Study to collect data to further monitor whether the treatment triggers an immune reaction (i.e. development of antibodies, so called “inhibitors” directed against factor 8), to further investigate how well Human-cl rhFVIII prevents and stops bleeding episodes, and to monitor if it is safe and well tolerated in the treatment on a long-term basis.

• Register: EUCTR
• Last refreshed on: 7 October 2014
• Main ID: EUCTR2013-003997-28-DE
• Date of registration: 29/04/2014
• Prospective Registration: Yes
• Primary sponsor: Octapharma Pharmazeutika Produktionsges.m.b.H.
• Public title: Study to collect data to further monitor whether the treatment triggers an immune reaction (i.e. development of antibodies, so called “inhibitors” directed against factor 8), to further investigate how well Human-cl rhFVIII prevents and stops bleeding episodes, and to monitor if it is safe and well tolerated in the treatment on a long-term basis.
• Scientific title: Extension Study for Patients who completed GENA-05 (NuProtect) – to Investigate Immunogenicity, Efficacy and Safety of Treatment with Human-cl rhFVIII
• Date of first enrolment: 30/07/2014
• Target sample size: 100
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-003997-28
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1

Countries of recruitment

Brazil, Canada, Colombia, France, Georgia, Germany, India, Moldova, Republic of, Morocco, Poland, Russian Federation, Spain, Ukraine, United Kingdom, United States, Venezuela, Bolivarian Republic of

Contacts

• Name: Regulatory Affairs
• Affiliation: inVentiv Health Clinical UK Ltd

• Name: Regulatory Affairs
• Affiliation: inVentiv Health Clinical UK Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
In order to qualify for study enrolment, the following criteria must be fulfilled before study entry:
1. patients who completed GENA-05 in accordance with the study protocol
2. Voluntarily given, fully informed written and signed consent obtained before any study-related procedures are conducted (obtained from the patient’s parent/legal guardian)
Are the trial subjects under 18? yes
Number of subjects for this age range: 100
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion criteria:
Patients will not be included if any of the following exclusion criteria are met:
1. 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);
2. Concomitant treatment with any systemic immunosuppressive drug;
3. Other FVIII concentrate than Human-cl rhFVIII was received between completion visit of GENA-05 and start of GENA-15 (except emergency cases).


Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Severe Haemophilia A
MedDRA version: 17.0 Level: LLT Classification code 10018938 Term: Haemophilia A (Factor VIII) System Organ Class: 100000004850

Intervention(s)

Product Name: Human cell line recombinant factor VIII
Product Code: Human-cl rhFVIII
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: Human-cl rhFVIII
CAS Number: N.A
Current Sponsor code: 140
Other descriptive name: Human Coagulation Factor VIII
Concentration unit: IU international unit(s)
Concentration type: range
Concentration number: 250-2000

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: • At Screening Visit, which will most likely be the same sampling time-point as the completion visit of GENA-05
• Once every 6 months in the course of the follow-up visits
• At study completion
• Any time in the case of a suspicion of inhibitor development.

Primary end point(s): Immunogenicity of Human-cl rhFVIII is the primary endpoint.
Inhibitor activity will be determined by the modified Bethesda assay (Nijmegen modification), using congenital FVIII-deficient human plasma, spiked with Human-cl rhFVIII. In case of a positive inhibitor result, an inhibitor retesting, using a second separately drawn sample, should be performed. A FVIII inhibitor is defined as “positive”, if the retesting confirms the positive result, otherwise the result is considered as “negative”.

Main Objective: • To investigate the immunogenicity of Human-cl rhFVIII in patients who
completed GENA-05 in accordance with the study protocol
• To assess the efficacy of Human-cl rhFVIII during prophylactic treatment (based
on the frequency of spontaneous break-through bleeds)
• To assess the efficacy of Human-cl rhFVIII during treatment of bleeds
• To assess the efficacy of Human-cl rhFVIII in surgical prophylaxis
• To assess the safety and tolerability of Human-cl rhFVIII

Secondary Objective: not applicable

Secondary Outcome(s)

Secondary end point(s): 1. Efficacy:
a.Efficacy of prophylactic treatment
The efficacy of Human-cl rhFVIII in the prophylactic treatment will be investigated by calculating the frequency of spontaneous break-through bleeds under prophylactic treatment. Study drug consumption data (FVIII IU/kg per month, per year) per patient and in total will be evaluated. The dates and times of study drug infusions, the details of dose(s), and the product batch numbers used for the prophylactic treatment will be documented.
b. Efficacy of treatment of bleeds
The efficacy of Human-cl rhFVIII in the treatment of bleeds will be investigated by using a 4-point ordinal haemostatic efficacy scale. Details of the bleed, the amount of Human-cl rhFVIII needed and the number of injections necessary to stop the bleed will be documented.
c. Efficacy of surgical prophylaxis
In surgical procedures, the following parameters will be documented:
• One overall efficacy assessment (taking into account the intra- and post-operative assessment) after the end of surgical prophylactic treatment phase, agreed upon between the surgeon and the haematologist.
• Average and maximum expected estimated blood loss, compared to the actual estimated blood loss
• Details on surgical procedure: location, severity, type, expected and
actual duration
• Pre-, intra-, and post-operative FVIII plasma levels, if appropriate
• Details of administered dose(s) of Human-cl rhFVIII given pre-, intra- and/or postoperatively including dates, times and batch numbers
• Details on concomitantly administered drugs, including all blood and blood product transfusions, excluding standard anaesthetic drugs
• Details on all wound haematomas in terms of capturing, analysing, and reporting these, including any need for surgical evacuation
• Outcome of the intervention, described by means of a brief narrative.

2.Safety
Safety and tolerability will be assessed by monitoring vital signs, standard laboratory parameters, and by monitoring adverse events (AEs).

Timepoint(s) of evaluation of this end point: 1)Efficacy
For each patient, the exposure to Human-cl rhFVIII, the efficacy of Human-cl rhFVIII in the prevention and the treatment of bleeds, the frequency of break-through bleeds in case of prophylactic treatment, the efficacy in surgical prophylaxis, and the overall safety and tolerability of Human-cl rhFVIII will be thoroughly assessed. In the course of the follow-up visits scheduled to be performed every 6 months (± 2 weeks) after the Screening Visit, FVIII
inhibitor levels will be assessed for each patient.
Please refer to section 7.2.2 [Assessments for Secondary Endpoints] on page 30-34 of Protocol

Secondary ID(s)

2013-003997-28-GB

BB-IND 13722

GENA-15

Source(s) of Monetary Support

Octapharma Pharmazeutika Produktions GmbH,