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Completed

NCT Number: NCT02954575

Clinical Study to Investigate the PK, Efficacy, and Safety of Wilate in Patients With Severe Hemophilia A

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.

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Key information

Conditions

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

Age range

12 year and older

Sex eligibility

Male

Study type

Interventional

Phase

Phase 3

Primary location

Specialized Hospital for Active Treatment "Joan Pavel", Sofia, Bulgaria

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Severe hemophilia A (<1% FVIII:C) according to medical history
  • Male patients aged ≥12 years
  • Previous treatment with a FVIII concentrate for at least 150 exposure days (EDs)
  • Immunocompetence (CD4+ count >200/µL)
  • Good documentation of the historical bleeding rate (at least for the 6 months preceding study start)
  • 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

  • Any coagulation disorders other than hemophilia A
  • 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
  • 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 anti-retroviral chemotherapy) such as alpha-interferon, prednisone (equivalent to >10 mg/day), or similar drugs
  • Treatment with any investigational medicinal product in another interventional clinical study currently or within 4 weeks before enrollment

Treatment and study plan

Wilate

Drug

Other names: von Willebrand factor / Factor VIII (plasma derived)

Primary outcomes

  1. Total Annualized Bleeding Rate (TABR)

    Time frame: 6 months

    The total number of bleeding events (BEs) was documented by patients in a patient diary (together with the investigator in case of on-site treatments), which was reviewed at each follow-up visit by site personnel.

Secondary outcomes

  1. Spontaneous Annualized Bleeding Rate (SABR)

    Time frame: 6 months

    The number of spontaneous bleeding events (BEs) was documented by patients in a patient diary (together with the investigator in case of on-site treatments), which was reviewed at each follow-up visit by site personnel.

  2. Efficacy of Wilate in the Treatment of Breakthrough BEs

    Time frame: 6 months

    The proportion of BEs successfully treated with Wilate were documented by the patient (together with the investigator in case of on-site treatments) in the patient diary for all BEs according to a 4-point hemostatic efficacy scale including the four items: 'excellent,' 'good,' moderate,' and 'none', where 'excellent' was defined as "Abrupt pain relief and/or unequivocal improvement in objective signs of bleeding within approximately 8 hours after a single injection" (best outcome) and 'none' was defined as "No improvement within 12 hours, or worsening of symptoms, requiring more than two injections for complete resolution" (worst outcome). All efficacy ratings assessed as either 'excellent' or 'good' were considered 'successfully treated.'

  3. Wilate Consumption Data (Average Total Normdose of FVIII IU/kg Per Month of Study) for Prophylaxis

    Time frame: 6 months

    The average consumption of Wilate per month of study (IU/kg) for all patients receiving prophylaxis.

  4. Pharmacokinetic (PK) Assessment (Area Under the Curve [AUC] Norm) of FVIII:C

    Time frame: 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

    PK assessments of FVIII:C were conducted using the one-stage (OS) assay. The value of the AUCnorm of FVIII:C was calculated based on the FVIII:C values measured in the patients participating in the PK study.

  5. Pharmacokinetic (PK) Assessment (in Vivo Half-Life (t1/2)) of FVIII:C

    Time frame: 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

    PK assessments of FVIII:C were conducted using the one-stage (OS) assay. The in vivo half-life of FVIII:C was calculated based on the FVIII:C values measured in the patients participating in the PK study.

  6. Pharmacokinetic (PK) Assessment (Maximum Plasma Concentration [Cmax]) of FVIII:C

    Time frame: Initial PK assessment (Day -1) and 6 months

    PK assessments of FVIII:C were conducted using the one-stage (OS) assay. The maximum plasma concentration of FVIII:C was calculated based on the FVIII:C values measured in the patients participating in the PK study.

  7. Incremental in Vivo Recovery (IVR) of Wilate Over Time

    Time frame: Baseline, 3 and 6 months

    The rise in FVIII activity in IU/dl per unit dose administered in IU/kg was determined from all patients at baseline, 3 and 6 months, using the OS assay.

  8. Association Between ABO Blood Type and the FVIII:C Half-life of Wilate (OS Assay)

    Time frame: 6 months

    Analysis of variance (ANOVA) was used in an exploratory sense to assess an association between ABO blood type and the FVIII:C half-life of Wilate. This was analyzed by calculating the mean square in a one-stage assay.

  9. Association Between VWF:Ag Concentration and the FVIII:C Half-life of Wilate

    Time frame: 6 months

    ANOVA was used in an exploratory sense to assess an association between VWF:Ag with the FVIII:C half-life of Wilate. This was analyzed by calculating the mean square in a one-stage assay.

  10. Safety and Tolerability of Wilate by Monitoring Adverse Events (AEs) Throughout the Study

    Time frame: 6 months

    At each (scheduled or unscheduled) study visit, AEs were documented by the investigator throughout the study.

  11. Immunogenicity of Wilate by Testing for FVIII Inhibitors

    Time frame: 6 months

    FVIII inhibitor activity was determined at each study visit before the injection of Wilate using the modified Bethesda assay (Nijmegen modification).

  12. Virus Safety Measured by the Number of Parvovirus B19 Seroconversions Between Baseline (BL) and End of Study

    Time frame: 6 months

    Virus safety was evaluated by taking a plasma sample for parvovirus B19 antibody testing before the first injection of Wilate. All patients negative at screening were tested again at the study completion visit. The number with Parvovirus B19 seroconversions between BL and end of study was recorded.

Other outcomes

  1. Efficacy of Wilate in Surgical Prophylaxis

    Time frame: 6 months

    Hemostatic efficacy was assessed at the end of surgery by the surgeon and at end of the postoperative period by the hematologist, using a 4-point hemostatic efficacy scale including the four items: 'excellent' (best possible outcome), 'good', 'moderate' and 'none' (worst outcome). Overall efficacy was assessed by the investigator, taking both the intra and postoperative assessments into account, and using the 'excellent,' 'good,' moderate,' and 'none' scale.

Sponsors and collaborators

Lead sponsor

Octapharma

Industry

Registry information

Official study title

Clinical Study to Investigate the Pharmacokinetics, Efficacy, Safety, and Immunogenicity of Wilate in Previously Treated Patients With Severe Hemophilia A

Important dates

Study start
2016
Primary completion
2018
Study completion
2018
First posted
Nov 3, 2016
Registry last updated
Jan 19, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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