Study to Investigate the product Wilate in Patients with Severe Hemophilia A

• Register: EUCTR
• Last refreshed on: 30 April 2018
• Main ID: EUCTR2016-003681-34-HU
• Date of registration: 03/11/2016
• Prospective Registration: Yes
• Primary sponsor: Octapharma AG
• Public title: Study to Investigate the product Wilate in Patients with Severe Hemophilia A
• Scientific title: Clinical Study to Investigate the Pharmacokinetics, Efficacy, Safety, and Immunogenicity of Wilate in Previously Treated Patients with Severe Hemophilia A
• Date of first enrolment: 29/12/2016
• Target sample size: 55
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-003681-34
• 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

Bulgaria, Hungary, Poland, Russian Federation, Serbia, Ukraine, United States

Contacts

• Name: Clinical Trial Manager
• Affiliation: Octapharma AG

• Name: Clinical Trial Manager
• Affiliation: Octapharma AG

Key inclusion & exclusion criteria

Inclusion criteria:
1. Severe hemophilia A (<1% FVIII:C) according to medical history 2. Male patients aged =12 years
3. Previous treatment with a FVIII concentrate for at least 150 exposure days (EDs)
4. Immunocompetence (CD4+ count >200/µL)
5. Good documentation of the historical bleeding rate (at least for the 6 months pre-ceding study start)
6. Voluntarily given, fully informed written and signed consent obtained by the pa-tient (or parent/legal guardian in case of adolescents) before any study-related pro-cedures are conducted
Whenever possible, the interval between the Screening Visit and the PK or Non-PK Visit should not exceed 30 days. If the 30-day interval is exceeded, determination of the CD4+ count is to be repeated and must be >200/µL for patients to be enrolled (i.e., inclusion criterion no. 4).
Are the trial subjects under 18? yes
Number of subjects for this age range: 10
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion criteria:
1. Any coagulation disorders other than hemophilia A
2. History of FVIII inhibitor activity (=0.6 BU) or detectable FVIII inhibitory anti-bodies (=0.6 BU using the Nijmegen modification of the Bethesda assay) at screening, as determined by the central laboratory
3. Severe liver or kidney diseases (alanine aminotransferase [ALAT] and aspartate transaminase [ASAT] levels >5 times of upper limit of normal, creatinine >120 µmol/L)
4. Patients receiving or scheduled to receive immunomodulating drugs (other than anti-retroviral chemotherapy) such as alpha-interferon, prednisone (equivalent to >10 mg/day), or similar drugs
5. Treatment with any investigational medicinal product in another interventional clinical study currently or within 4 weeks before enrollment


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

Health Condition(s) or Problem(s) studied

Severe hemophilia A (<1% FVIII:C)
MedDRA version: 19.1 Level: LLT Classification code 10060613 Term: Hemophilia A (Factor VIII) System Organ Class: 100000004850

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

Intervention(s)

Trade Name: Wilate 500
Product Name: Wilate
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: Wilate
Current Sponsor code: Wilate
Other descriptive name: HUMAN COAGULATION FACTOR VIII, VON WILLEBRAND FACTOR COMPLEX
Concentration unit: IU/ml international unit(s)/millilitre
Concentration type: equal
Concentration number: 500-

Trade Name: Wilate 1000
Product Name: Wilate
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: Wilate
Current Sponsor code: Wilate
Other descriptive name: HUMAN COAGULATION FACTOR VIII, VON WILLEBRAND FACTOR COMPLEX
Concentration unit: IU/ml international unit(s)/millilitre
Concentration type: equal
Concentration number: 1000-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: After the end of the study

Main Objective: The primary objective of this study is to determine the efficacy of Wilate in the prophylactic treatment of previously treated patients (PTP) with severe hemophilia A.

Secondary Objective: • Determine the efficacy of Wilate in the treatment of breakthrough bleeding episodes (BEs)
• Calculate the FVIII:C pharmacokinetics (PK) for Wilate at baseline and after 6 months of prophylactic treatment
• Calculate the FVIII:C incremental IVR of Wilate over time (at baseline, and at 3 and 6 months of treatment)
• Assess the association between AB0 blood type and the FVIII:C halflife of Wilate
• Assess the association between the VWF:Ag concentration and the FVIII:C half-life of Wilate
• Assess the safety and tolerability of Wilate
• Assess the immunogenicity of Wilate
Additional Objective: descriptive efficacy of Wilate in surgical prophylaxis.

Primary end point(s): The primary endpoint of this study is a 50% reduction of the total annualized bleeding rate (TABR) observed in the GENA-01 study, with a total of 58.1 BEs per patient per year.
TABR will be calculated as the total number of BEs in the time period between first dose of IMP and the Study Completion Visit, divided by the duration (in years) between first dose of IMP and the Study Completion Visit. Surgery periods, and BEs occurring within these peri-ods, will be excluded from the calculation of TABR.

Secondary Outcome(s)

Secondary end point(s): 1. Spontaneous annualized bleeding rate (SABR)
2. Efficacy of Wilate in the treatment of breakthrough BEs based on the proportion of BEs successfully treated with Wilate
3. Wilate consumption data (FVIII IU/kg per week per patient) for prophylaxis
4. Baseline PK parameters for FVIII:C using both the chromogenic (CHR) and one-stage (OS) assays and actual IMP potencies
5. Incremental IVR of Wilate over time (at baseline, and at 3 and 6 months of treatment)
6. Association between AB0 blood type and the FVIII:C half-life of Wilate
7. Association between VWF:Ag concentration and the FVIII:C half-life of Wilate
8. Safety and tolerability of Wilate by monitoring adverse events (AEs) throughout the study
9. Immunogenicity of Wilate by testing for FVIII inhibitors
10. Virus safety in terms of parvovirus B19
Exploratory Endpoint: the descriptive efficacy of Wilate in surgical
prophylaxis.

Timepoint(s) of evaluation of this end point: After the end of the study

Secondary ID(s)

WIL-27

Source(s) of Monetary Support

Octapharma AG