Clinical trial NCT02954575: Clinical Study to Investigate the PK, Efficacy, and Safety of Wilate in Patients With Severe Hemophilia A
Official title: Clinical Study to Investigate the Pharmacokinetics, Efficacy, Safety, and Immunogenicity of Wilate in Previously Treated Patients With Severe Hemophilia A
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Severe Hemophilia A
Lead sponsor: Octapharma
Sponsor class: INDUSTRY
First posted: 2016-11-03
Enrollment: 57
Sex: MALE
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to obtain additional data on the safety and efficacy of Wilate in PTPs with hemophilia A with at least 150 previous exposure days (EDs) to a FVIII concentrate who undergo prophylactic treatment with Wilate for 6 months and at least 50 EDs, thus supplementing the existing database to obtain approval of Wilate for the indication hemophilia A in the USA.


Eligibility 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 preceding study start)
6. Voluntarily given, fully informed written and signed consent obtained by the patient (or parent/legal guardian in case of adolescents) before any study-related procedures 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., exclusion criterion no. 4).

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

Primary outcomes:
measure: Total Annualized Bleeding Rate (TABR)
timeFrame: 6 months
Secondary outcomes:
measure: Spontaneous Annualized Bleeding Rate (SABR)
timeFrame: 6 months
measure: Efficacy of Wilate in the Treatment of Breakthrough BEs
timeFrame: 6 months
measure: Wilate Consumption Data (Average Total Normdose of FVIII IU/kg Per Month of Study) for Prophylaxis
timeFrame: 6 months
measure: Pharmacokinetic (PK) Assessment (Area Under the Curve [AUC] Norm) of FVIII:C
timeFrame: Initial PK visit (Day -1) and PK study completion visit (6 months); data collected 1 h prior to injection and 15 min, 1 h, 3 h, 6 h, 9 h, 24 h, 30 h and 48 h after the end of injection
measure: Pharmacokinetic (PK) Assessment (in Vivo Half-Life (t1/2)) of FVIII:C
timeFrame: Initial PK assessment (Day -1) and PK study completion visit (6 months); data collected 1 h prior to infusion and 15 min, 1 h, 3 h, 6 h, 9 h, 24 h, 30 h and 48 h after the end of injection
measure: Pharmacokinetic (PK) Assessment (Maximum Plasma Concentration [Cmax]) of FVIII:C
timeFrame: Initial PK assessment (Day -1) and 6 months
measure: Incremental in Vivo Recovery (IVR) of Wilate Over Time
timeFrame: Baseline, 3 and 6 months
measure: Association Between ABO Blood Type and the FVIII:C Half-life of Wilate (OS Assay)
timeFrame: 6 months
measure: Association Between VWF:Ag Concentration and the FVIII:C Half-life of Wilate
timeFrame: 6 months
measure: Safety and Tolerability of Wilate by Monitoring Adverse Events (AEs) Throughout the Study
timeFrame: 6 months
measure: Immunogenicity of Wilate by Testing for FVIII Inhibitors
timeFrame: 6 months
measure: Virus Safety Measured by the Number of Parvovirus B19 Seroconversions Between Baseline (BL) and End of Study
timeFrame: 6 months
Other outcomes:
measure: Efficacy of Wilate in Surgical Prophylaxis
timeFrame: 6 months
Locations:
city: Sofia
country: Bulgaria
facility: Specialized Hospital for Active Treatment "Joan Pavel"
city: Budapest
country: Hungary
facility: National Haemophilia Centre
city: Krakow
country: Poland
facility: Krakowskie Centrum Medyczne
city: Rzeszow
country: Poland
facility: Korczowski Bartosz Gabinet Lekarski
city: Bucharest
country: Romania
facility: Centrul Medical Unirea -Policlinica Enescu
city: Barnaul
country: Russian Federation
facility: Barnaul Branch of RAMS hematology center
city: Moscow
country: Russian Federation
facility: Federal Scientific Hematology Center
Study officials:
affiliation: Octapharma
name: Cristina Solomon, MD
role: STUDY_DIRECTOR
References: