Clinical Trial: A Trial Investigating Safety and Efficacy of Treatment With BAY94-9027 in Severe Hemophilia A

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Phase II/III, Multicenter, Partially Randomized, Open Label Trial Investigating Safety and Efficacy of On-demand and Prophylactic Treatment With BAY94-9027 in Severe Hemophilia

Brief Summary:

Haemophilia A is an inherited disorder in which one of the proteins, Factor VIII, needed to form blood clots is missing or not present in sufficient levels. In a person with haemophilia A, the clotting process is slowed and the person experiences bleeds that can result in serious problems and potential disability.

The current standard treatment for severe haemophilia A is regularly scheduled infusion of FVIII to keep levels high enough to prevent bleeding. Due to the short half-life of FVIII, prophylaxis may require treatment as often as every other day.

In this trial safety and efficacy of a long-acting recombinant factor VIII molecule is evaluated in subjects with severe Hemophilia A.

120-140 patients will receive open label treatment with long-acting rFVIII either on-demand to treat bleeds or prophylactically for 36 weeks in the main trial plus an optional extension to continue treatment for at least 100 total exposure days (ED). Patients on prophylactic treatment will receive study drug at dosing intervals between once and twice a week depending on their observed bleeding. Patients will attend the treatment centre for routine blood samples and be required to keep an electronic diary.

Male patients aged 12-65, with severe hemophilia A, previously treated with FVIII for at least 50 exposure days may be eligible for this study.


Detailed Summary:

Subjects in prophylactic treatment arms will undergo clinical evaluation at 10 weeks. Those with adequate control of bleeding will undergo randomization to every 5 or 7 day infusion. Those with continued bleeding will remain in treatment arm and have an increase in dose.

Part B-major surgery - optional sub study included to collect information on efficacy of BAY94-9027 in major surgical setting. Due to rarity of surgery in this population, enrollment to this sub-study may be independent of participation in main study.


Sponsor: Bayer

Current Primary Outcome: Annualized Number of Total Bleeds in On-demand Treatment arm (Weeks 0-36) and Prophylaxis arm (Weeks 10 - 36, excluding rescue bleeds) - Part A [ Time Frame: On-demand: Weeks 0 -36 and Prophylaxis: Weeks 10 - 36 during Part A ]

Annualized number of total bleeds was defined as the annualized sum of spontaneous bleeds and trauma bleeds.


Original Primary Outcome: Annualized number of total bleeds [ Time Frame: In the period of 32 weeks after Baseline ]

Current Secondary Outcome:

  • Physician's Assessment of Adequacy of Hemostasis in Major Surgery -Part B [ Time Frame: Baseline up to 6 weeks during Part B ]
    Major surgery was defined as any surgical or invasive procedure (elective or emergent) in which the overall bleeding risk was excessive, required a general anesthetic in an individual without a bleeding disorder, penetrated or exposed a major body cavity, resulted in substantial impairment of physical or physiological functions, or required special anatomic knowledge or manipulative skill. Adequacy of hemostasis was assessed as excellent, good, Moderate or poor, by the Physician during Part B of the study. No subjects were assessed as moderate or poor.
  • Recombinant Human Factor VIII (rFVIII) Usage Expressed as Number of Infusions for Major Surgery - Part B [ Time Frame: Baseline up to 6 weeks during Part B ]
    Major surgery was defined as any surgical or invasive procedure (elective or emergent) in which the overall bleeding risk was excessive, required a general anesthetic in an individual without a bleeding disorder, penetrated or exposed a major body cavity, resulted in substantial impairment of physical or physiological functions, or required special anatomic knowledge or manipulative skill.
  • Recombinant Human Factor VIII (rFVIII) Usage Expressed as Total Dose per Kilogram per Infusion for Major Surgery - Part B [ Time Frame: Baseline up to 6 weeks during Part B ]
    Major surgery was defined as any surgical or invasive procedure (elective or emergent) in which the overall bleeding risk was excessive, required a general anesthetic in an individual without a bleeding disorder, penetrated or exposed a major body cavity, resulted in substantial impairment of physical or physiological functions, or required special anatomic knowledge or manipulative skill. Total dose per kilogram per Infusion was expressed in international units per kilogram per infusion (IU/kg/infusion).
  • Investigator's Assessment of Response to Treatment - Part B [ Time Frame: Baseline up to 6 weeks during Part B ]
    Subject's response to treatment was assessed by Investigator as excellent, good, moderate, poor or missing during Part B of the study. No subjects were assessed as poor.
  • Subject's Assessment of Response to Treatment of a Bleed - Part A [ Time Frame: Weeks 0 to 36 during Part A ]
    Adequacy of hemostasis was assessed by subject as excellent, good, moderate, poor or missing during Part A of the study.
  • Number of Subjects Developed Human Coagulation Factor VIII (FVIII) Inhibitor - Part A [ Time Frame: Weeks 0 to 36 during Part A ]
  • Change From Baseline in Overall Pain Severity and Interference due to Pain at Week 36 - Part A [ Time Frame: Week 0 (baseline) and Week 36 during Part A ]
    Brief Pain Inventor (BPI) - Short Form (BPI-SF) was a 15-item, self-administered, clinically valid, reliable and responsive measure developed to assess pain. BPI-SF was typically scored by averaging the pain severity score and overall pain interference score. Scores ranged from 0 to 10 and a higher score indicates a higher level of pain/interference. Mean change from baseline was reported in the below table. In the listed categories below, 'N' signifies the number of subjects evaluable for this outcome.
  • Change From Baseline in Work Productivity and Activity Impairment (WPAI) Questionnaire at Week 36 - Part A [ Time Frame: Week 0 (baseline) and Week 36 during Part A ]
    WPAI,a validated instrument to assess the effect of hemophilia on ability to work, attend classes, and perform regular daily activities in subjects aged 12 and above, also contained classroom impairment questions,which was self-administered and comprised of 9 questions that elicited info on work,classroom,and daily activity impairment during the previous 7 days.WPAI outcomes that are overall work and activity impairment, transformed to impairment percentages with higher numbers indicating greater impairment and less productivity. 'N' signifies the number of subjects evaluable for this outcome.
  • Change From Baseline in Quality of Life by Hemophilia Specific Quality of for Adults (Haemo-QoL-A) Overall Score at Week 36 - Part A [ Time Frame: Week 0 (baseline) and Week 36 during Part A ]
    Quality of life (QoL) was measured by the Haemo-QoL-A overall score, which ranged from 0 (the best condition) to 100 (the worst condition).
  • Maximum Drug Plasma Concentration (Cmax) Following Single and Multiple Doses of BAY94-9027 - Part A [ Time Frame: Weeks 0 and 36: pre-infusion (0 hours), post-infusion 15, 30 minutes, 1, 3, 6, 8, 24, 48, 72, 96 hours ]
    Maximum observed drug concentration, directly taken from analytical data. Geometric mean and percentage geometric coefficient of variation (%CV) were reported. Cmax was expressed in international Units per deciliter (IU/dL).
  • Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUC) Following Single and Multiple Doses of

    Original Secondary Outcome:

    • Safety variables will be summarized using descriptive statistics based on adverse events collection [ Time Frame: Baseline visit up to 32 weeks ]
    • Quantification of blood loss in major surgery [ Time Frame: Pre-surgery infusion up to 24 hours after surgery ]
    • Pharmacokinetic parameters will be measured by Tmax, Cmax, t1/2, AUC, and incremental recovery [ Time Frame: Baseline, 32 weeks ]


    Information By: Bayer

    Dates:
    Date Received: March 28, 2012
    Date Started: April 2012
    Date Completion: February 2017
    Last Updated: July 3, 2016
    Last Verified: July 2016