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

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ClinicalTrials.gov Identifier: NCT03376516
Recruitment Status : Active, not recruiting
First Posted : December 18, 2017
Last Update Posted : July 26, 2018
Sponsor:
Information provided by (Responsible Party):
Octapharma

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

Condition or disease Intervention/treatment Phase
Severe Hemophilia A Drug: Wilate Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Clinical Study to Investigate the Pharmacokinetics, Efficacy, Safety, and Immunogenicity of Wilate in Previously Treated Paediatric Patients With Severe Haemophilia A
Actual Study Start Date : November 22, 2017
Estimated Primary Completion Date : November 2018
Estimated Study Completion Date : November 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hemophilia

Arm Intervention/treatment
Experimental: All patients
All patients will receive Wilate for prophylactic treatment. Patients will also receive Wilate for treatment of breakthrough bleeding events as required
Drug: Wilate
von Willebrand factor / Factor VIII (plasma derived)




Primary Outcome Measures :
  1. Area under the curve (AUC) [ Time Frame: 48 h following a single dose of Wilate ]
    Determined using the chromogenic (CHR) and one-stage (OS) assays and actual IMP potencies

  2. FVIII:C area under the curve of FVIII:C normalised for the administered dose (AUCnorm) [ Time Frame: 48 h following a single dose of Wilate ]
    Determined using the chromogenic (CHR) and one-stage (OS) assays and actual IMP potencies

  3. FVIII:C in vivo half-life [ Time Frame: 48 h following a single dose of Wilate ]
    Determined using the chromogenic (CHR) and one-stage (OS) assays and actual IMP potencies

  4. FVIII:C maximum plasma concentration (Cmax) [ Time Frame: 48 h following a single dose of Wilate ]
    Determined using the chromogenic (CHR) and one-stage (OS) assays and actual IMP potencies

  5. FVIII:C time to reach maximum plasma concentration (Tmax) [ Time Frame: 48 h following a single dose of Wilate ]
    Determined using the chromogenic (CHR) and one-stage (OS) assays and actual IMP potencies

  6. Mean residence time (MRT) [ Time Frame: 48 h following a single dose of Wilate ]
    Determined using the chromogenic (CHR) and one-stage (OS) assays and actual IMP potencies

  7. FVIII:C volume of distribution (Vd) [ Time Frame: 48 h following a single dose of Wilate ]
    Determined using the chromogenic (CHR) and one-stage (OS) assays and actual IMP potencies

  8. FVIII:C clearance (CL) [ Time Frame: 48 h following a single dose of Wilate ]
    Determined using the chromogenic (CHR) and one-stage (OS) assays and actual IMP potencies

  9. FVIII:C incremental in vivo recovery (IVR) [ Time Frame: 48 h following a single dose of Wilate ]
    Calculated from FVIII:C plasma levels measured before injection and peak levels obtained in the 15-min post-injection sample using actual IMP potencies


Secondary Outcome Measures :
  1. Total annualised bleeding rate (TABR) [ Time Frame: 6 months ]
    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 periods, will be excluded from the calculation of TABR

  2. Spontaneous annualised bleeding rate (SABR) [ Time Frame: 6 months ]
    Calculated in analogy with the total annualised bleeding rate

  3. Efficacy of Wilate in the treatment of breakthrough BEs based on the proportion of BEs successfully treated with Wilate [ Time Frame: 6 months ]
    At the end of a BE, treatment efficacy will be assessed by the patient (together with the Investigator in case of on-site treatment) using predefined four-point scale: 'excellent', 'good', 'moderate', 'none'. All efficacy ratings assessed as either 'excellent' or 'good' will be considered 'successfully treated.'

  4. Consumption of Wilate for prophylaxis [ Time Frame: 6 months ]
    Calculated as FVIII IU/kg per week per patient

  5. FVIII:C incremental in vivo recovery (IVR) of Wilate over time [ Time Frame: Baseline, and 3 and 6 months of treatment ]
    Calculated from FVIII:C plasma levels measured before injection and peak levels obtained in the 15-min post-injection sample using actual IMP potencies

  6. Association between AB0 blood type and the FVIII:C half-life of Wilate [ Time Frame: 6 months ]
    AB0 blood type will be checked at screening if not known from MH FVIII:C half-life of Wilate determined using both the chromogenic (CHR) and one-stage (OS) assays and actual IMP potencies

  7. Association between VWF:Ag concentration and the FVIII:C half-life of Wilate [ Time Frame: 6 months ]
    For this association VWF:Ag and the FVIII:C half-life of Wilate will be measured within 1 h before injection as well as 15±5 min after the end of injection during the PK visit, at 3 Months visit and 6 Months visits FVIII:C half-life of Wilate determined using both the chromogenic (CHR) and one-stage (OS) assays and actual IMP potencies.

  8. Safety and tolerability of Wilate by monitoring adverse events (AEs) throughout the study [ Time Frame: 6 months ]

    At each visit, whether scheduled or unscheduled, AEs will be elicited using a standard non leading question such as:

    "How have you been since the last visit/during the previous study period?" In addition, the investigator will check the patient diaries for any documented event


  9. Immunogenicity of Wilate by testing for FVIII inhibitors [ Time Frame: 6 months ]
    Blood sample for FVIII inhibitors will be taken at each study visit: screening, PK, Day 14 visit, Day 30 visit, 3 Months visit and 6 Months visit before injection

  10. Virus safety in terms of parvovirus B19 [ Time Frame: 6 months ]
    Blood sample for parvovirus B19 will be taken at screening and at 6 Months visit in case the one at screening is negative



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Ages Eligible for Study:   1 Year to 11 Years   (Child)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03376516


Locations
Russian Federation
Kirov SSC Hematology and Transfusiology
Kirov, Russian Federation
Ukraine
"National Children's Specialized Clinic "OKHMATDYT"
Kyiv, Ukraine
"Western Ukrainian Specialized Children's Medical Center"
Lviv, Ukraine
Sponsors and Collaborators
Octapharma
Investigators
Study Director: Cristina Solomon, MD Octapharma

Responsible Party: Octapharma
ClinicalTrials.gov Identifier: NCT03376516     History of Changes
Other Study ID Numbers: WIL-30
First Posted: December 18, 2017    Key Record Dates
Last Update Posted: July 26, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Factor VIII
Coagulants