Trial Condition(s):
Hemophilia A
A trial investigating safety and efficacy of treatment with BAY94-9027 in severe Hemophilia A (PROTECT-VIII)
Bayer Identifier:
13024
ClinicalTrials.gov Identifier:
EudraCT Number:
EU CT Number:
Not Available
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.
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
Trial Summary
Enrollment Goal
Trial Dates
Phase
Could I receive a placebo?
Products
Accepts Healthy Volunteers
Where to Participate
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Locations Investigative Site Wien, Austria, 1090 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Ramat Gan, Israel, 5262000 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Cleveland, United States, 44106-6007 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Sheffield, United Kingdom, S10 2JF | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site London, United Kingdom, SE1 7EH | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Newcastle Upon Tyne, United Kingdom, NE1 4LP | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Oslo, Norway, 0372 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Hershey, United States, 17033 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Singapore, Singapore, 169608 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Singapore, Singapore, 119228 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Singapore, Singapore, 229 899 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Wroclaw, Poland, 50-367 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Columbus, United States, 43205 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Jacksonville, United States, 32207 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Miami, United States, 33136 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site MARSEILLE, France, 13005 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site RENNES CEDEX, France, 35033 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Brugge, Belgium, 8000 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Groningen, Netherlands, 9713 GZ | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site AMSTERDAM, Netherlands, 1105 AZ | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Aarhus N, Denmark, 8200 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Bonn, Germany, 53127 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Heidelberg, Germany, 69004 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Syracuse, United States, 13210 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Detroit, United States, 48202 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Seoul, South Korea, 05278 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Daejeon, South Korea, 35233 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Busan, South Korea, 49241 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Seoul, South Korea, 03722 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Richmond, United States, 23298-0155 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Chicago, United States, 60612 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site London, Canada, N6A 5W9 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Minneapolis, United States, 55455 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Cincinnati, United States, 45229-3039 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site BRON cedex, France, 69677 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site REIMS CEDEX, France, 51092 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Napoli, Italy, 80131 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Milano, Italy, 20122 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Roma, Italy, 00161 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Torino, Italy, 10126 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site MAASTRICHT, Netherlands, 6229 HX | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Izmir, Turkey, 35100 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Ankara, Turkey, 06100 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Baranquilla, Colombia, 080020 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Medellin, Colombia, 050030 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Taipei, Taiwan, China, 100 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Taipei, Taiwan, China, 11217 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Changhua, Taiwan, China, 50006 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Sacramento, United States, 95817 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site San Diego, United States, 92103-8651 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site DEN HAAG, Netherlands, 2545 CH | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Hiroshima, Japan, 734-8551 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Nishinomiya, Japan, 663-8501 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Nagoya, Japan, 466-8560 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Suginami, Japan, 167-0035 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Shinjuku-ku, Japan, 160-0023 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Kashihara, Japan, 634-8522 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Tucson, United States, 85724-5024 | Contact Us: E-mail: [email protected] Phone: Not Available |
Locations Investigative Site Timisoara, Romania, 300011 | Contact Us: E-mail: [email protected] Phone: Not Available |
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
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 AAnnualized number of total bleeds was defined as the annualized sum of spontaneous bleeds and trauma bleeds.Timeframe: On-demand: Weeks 0 -36 and Prophylaxis: Weeks 10 - 36 during Part A
Secondary Outcome
- Physician's Assessment of Adequacy of Hemostasis in Major Surgery –Part BMajor 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.Timeframe: Baseline up to 6 weeks during Part B
- Recombinant Human Factor VIII (rFVIII) Usage Expressed as Number of Infusions for Major Surgery – Part BMajor 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.Timeframe: Baseline up to 6 weeks during Part B
- Recombinant Human Factor VIII (rFVIII) Usage Expressed as Total Dose per Kilogram per Infusion for Major Surgery – Part BMajor 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).Timeframe: Baseline up to 6 weeks during Part B
- Investigator’s Assessment of Response to Treatment - Part BSubject'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.Timeframe: Baseline up to 6 weeks during Part B
- Subject's Assessment of Response to Treatment of a Bleed – Part AAdequacy of hemostasis was assessed by subject as excellent, good, moderate, poor or missing during Part A of the study.Timeframe: Weeks 0 to 36 during Part A
- Number of Subjects Developed Human Coagulation Factor VIII (FVIII) Inhibitor – Part ATimeframe: Weeks 0 to 36 during Part A
- Change From Baseline in Overall Pain Severity and Interference due to Pain at Week 36 – Part ABrief 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.Timeframe: Week 0 (baseline) and Week 36 during Part A
- Change From Baseline in Work Productivity and Activity Impairment (WPAI) Questionnaire at Week 36 – Part AWPAI,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.Timeframe: Week 0 (baseline) and Week 36 during Part A
- Change From Baseline in Quality of Life by Hemophilia Specific Quality of for Adults (Haemo-QoL-A) Overall Score at Week 36 – Part AQuality of life (QoL) was measured by the Haemo-QoL-A overall score, which ranged from 0 (the best condition) to 100 (the worst condition).Timeframe: Week 0 (baseline) and Week 36 during Part A
- Maximum Drug Plasma Concentration (Cmax) Following Single and Multiple Doses of BAY94-9027 – Part AMaximum 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).Timeframe: Weeks 0 and 36: pre-infusion (0 hours), post-infusion 15, 30 minutes, 1, 3, 6, 8, 24, 48, 72, 96 hours
- Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUC) Following Single and Multiple Doses of BAY94-9027 – Part AAUC=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.Timeframe: Weeks 0 and 36: pre-infusion (0 hours), post-infusion 15, 30 minutes, 1, 3, 6, 8, 24, 48, 72, 96 hours
- Terminal Elimination Half Life (t1/2) Following Single and Multiple Doses of BAY94-9027 – Part At1/2=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.Timeframe: Weeks 0 and 36: pre-infusion (0 hours), post-infusion 15, 30 minutes, 1, 3, 6, 8, 24, 48, 72, 96 hours
- Overall Human Coagulation Factor VIII (FVIII) Recovery Value in Chromogenic Assay – Part ARecovery was calculated by the following formula: Recovery = (post-infusion FVIII activity – pre-infusion FVIII activity ) * weight / dose (in IU).Timeframe: Weeks 0 to 36 during Part A
- Bleed Location – Part ABleed locations were categorised as joint, muscle, skin/mucosa, internal, others and missing.Timeframe: Weeks 0 to 36 during Part A
- Annualized Number of Joint Bleeds, Trauma, Spontaneous Bleeds for Subjects in Prophylaxis arm- Part ATimeframe: Weeks 10 to 36
- Recombinant Human Factor VIII (rFVIII) Usage Expressed as Number of Infusions– Part ATimeframe: Weeks 0 to 36
- Recombinant Human Factor VIII (rFVIII) Usage Expressed as Total Dose per Kilogram per Year – Part ATimeframe: Weeks 0 to 36
- Recombinant Human Factor VIII (rFVIII) Usage Expressed as Total Dose per Kilogram per Infusion - Part ATimeframe: Weeks 0 to 36 during Part A
- Recombinant Human Factor VIII(rFVIII) Usage Expressed as Total Dose per Kilogram In Subjects with Prophylaxis Treatment – Part ATimeframe: Weeks 0 to 36 during Part A
- Number of Infusions to Control the Bleed – Part ATimeframe: Weeks 0 to 36
- Number of Bleeds Over Time Since Previous Prophylaxis Infusion - Part ATimeframe: Weeks 0 to 36
- Number of Subjects Requiring Dose Escalation or Dose Increase During Weeks 10 to 36 – Part ATimeframe: Weeks 10 to 36 during Part A
- Physician's Assessment of Adequacy of Hemostasis During Minor Surgery – Part AMinor 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.Timeframe: Weeks 0 to 36 during Part A
- Safety variables will be summarized using descriptive statistics based on adverse events collectionTimeframe: Baseline visit up until end of treatment
Additional Information
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