarily given, fully informed written and signed consent obtained from the parents (or legal guardians) before any study-related procedures are conducted. The need for obtaining assent will depend on the subjects' developmental stage and intellectual capacity 3. Capability to understand and comply with the relevant aspects of the study
Key exclusion criteria	1. Development of FVIII inhibitors (³0.6 Bethesda Units [BU]) in the course of the GENA-03 study 2. Any severe liver or kidney disease (ALT and AST levels >5 times of upper limit of normal, creatinine >120 µmol/L)
Date of first enrolment	31/10/2011
Date of final enrolment	31/03/2014

Locations

Countries of recruitment

United Kingdom
England
Czech Republic
France
Poland
Russian Federation
Türkiye

Study participating centre

Great Ormond Street Hospital

London
WC1N 3JH
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not 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
HRA research summary			28/06/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

13/03/2020: Internal review.
07/03/2018; Publication reference added.
29/01/2018: No publications found,verifying study status with principal investigator.