The ability to induce an immune response, efficacy and safety of treatment with Human-cl rhFVIII in previously Untreated Patients ,affected by inherited gender-related coagulation disorder ,in which affected males do not produce functional coagulation factor VIII (FVIII) in sufficient quantities to achieve satisfactory blood clotting.

• Register: EUCTR
• Last refreshed on: 24 January 2022
• Main ID: EUCTR2012-002554-23-SI
• Date of registration: 08/12/2014
• Prospective Registration: Yes
• Primary sponsor: OCTAPHARMA AG
• Public title: The ability to induce an immune response, efficacy and safety of treatment with Human-cl rhFVIII in previously Untreated Patients ,affected by inherited gender-related coagulation disorder ,in which affected males do not produce functional coagulation factor VIII (FVIII) in sufficient quantities to achieve satisfactory blood clotting.
• Scientific title: Immunogenicity, Efficacy and Safety of Treatment with Human-cl rhFVIII in Previously Untreated Patients with Severe Haemophilia A
• Date of first enrolment: 24/02/2015
• Target sample size: 100
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-002554-23
• 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
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belarus, Brazil, Canada, Colombia, Croatia, France, Georgia, Germany, India, Italy, Moldova, Republic of, Poland, Portugal, Russian Federation, Slovenia, 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. Male patients
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 given before any study related procedures are conducted (obtained from the patient’s parent(s)/legal guardian(s))
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. Diagnosis of a coagulation disorder other than haemophilia A
2. Severe liver or kidney disease (ALT or AST levels >5 times of upper limit of normal (ULN), 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


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: 19.0 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 baseline (Screening Visit)
• Every 3-4 EDs until ED 20
• Every 10-12 EDs or every 3 months ± 2 weeks (whichever comes first) after ED 20 until 100 EDs are reached
• Any time in the case of suspicion of an inhibitor development

Secondary Objective: • 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

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 FVIIIdeficient 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 being “negative”.

Main Objective: To investigate the immunogenicity of Human-cl rhFVIII in 100 PUPs suffering from severe haemophilia A (FVIII:C < 1%).

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1)Efficacy
In the prevention and the treatment of bleeds, the frequency of break-through bleeds in case of prophylactic treatment, the efficacy in surgical prophylaxis of Human-cl rhFVIII will be thoroughly assessed. In the course of the follow-up visits (i.e. every 3-4 EDs until ED 20, then every 10-12 EDs until ED 100), scheduled to be performed after the Screening Visit, FVIII inhibitor levels will be assessed.
These visits may be combined with the additional regular 3 monthly (± 2 weeks) follow-up visits.
2) Safety
AEs and changes in concomitant medication, overall safety and tolerability will be checked and documented at each follow-up visit.

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:
• Overall efficacy assessment (taking into account the intra- and post-operative assessment) after the end of surgical prophylactic treatment phase, performed by the surgeon and by 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).

Secondary ID(s)

2012-002554-23-GB

GENA-05

Source(s) of Monetary Support

OCTAPHARMA AG

Ethics review

Status: Approved
Approval date: 16/02/2015
Contact:

Results

• Results available: Yes
• Date Posted: 23/08/2020
• Date Completed: 24/03/2020
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-002554-23/results