Clinical trial NCT03376516: Pharmacokinetics, Efficacy, Safety, and Immunogenicity of Wilate in Previously Treated Paediatric Patients With Severe Haemophilia A
Official title: Clinical Study to Investigate the Pharmacokinetics, Efficacy, Safety, and Immunogenicity of Wilate in Previously Treated Paediatric Patients With Severe Haemophilia A
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Severe Hemophilia A
Lead sponsor: Octapharma
Sponsor class: INDUSTRY
First posted: 2017-12-18
Enrollment: 11
Sex: MALE
Minimum age (years): 1
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A prospective, non-controlled, international, multi-centre phase 3 study to investigate the pharmacokinetics, efficacy, safety, and immunogenicity of Wilate in previously treated children with severe haemophilia A


Eligibility criteria: Inclusion Criteria:

1. Severe haemophilia A (\<1% FVIII:C) according to medical history
2. Male patients aged 1 to \<12 years
3. Previous treatment with a FVIII concentrate for at least 50 exposure days (EDs)
4. Immunocompetence (CD4+ count \>200/μL)
5. Voluntarily given, fully informed written and signed consent obtained by the patient's parent(s) or legal guardian and, depending on the children's developmental stage and intellectual capacity, informed assent by the patients before any study-related procedures are performed

The interval between the Screening Visit and the 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).

Exclusion Criteria:

1. Any coagulation disorders other than haemophilia A
2. History of FVIII inhibitor activity (≥0.6 BU) or detectable FVIII inhibitory antibodies (≥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 antiretroviral chemotherapy), such as alpha-interferon, prednisone (equivalent to \>10 mg/day), or similar drugs

Primary outcomes:
measure: Pharmacokinetic (PK) Assessment (Area Under the Curve (AUC)) of FVIII:C
timeFrame: 0h, 0.25h, 1h, 6h, 24h and 48 h following a single dose of Wilate
measure: Pharmacokinetic (PK) Assessment (Area Under the Curve [AUC] Normalised (AUCNorm)) of FVIII:C for Wilate
timeFrame: 0h, 0.25h, 1h, 6h, 24h and 48 h following a single dose of Wilate
measure: Pharmacokinetic (PK) Assessment (Half-life (h)) of FVIII:C
timeFrame: 0h, 0.25h, 1h, 6h, 24h and 48 h following a single dose of Wilate
measure: Pharmacokinetic (PK) Assessment (Maximum Plasma Concentration) for FVIII:C
timeFrame: 0h, 0.25h, 1h, 6h, 24h and 48 h following a single dose of Wilate
measure: Pharmacokinetic (PK) Assessment (Time to Reach Maximum Plasma Concentration (Tmax)) of FVIII:C
timeFrame: 48 h following a single dose of Wilate
measure: Pharmacokinetic (PK) Assessment (Mean Residence Time (MRT)) of FVIII:C
timeFrame: 48 h following a single dose of Wilate
measure: Pharmacokinetic (PK) Assessment (Volume of Distribution (Vd)) of FVIII:C
timeFrame: 0h, 0.25h, 1h, 6h, 24h and 48 h following a single dose of Wilate
measure: Pharmacokinetic (PK) Assessment (Clearance) of FVIII:C
timeFrame: 0h, 0.25h, 1h, 6h, 24h and 48 h following a single dose of Wilate
measure: Incremental In Vivo Recovery (IVR) of FVIII:C
timeFrame: 48 h following a single dose of Wilate
Secondary outcomes:
measure: Total Annualized Bleeding Rate (TABR)
timeFrame: 6 months
measure: Spontaneous Annualized Bleeding Rate (SABR)
timeFrame: 6 months
measure: Efficacy of Wilate in the Treatment of Breakthrough Bleeding Events (BEs)
timeFrame: 6 months
measure: Wilate Consumption Data: Average Dose of Wilate Per Week of Study
timeFrame: 6 months
measure: Incremental in Vivo Recovery (IVR) of Wilate Over Time
timeFrame: Baseline, and 3 and 6 months of treatment
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 The Number of Adverse Events (AEs) Throughout the Study
timeFrame: 6 months
measure: Immunogenicity of Wilate: Number of Participants With FVIII Inhibitor Activity at 6 Months
timeFrame: 6 months
measure: Virus Safety Measured by the Number With Parvovirus B19 Seroconversions Between Baseline (BL) and End of Study
timeFrame: 6 months
Other outcomes:
Locations:
city: Kirov
country: Russian Federation
facility: Kirov SSC Hematology and Transfusiology
city: Kyiv
country: Ukraine
facility: "National Children's Specialized Clinic "OKHMATDYT"
city: Lviv
country: Ukraine
facility: "Western Ukrainian Specialized Children's Medical Center"
Study officials:
affiliation: Octapharma
name: Cristina Solomon, MD
role: STUDY_DIRECTOR
References: