Pharmacokinetics, Efficacy, Safety, and Immunogenicity of Wilate in Previously Treated Paediatric Patients With Severe Haemophilia A

NCT03376516 | Completed Phase 3 Results FDA Drug

• 1 other identifier: WIL-30
• Study Type: interventional
• Target: 11
• Locations: 2 countries
• Sites: 3

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

Conditions

Severe Hemophilia A

Outcome Measures

Primary Outcomes (9)

• Pharmacokinetic (PK) Assessment (Area Under the Curve (AUC)) of FVIII:C

  PK assessments of the factor VIII coagulant activity (FVIII:C) for Wilate were determined using the one-stage (OS) assay. The units of measure to calculate AUC is hours (h) x international units (IU)/decilitre (dL).

  0h, 0.25h, 1h, 6h, 24h and 48 h following a single dose of Wilate

• Pharmacokinetic (PK) Assessment (Area Under the Curve [AUC] Normalised (AUCNorm)) of FVIII:C for Wilate

  PK assessments of the factor VIII coagulant activity (FVIII:C) for Wilate were determined using the one-stage (OS) assay. The mean area under the curve normalised for the administered dose (AUCnorm) was calculated for Wilate. The units of measure used were AUC divided by dose.

  0h, 0.25h, 1h, 6h, 24h and 48 h following a single dose of Wilate

• Pharmacokinetic (PK) Assessment (Half-life (h)) of FVIII:C

  PK assessments of the factor VIII coagulant activity (FVIII:C) for Wilate were determined using the one-stage (OS) assay. The units of measure to calculate half-life is hours.

  0h, 0.25h, 1h, 6h, 24h and 48 h following a single dose of Wilate

• Pharmacokinetic (PK) Assessment (Maximum Plasma Concentration) for FVIII:C

  PK assessments of FVIII:C were determined using the one-stage (OS) assays. The maximum plasma concentration of FVIII:C was calculated based on the FVIII:C values measured in the patients participating in the PK study. Units of measure for maximum plasma concentration are international units (IU)/ decilitre (dL)

  0h, 0.25h, 1h, 6h, 24h and 48 h following a single dose of Wilate

• Pharmacokinetic (PK) Assessment (Time to Reach Maximum Plasma Concentration (Tmax)) of FVIII:C

  PK assessments of the factor VIII coagulant activity (FVIII:C) for Wilate were determined using the one-stage (OS) assay. The units of measure to calculate Tmax is hours (h).

  48 h following a single dose of Wilate

• Pharmacokinetic (PK) Assessment (Mean Residence Time (MRT)) of FVIII:C

  PK assessments of the factor VIII coagulant activity (FVIII:C) for Wilate were determined using the one-stage (OS) assay. The units of measure to calculate MRT is hours.

  48 h following a single dose of Wilate

• Pharmacokinetic (PK) Assessment (Volume of Distribution (Vd)) of FVIII:C

  PK assessments of the factor VIII coagulant activity (FVIII:C) for Wilate were determined using the one-stage (OS) assay. The units of measure to calculate Vd is decilitre (dL)/ kilograms (kg).

  0h, 0.25h, 1h, 6h, 24h and 48 h following a single dose of Wilate

• Pharmacokinetic (PK) Assessment (Clearance) of FVIII:C

  PK assessments of the factor VIII coagulant activity (FVIII:C) for Wilate were determined using the one-stage (OS) assay. The units of measure to calculate clearance are decilitre (dL)/ hours (h)/ kilograms (kg).

  0h, 0.25h, 1h, 6h, 24h and 48 h following a single dose of Wilate

• Incremental In Vivo Recovery (IVR) of FVIII:C

  The incremental IVR was determined from all patients at baseline was determined using the one-stage (OS) assay (standardised to 50 IU/kg). The units of measure to calculate IVR is kilograms (kg) / deciliter (dL)

  48 h following a single dose of Wilate

Secondary Outcomes (10)

• Total Annualized Bleeding Rate (TABR)

  6 months

• Spontaneous Annualized Bleeding Rate (SABR)

  6 months

• Efficacy of Wilate in the Treatment of Breakthrough Bleeding Events (BEs)

  6 months

• Wilate Consumption Data: Average Dose of Wilate Per Week of Study

  6 months

• Incremental in Vivo Recovery (IVR) of Wilate Over Time

  Baseline, and 3 and 6 months of treatment

Study Arms (1)

All patients

EXPERIMENTAL

All patients will receive Wilate for prophylactic treatment. Patients will also receive Wilate for treatment of breakthrough bleeding events as required

Drug: Wilate

Interventions

Wilate DRUG

von Willebrand factor / Factor VIII (plasma derived)

All patients

Eligibility Criteria

• Age: 1 Year - 11 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Severe haemophilia A (\<1% FVIII:C) according to medical history
• Male patients aged 1 to \<12 years
• Previous treatment with a FVIII concentrate for at least 50 exposure days (EDs)
• Immunocompetence (CD4+ count \>200/μL)
• 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

You may not qualify if:

• Any coagulation disorders other than haemophilia A
• 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
• Severe liver or kidney diseases (alanine aminotransferase \[ALAT\] and aspartate transaminase \[ASAT\] levels \>5 times of upper limit of normal, creatinine \>120 μmol/L)
• 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

Sponsors & Collaborators

• Octapharma: lead

Study Sites (3)

Kirov SSC Hematology and Transfusiology

Kirov, Russia

Location

"National Children's Specialized Clinic "OKHMATDYT"

Kyiv, Ukraine

Location

"Western Ukrainian Specialized Children's Medical Center"

Lviv, Ukraine

Location

MeSH Terms

Conditions

Hemophilia A

Interventions

von Willebrand Factor

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Biological Factors

Results Point of Contact

• Title: Sylvia Werner
• Organization: Octapharma AG

sylvia.werner@octapharma.com

604-1149

Study Officials

• Cristina Solomon, MD

  Octapharma

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2017
• First Posted: December 18, 2017
• Study Start: November 22, 2017
• Primary Completion: November 3, 2018
• Study Completion: November 3, 2018
• Last Updated: January 19, 2021
• Results First Posted: December 24, 2019

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

RU (1); UA (2)