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Phase III Study of Coagulation FVIIa (Recombinant) in Congenital Hemophilia A or B Patients With Inhibitors

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02020369
First Posted: December 24, 2013
Last Update Posted: June 14, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Laboratoire français de Fractionnement et de Biotechnologies
Information provided by (Responsible Party):
rEVO Biologics
  Purpose
The purpose of the study is to assess the safety, efficacy and pharmacokinetics of 2 separate dose regimens (75µg/kg and 225 µg/kg) of Coagulation Factor VIIa (Recombinant) for the treatment of bleeding episodes in hemophilia A or B patients with inhibitors to Factor VIII/IX

Condition Intervention Phase
Hemophilia A With Inhibitors Hemophilia B With Inhibitors Biological: Coagulation Factor VIIa (Recombinant) Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase III Study on the Safety, Pharmacokinetics and Efficacy of Coagulation Factor VIIa (Recombinant) in Congenital Hemophilia A or B Patients With Inhibitors to Factor VIII or IX

Resource links provided by NLM:


Further study details as provided by rEVO Biologics:

Primary Outcome Measures:
  • Proportion of Successfully Treated Mild/Moderate Bleeding Episodes [ Time Frame: 12 hours after first administration of study drug ]

    For the primary efficacy endpoint, successful treatment of a bleeding episode was defined as a combination of the following:

    • "Good" or "Excellent" response noted by the patient
    • Study drug treatment: No further treatment with study drug beyond timepoint for this bleeding episode
    • No other hemostatic treatment needed for this bleeding episode
    • No administration of blood products that would indicate continuation of bleeding beyond timepoint
    • No increase of pain beyond timepoint that could not otherwise be explained


Secondary Outcome Measures:
  • Proportion of Mild/Moderate Bleeding Episodes With Patient (Pt)-Reported "Good" or "Excellent" Responses at 12 Hours [ Time Frame: at 12 hours ]

    Based on Patient-Reported "Good" or "Excellent" responses as per the below descriptions:

    Good: Symptoms of bleed (e.g., swelling, tenderness, and decreased range of motion in the case of musculoskeletal haemorrhage) had largely been reduced by the treatment, but had not completely disappeared. Symptoms had improved enough to not require more infusions of the study drug.

    Excellent: Full relief of pain and cessation of objective signs of bleed (e.g., swelling, tenderness, and decreased range of motion in the case of musculoskeletal haemorrhage). No additional infusion of study drug was required.


  • Time to Assessment of a "Good" or "Excellent" Response of Mild/Moderate Bleeding Episodes by the Patient [ Time Frame: Within 24 hours of Bleeding Episode ]

    Categories of Response to Treatment are Described as Follows:

    None: No noticeable effect of the treatment on the bleed or worsening of patient's condition. Continuation of treatment with the study drug was needed.

    Moderate: Some effect of the treatment on the bleed was noticed, e.g., pain decreased or bleeding signs improved, but bleed continued and required continued treatment with the study drug. Good: Symptoms of bleed (e.g., swelling, tenderness, and decreased range of motion in the case of musculoskeletal haemorrhage) had largely been reduced by the treatment, but had not completely disappeared. Symptoms had improved enough to not require more infusions of the study drug.

    Excellent: Full relief of pain and cessation of objective signs of bleed (e.g., swelling, tenderness, and decreased range of motion in the case of musculoskeletal haemorrhage). No additional infusion of study drug was required.


  • Number of Administrations of Study Drug Per Mild/Moderate Bleeding Episode [ Time Frame: Within 24 hours of Bleeding Episode ]
  • Total Amount of Study Drug Administered Per Mild/Moderate Bleeding Episode [ Time Frame: Through study completion ]

Enrollment: 27
Study Start Date: April 2014
Study Completion Date: August 2015
Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: FVIIa: 75 µg/kg first, then 225 µg/kg
Coagulation Factor VIIa (Recombinant): First Intervention (3 months), Second Intervention (3 months), repeat cycle until study completion.
Biological: Coagulation Factor VIIa (Recombinant)
A cross over design to assess the efficacy of 2 separate dose regimens (75µg/kg and 225 µg/kg) of Coagulation Factor VIIa (Recombinant) for the treatment of bleeding episodes in hemophilia A or B patients with inhibitors to Factor VIII/IX
Experimental: FVIIa: 225 µg/kg first, then 75 µg/kg
Coagulation Factor VIIa (Recombinant): First Intervention (3 months), Second Intervention (3 months), repeat cycle until study completion.
Biological: Coagulation Factor VIIa (Recombinant)
A cross over design to assess the efficacy of 2 separate dose regimens (75µg/kg and 225 µg/kg) of Coagulation Factor VIIa (Recombinant) for the treatment of bleeding episodes in hemophilia A or B patients with inhibitors to Factor VIII/IX

Detailed Description:

This was a global, multicenter, Phase III, prospective, open-label, randomized, crossover study. After obtaining informed consent and performance of screening procedures, patients who met all inclusion and exclusion criteria were randomized to one of two treatment regimens as follows:

  • 75 µg/kg treatment regimen
  • 225 µg/kg treatment regimen

For each treatment regimen there were two phases:

  • Phase A (Initial phase)
  • Phase B (Treatment phase)

The assigned treatment regimen was the dose administered in Phase A and was the starting dose in Phase B.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   12 Years to 75 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • be male with a diagnosis of congenital hemophilia A and/or B of any severity
  • have one of the following:
  • a positive inhibitor test Bethesda Unit (BU) ≥ 5 (as confirmed at screening by the institutional lab), OR
  • a BU<5 but expected to have a high anamnestic response to FVIII or FIX, as demonstrated from the subject's medical history, precluding the use of Factor VIII or IX products to treat bleedings, OR
  • a BU<5 but expected to be refractory to increased dosing of FVIII or FIX, as demonstrated from the subject's medical history, precluding the use of Factor VIII or IX products to treat bleedings
  • be 12 years or older, up to and including 75 years of age (NOTE: different age restrictions may apply per local regulation and/or ethical considerations)
  • have at least 3 bleeding episodes of any severity in the past 6 months be capable of understanding and willing to comply with the conditions of the protocol
  • have read, understood and provided written informed consent (patient and/or parent(s)/legal guardian(s) if <18 years of age)

Exclusion Criteria:

  • have any coagulation disorder other than hemophilia A or B
  • be immuno-suppressed (i.e., the patient should not be receiving systemic immunosuppressive medication, cluster of differentiation 4 (CD4) counts at screening should be >200/µl)
  • have a known allergy or hypersensitivity to rabbits
  • have platelet count <100,000/mL
  • have had within one month prior to first administration of the study drug in this study a major surgical procedure (e.g. orthopedic, abdominal)
  • have received an investigational drug within 30 days of the first study drug administration, or is expected to receive such drug during participation in this study
  • have a clinically relevant hepatic (AST and/or alanine aminotransferase (ALT) >3 times the upper limit of normal) and/or renal impairment (creatinine >2 times the upper limit of normal)
  • have a history of arterial and/or venous thromboembolic events (such as myocardial infarction, ischemic strokes, transient ischemic attacks, deep venous thrombosis or pulmonary embolism) within 2 years prior to first dose of study drug, or current New York Heart Association (NYHA) functional classification score of stage II -IV
  • have an active malignancy (those with non-melanoma skin cancer are allowed)
  • have any life-threatening disease or other disease or condition which, according to the investigator's judgment, could imply a potential hazard to the patient, interfere with the trial participation or trial outcome (e.g., a history of non-responsiveness to bypassing products).
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02020369


Locations
United States, California
Orthopaedic Hemophilia Treatment Center
Los Angeles, California, United States, 90007
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States, 95817
United States, Colorado
University of Colorado Hemophilia and Thrombosis Center
Aurora, Colorado, United States, 80045
United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612
United States, Minnesota
University of Minnesota Medical Center Fairview
Minneapolis, Minnesota, United States, 55455
Belarus
Republican Research Center for Radiation Medicine and Human Ecology
Gomel, Belarus
Bulgaria
Specialized Hospital for Active Treatment of Hematological Diseases
Sofia, Bulgaria
Georgia
LTD HEMA
Tbilisi, Georgia
Israel
Chaim Sheba Medical Center, Tel-hashomer hospital
Ramat Gan, Israel, 5261
Poland
Institute of Hematology and Transfusion Medicine
Warsaw, Poland
Romania
Sandor SRL
Bucharest, Romania
Russian Federation
Kirov Research Institute of Hematology and Blood Transfusion
Kirov, Russian Federation
Hematology Research Center
Moscow, Russian Federation
City Outpatient Clinic #37
Saint-Petersburg, Russian Federation
Ukraine
Kyiv City Clinical Hospital #9
Kyiv, Ukraine
Institute of Blood Pathology and Transfusion Medicine of Academy of Medical Sciences of Ukraine
Lviv, Ukraine
United Kingdom
Basingstoke and North Hampshire Hospital, Hemophilia, Hemostasis and Thrombosis Center
Basingstoke, United Kingdom
Sponsors and Collaborators
rEVO Biologics
Laboratoire français de Fractionnement et de Biotechnologies
Investigators
Principal Investigator: Jean Francois Schved, MD Saint Eloi Hospital
  More Information

Responsible Party: rEVO Biologics
ClinicalTrials.gov Identifier: NCT02020369     History of Changes
Other Study ID Numbers: RB-FVIIa-006-13
First Submitted: December 18, 2013
First Posted: December 24, 2013
Results First Submitted: July 12, 2016
Results First Posted: June 14, 2017
Last Update Posted: June 14, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Hemophilia A
Hemophilia B
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Factor VIII
Coagulants