A Trial Investigating Safety and Efficacy of Treatment With BAY94-9027 in Severe Hemophilia A (PROTECT-VIII)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT01580293
First received: March 28, 2012
Last updated: July 3, 2016
Last verified: July 2016

March 28, 2012
July 3, 2016
April 2012
June 2014   (final data collection date for primary outcome measure)
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 ] [ Designated as safety issue: No ]
Annualized number of total bleeds was defined as the annualized sum of spontaneous bleeds and trauma bleeds.
Annualized number of total bleeds [ Time Frame: In the period of 32 weeks after Baseline ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01580293 on ClinicalTrials.gov Archive Site
  • Physician's Assessment of Adequacy of Hemostasis in Major Surgery -Part B [ Time Frame: Baseline up to 6 weeks during Part B ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 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 ] [ Designated as safety issue: No ]
    AUC=AUC(0-tlast)+Clast,calc/lambdaZ.AUC(0-tlast) is defined as AUC from time 0 to the last data point >lower limit of quantitation (LLOQ),calculated up by linear trapezoidal rule, down by logarithmic trapezoidal rule.Clast is the last concentration value above LLOQ,directly taken from analytical data.lambdaZ is the apparent terminal rate constant,calculated from the slope of a log-linear regression of the unweighted data considering the last concentration time points>LLOQ (3 IU/dL).AUC expressed in hour*IU/dL.Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
  • Terminal Elimination Half Life (t1/2) 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 ] [ Designated as safety issue: No ]
    t1/2=ln2/ lambdaZ. lambdaZ is the apparent terminal rate constant, calculated from the slope of a loglinear regression of the unweighted data considering the last concentration time points >LLOQ (3 IU/dL). Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
  • Overall Human Coagulation Factor VIII (FVIII) Recovery Value in Chromogenic Assay - Part A [ Time Frame: Weeks 0 to 36 during Part A ] [ Designated as safety issue: No ]
    Recovery was calculated by the following formula: Recovery = (post-infusion FVIII activity - pre-infusion FVIII activity ) * weight / dose (in IU).
  • Bleed Location - Part A [ Time Frame: Weeks 0 to 36 during Part A ] [ Designated as safety issue: No ]
    Bleed locations were categorised as joint, muscle, skin/mucosa, internal, others and missing.
  • Annualized Number of Joint Bleeds, Trauma, Spontaneous Bleeds for Subjects in Prophylaxis arm- Part A [ Time Frame: Weeks 10 to 36 ] [ Designated as safety issue: No ]
  • Recombinant Human Factor VIII (rFVIII) Usage Expressed as Number of Infusions- Part A [ Time Frame: Weeks 0 to 36 ] [ Designated as safety issue: No ]
  • Recombinant Human Factor VIII (rFVIII) Usage Expressed as Total Dose per Kilogram per Year - Part A [ Time Frame: Weeks 0 to 36 ] [ Designated as safety issue: No ]
  • Recombinant Human Factor VIII (rFVIII) Usage Expressed as Total Dose per Kilogram per Infusion - Part A [ Time Frame: Weeks 0 to 36 during Part A ] [ Designated as safety issue: No ]
  • Recombinant Human Factor VIII(rFVIII) Usage Expressed as Total Dose per Kilogram In Subjects with Prophylaxis Treatment - Part A [ Time Frame: Weeks 0 to 36 during Part A ] [ Designated as safety issue: No ]
  • Number of Infusions to Control the Bleed - Part A [ Time Frame: Weeks 0 to 36 ] [ Designated as safety issue: No ]
  • Number of Bleeds Over Time Since Previous Prophylaxis Infusion - Part A [ Time Frame: Weeks 0 to 36 ] [ Designated as safety issue: No ]
  • Number of Subjects Requiring Dose Escalation or Dose Increase During Weeks 10 to 36 - Part A [ Time Frame: Weeks 10 to 36 during Part A ] [ Designated as safety issue: No ]
  • Physician's Assessment of Adequacy of Hemostasis During Minor Surgery - Part A [ Time Frame: Weeks 0 to 36 during Part A ] [ Designated as safety issue: No ]
    Minor surgery was defined as any surgical procedure that did not meet the definition of major, and included simple dental extractions, incision and drainage of abscesses, or simple excisions. A total of 17 minor surgeries performed in 10 subjects were reported during Part A of the study. Adequacy of hemostasis was assessed as excellent or good by the Physician during Part A of the study. The maximum blood loss during surgery was 100 mL during the draining of an abscess. No subjects required blood transfusions.
  • Safety variables will be summarized using descriptive statistics based on adverse events collection [ Time Frame: Baseline visit up until end of treatment ] [ Designated as safety issue: Yes ]
  • Safety variables will be summarized using descriptive statistics based on adverse events collection [ Time Frame: Baseline visit up to 32 weeks ] [ Designated as safety issue: Yes ]
  • Quantification of blood loss in major surgery [ Time Frame: Pre-surgery infusion up to 24 hours after surgery ] [ Designated as safety issue: No ]
  • Pharmacokinetic parameters will be measured by Tmax, Cmax, t1/2, AUC, and incremental recovery [ Time Frame: Baseline, 32 weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Trial Investigating Safety and Efficacy of Treatment With BAY94-9027 in Severe Hemophilia A
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 A

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.

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.

Interventional
Phase 2
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Hemophilia A
Biological: BAY94-9027
Intravenous infusion of BAY94-9027
  • Experimental: Arm 1
    On-demand treatment of BAY94-9027 at individual dose and number of infusions based upon location and severity of bleeds
    Intervention: Biological: BAY94-9027
  • Experimental: Arm 2
    Prophylaxis treatment of BAY94-9027; 2 infusions per week over 10 weeks followed by 2 infusions per week over 26 weeks in the main trial; and at least 1 day per week in the extension for at least 100 ED
    Intervention: Biological: BAY94-9027
  • Experimental: Arm 3
    Prophylaxis treatment of BAY94-9027; 2 infusions per week over 10 weeks followed by infusion every 5 days over 26 weeks in the main trial; and at least 1 day per week in the extension for at least 100 ED
    Intervention: Biological: BAY94-9027
  • Experimental: Arm 4
    Prophylaxis treatment of BAY94-9027; 2 infusions per week over 10 weeks followed by infusion every 7 days over 26 weeks in the main trial; and at least 1 day per week in the extension for at least 100 ED
    Intervention: Biological: BAY94-9027
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
141
February 2017
June 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Male; 12-65 years of age
  • Subjects with severe hemophilia A
  • Previously treated with factor VIII for a minimum of 150 exposure days

Exclusion Criteria:

  • Inhibitors to FVIII (current evidence or history)
  • Any other inherited or acquired bleeding disorder in addition to Hemophilia A
  • Platelet count < 100,000/mm3
  • Creatinine > 2x upper limit of normal or AST/ALT (aspartate aminotransferase/alanine aminotransferase) > 5x upper limit of normal
Male
12 Years to 65 Years   (Child, Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Argentina,   Austria,   Belgium,   Canada,   Colombia,   Denmark,   France,   Germany,   Israel,   Italy,   Japan,   Korea, Republic of,   Netherlands,   Norway,   Poland,   Romania,   Singapore,   Sweden,   Taiwan,   Turkey,   United Kingdom
 
NCT01580293
13024, 2011-005210-11
Yes
Not Provided
Not Provided
Bayer
Bayer
Not Provided
Study Director: Bayer Study Director Bayer
Bayer
July 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP