check_circleStudy Completed

Hemophilia A

Bayer Identifier:

13024

ClinicalTrials.gov Identifier:

NCT01580293

EudraCT Number:

2011-005210-11

EU CT Number:

Not Available
A trial investigating safety and efficacy of treatment with BAY94-9027 in severe Hemophilia A

Trial purpose

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.

Key Participants Requirements

Sex

Male

Age

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

Trial summary

Enrollment Goal
145
Trial Dates
April 2012 - November 2019
Phase
Phase 2/Phase 3
Could I Receive a placebo
No
Products
Jivi (Damoctocog, BAY94-9027)
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Withdrawn
Malmö, 205 02, Sweden
Completed
Wien, 1090, Austria
Completed
Wien, 1090, Austria
Completed
Ramat Gan, 5262000, Israel
Completed
Cleveland, 44106-6007, United States
Completed
Sheffield, S10 2JF, United Kingdom
Completed
London, SE1 7EH, United Kingdom
Completed
Newcastle Upon Tyne, NE1 4LP, United Kingdom
Completed
Oslo, 0372, Norway
Completed
Hershey, 17033, United States
Completed
Singapore, 169608, Singapore
Completed
Singapore, 119228, Singapore
Withdrawn
Corrientes, W3410AVV, Argentina
Completed
Singapore, 229 899, Singapore
Withdrawn
Kansas City, 64108-9898, United States
Withdrawn
Lexington, 40536, United States
Withdrawn
Pensacola, 32504, United States
Withdrawn
Bialystok, 15-276, Poland
Withdrawn
Warszawa, 02-776, Poland
Withdrawn
Wroclaw, 50-368, Poland
Completed
Wroclaw, 50-367, Poland
Withdrawn
Lublin, 20-081, Poland
Withdrawn
Stockholm, 171 76, Sweden
Completed
Columbus, 43205, United States
Withdrawn
Chattanooga, 37403, United States
Withdrawn
Atlanta, 30322, United States
Withdrawn
Philadelphia, 19104, United States
Completed
Jacksonville, 32207, United States
Completed
Miami, 33136, United States
Completed
MARSEILLE, 13005, France
Completed
RENNES CEDEX, 35033, France
Withdrawn
LEUVEN, 3000, Belgium
Completed
Brugge, 8000, Belgium
Completed
Groningen, 9713 GZ, Netherlands
Completed
AMSTERDAM, 1105 AZ, Netherlands
Withdrawn
EINDHOVEN, 5600 PD, Netherlands
Completed
Aarhus N, 8200, Denmark
Withdrawn
San Luis, D5702GOD, Argentina
Withdrawn
Córdoba, X5004CDT, Argentina
Withdrawn
Bahia Blanca, B8001HXM, Argentina
Completed
Bonn, 53127, Germany
Withdrawn
Mainz, 55131, Germany
Completed
Heidelberg, 69004, Germany
Withdrawn
Berlin, 10249, Germany
Withdrawn
Basingstoke, RG24 9NA, United Kingdom
Completed
Syracuse, 13210, United States
Completed
Detroit, 48202, United States
Completed
Seoul, 05278, Korea, Republic Of
Completed
Daejeon, 35233, Korea, Republic Of
Completed
Busan, 49241, Korea, Republic Of
Completed
Seoul, 03722, Korea, Republic Of
Completed
Richmond, 23298-0155, United States
Completed
Chicago, 60612, United States
Withdrawn
Edmonton, T6G 2E1, Canada
Completed
London, N6A 5W9, Canada
Withdrawn
Houston, 77030, United States
Withdrawn
Worcester, 01655, United States
Completed
Minneapolis, 55455, United States
Completed
Cincinnati, 45229-3039, United States
Withdrawn
San Antonio, 78207, United States
Withdrawn
Duarte, 91010, United States
Withdrawn
MONTPELLIER CEDEX, 34295, France
Completed
BRON cedex, 69677, France
Withdrawn
PARIS, 75015, France
Completed
REIMS CEDEX, 51092, France
Completed
Napoli, 80131, Italy
Completed
Milano, 20122, Italy
Completed
Roma, 00161, Italy
Withdrawn
Parma, 43126, Italy
Withdrawn
Napoli, 80144, Italy
Completed
Torino, 10126, Italy
Withdrawn
Ottawa, K1H 8L6, Canada
Completed
MAASTRICHT, 6229 HX, Netherlands
Completed
Izmir, 35100, Turkey
Completed
Ankara, 06100, Turkey
Completed
Baranquilla, 080020, Colombia
Completed
Medellin, 050030, Colombia
Completed
Taipei, 100, Taiwan
Completed
Taipei, 11217, Taiwan
Completed
Changhua, 50006, Taiwan
Withdrawn
Rochester, 14621, United States
Completed
Sacramento, 95817, United States
Completed
San Diego, 92103-8651, United States
Completed
DEN HAAG, 2545 CH, Netherlands
Completed
Hiroshima, 734-8551, Japan
Completed
Nishinomiya, 663-8501, Japan
Completed
Nagoya, 466-8560, Japan
Completed
Suginami, 167-0035, Japan
Completed
Shinjuku-ku, 160-0023, Japan
Completed
Kashihara, 634-8522, Japan
Completed
Tucson, 85724-5024, United States
Withdrawn
Little Rock, 72202, United States
Withdrawn
New Orleans, 70112, United States
Withdrawn
Medellin, 050034, Colombia
Completed
Timisoara, 300011, Romania
Withdrawn
Bucharest, 011026, Romania
Withdrawn
Bucharest, 022328, Romania
Withdrawn
Baia Mare, 430031, Romania

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
    Annualized number of total bleeds was defined as the annualized sum of spontaneous bleeds and trauma bleeds.
    date_rangeTime Frame:
    On-demand: Weeks 0 -36 and Prophylaxis: Weeks 10 - 36 during Part A
    enhanced_encryption
    Safety Issue:
    No

Secondary Outcome

  • Physician's Assessment of Adequacy of Hemostasis in Major Surgery –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.
    date_rangeTime Frame:
    Baseline up to 6 weeks during Part B
    enhanced_encryption
    Safety Issue:
    No
  • Recombinant Human Factor VIII (rFVIII) Usage Expressed as Number of Infusions for Major Surgery – 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.
    date_rangeTime Frame:
    Baseline up to 6 weeks during Part B
    enhanced_encryption
    Safety Issue:
    No
  • Recombinant Human Factor VIII (rFVIII) Usage Expressed as Total Dose per Kilogram per Infusion for Major Surgery – 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).
    date_rangeTime Frame:
    Baseline up to 6 weeks during Part B
    enhanced_encryption
    Safety Issue:
    No
  • Investigator’s Assessment of Response to Treatment - 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.
    date_rangeTime Frame:
    Baseline up to 6 weeks during Part B
    enhanced_encryption
    Safety Issue:
    No
  • Subject's Assessment of Response to Treatment of a Bleed – Part A
    Adequacy of hemostasis was assessed by subject as excellent, good, moderate, poor or missing during Part A of the study.
    date_rangeTime Frame:
    Weeks 0 to 36 during Part A
    enhanced_encryption
    Safety Issue:
    No
  • Number of Subjects Developed Human Coagulation Factor VIII (FVIII) Inhibitor – Part A
    date_rangeTime Frame:
    Weeks 0 to 36 during Part A
    enhanced_encryption
    Safety Issue:
    No
  • Change From Baseline in Overall Pain Severity and Interference due to Pain at Week 36 – 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.
    date_rangeTime Frame:
    Week 0 (baseline) and Week 36 during Part A
    enhanced_encryption
    Safety Issue:
    No
  • Change From Baseline in Work Productivity and Activity Impairment (WPAI) Questionnaire at Week 36 – 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.
    date_rangeTime Frame:
    Week 0 (baseline) and Week 36 during Part A
    enhanced_encryption
    Safety Issue:
    No
  • Change From Baseline in Quality of Life by Hemophilia Specific Quality of for Adults (Haemo-QoL-A) Overall Score at Week 36 – 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).
    date_rangeTime Frame:
    Week 0 (baseline) and Week 36 during Part A
    enhanced_encryption
    Safety Issue:
    No
  • Maximum Drug Plasma Concentration (Cmax) Following Single and Multiple Doses of BAY94-9027 – Part A
    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).
    date_rangeTime Frame:
    Weeks 0 and 36: pre-infusion (0 hours), post-infusion 15, 30 minutes, 1, 3, 6, 8, 24, 48, 72, 96 hours
    enhanced_encryption
    Safety Issue:
    No
  • Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUC) Following Single and Multiple Doses of BAY94-9027 – Part A
    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.
    date_rangeTime Frame:
    Weeks 0 and 36: pre-infusion (0 hours), post-infusion 15, 30 minutes, 1, 3, 6, 8, 24, 48, 72, 96 hours
    enhanced_encryption
    Safety Issue:
    No
  • Terminal Elimination Half Life (t1/2) Following Single and Multiple Doses of BAY94-9027 – Part A
    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.
    date_rangeTime Frame:
    Weeks 0 and 36: pre-infusion (0 hours), post-infusion 15, 30 minutes, 1, 3, 6, 8, 24, 48, 72, 96 hours
    enhanced_encryption
    Safety Issue:
    No
  • Overall Human Coagulation Factor VIII (FVIII) Recovery Value in Chromogenic Assay – Part A
    Recovery was calculated by the following formula: Recovery = (post-infusion FVIII activity – pre-infusion FVIII activity ) * weight / dose (in IU).
    date_rangeTime Frame:
    Weeks 0 to 36 during Part A
    enhanced_encryption
    Safety Issue:
    No
  • Bleed Location – Part A
    Bleed locations were categorised as joint, muscle, skin/mucosa, internal, others and missing.
    date_rangeTime Frame:
    Weeks 0 to 36 during Part A
    enhanced_encryption
    Safety Issue:
    No
  • Annualized Number of Joint Bleeds, Trauma, Spontaneous Bleeds for Subjects in Prophylaxis arm- Part A
    date_rangeTime Frame:
    Weeks 10 to 36
    enhanced_encryption
    Safety Issue:
    No
  • Recombinant Human Factor VIII (rFVIII) Usage Expressed as Number of Infusions– Part A
    date_rangeTime Frame:
    Weeks 0 to 36
    enhanced_encryption
    Safety Issue:
    No
  • Recombinant Human Factor VIII (rFVIII) Usage Expressed as Total Dose per Kilogram per Year – Part A
    date_rangeTime Frame:
    Weeks 0 to 36
    enhanced_encryption
    Safety Issue:
    No
  • Recombinant Human Factor VIII (rFVIII) Usage Expressed as Total Dose per Kilogram per Infusion - Part A
    date_rangeTime Frame:
    Weeks 0 to 36 during Part A
    enhanced_encryption
    Safety Issue:
    No
  • Recombinant Human Factor VIII(rFVIII) Usage Expressed as Total Dose per Kilogram In Subjects with Prophylaxis Treatment – Part A
    date_rangeTime Frame:
    Weeks 0 to 36 during Part A
    enhanced_encryption
    Safety Issue:
    No
  • Number of Infusions to Control the Bleed – Part A
    date_rangeTime Frame:
    Weeks 0 to 36
    enhanced_encryption
    Safety Issue:
    No
  • Number of Bleeds Over Time Since Previous Prophylaxis Infusion - Part A
    date_rangeTime Frame:
    Weeks 0 to 36
    enhanced_encryption
    Safety Issue:
    No
  • Number of Subjects Requiring Dose Escalation or Dose Increase During Weeks 10 to 36 – Part A
    date_rangeTime Frame:
    Weeks 10 to 36 during Part A
    enhanced_encryption
    Safety Issue:
    No
  • Physician's Assessment of Adequacy of Hemostasis During Minor Surgery – Part A
    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.
    date_rangeTime Frame:
    Weeks 0 to 36 during Part A
    enhanced_encryption
    Safety Issue:
    No
  • Safety variables will be summarized using descriptive statistics based on adverse events collection
    date_rangeTime Frame:
    Baseline visit up until end of treatment
    enhanced_encryption
    Safety Issue:
    Yes

Trial design

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
Trial Type
Interventional
Intervention Type
Biological/Vaccine
Trial Purpose
Treatment
Allocation
Randomized
Blinding
Open Label
Assignment
Parallel Assignment
Trial Arms
4

Additional Information

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