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

Primary Purpose

Hemophilia A With Inhibitors, Hemophilia B With Inhibitors

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Coagulation Factor VIIa (Recombinant)
Sponsored by
rEVO Biologics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hemophilia A With Inhibitors

Eligibility Criteria

12 Years - 75 Years (Child, Adult, Older Adult)MaleDoes not accept healthy volunteers

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).

Sites / Locations

  • Orthopaedic Hemophilia Treatment Center
  • University of California Davis Comprehensive Cancer Center
  • University of Colorado Hemophilia and Thrombosis Center
  • Rush University Medical Center
  • University of Minnesota Medical Center Fairview
  • Republican Research Center for Radiation Medicine and Human Ecology
  • Specialized Hospital for Active Treatment of Hematological Diseases
  • LTD HEMA
  • Chaim Sheba Medical Center, Tel-hashomer hospital
  • Institute of Hematology and Transfusion Medicine
  • Sandor SRL
  • Kirov Research Institute of Hematology and Blood Transfusion
  • Hematology Research Center
  • City Outpatient Clinic #37
  • Kyiv City Clinical Hospital #9
  • Institute of Blood Pathology and Transfusion Medicine of Academy of Medical Sciences of Ukraine
  • Basingstoke and North Hampshire Hospital, Hemophilia, Hemostasis and Thrombosis Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

FVIIa: 75 µg/kg first, then 225 µg/kg

FVIIa: 225 µg/kg first, then 75 µg/kg

Arm Description

Coagulation Factor VIIa (Recombinant): First Intervention (3 months), Second Intervention (3 months), repeat cycle until study completion.

Coagulation Factor VIIa (Recombinant): First Intervention (3 months), Second Intervention (3 months), repeat cycle until study completion.

Outcomes

Primary Outcome Measures

Proportion of Successfully Treated Mild/Moderate Bleeding Episodes
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
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
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
Total Amount of Study Drug Administered Per Mild/Moderate Bleeding Episode

Full Information

First Posted
December 18, 2013
Last Updated
May 15, 2017
Sponsor
rEVO Biologics
Collaborators
Laboratoire français de Fractionnement et de Biotechnologies
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1. Study Identification

Unique Protocol Identification Number
NCT02020369
Brief Title
Phase III Study of Coagulation FVIIa (Recombinant) in Congenital Hemophilia A or B Patients With Inhibitors
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
April 2014 (undefined)
Primary Completion Date
July 2015 (Actual)
Study Completion Date
August 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
rEVO Biologics
Collaborators
Laboratoire français de Fractionnement et de Biotechnologies

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemophilia A With Inhibitors, Hemophilia B With Inhibitors

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
27 (Actual)

8. Arms, Groups, and Interventions

Arm Title
FVIIa: 75 µg/kg first, then 225 µg/kg
Arm Type
Experimental
Arm Description
Coagulation Factor VIIa (Recombinant): First Intervention (3 months), Second Intervention (3 months), repeat cycle until study completion.
Arm Title
FVIIa: 225 µg/kg first, then 75 µg/kg
Arm Type
Experimental
Arm Description
Coagulation Factor VIIa (Recombinant): First Intervention (3 months), Second Intervention (3 months), repeat cycle until study completion.
Intervention Type
Biological
Intervention Name(s)
Coagulation Factor VIIa (Recombinant)
Intervention Description
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
Primary Outcome Measure Information:
Title
Proportion of Successfully Treated Mild/Moderate Bleeding Episodes
Description
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
Time Frame
12 hours after first administration of study drug
Secondary Outcome Measure Information:
Title
Proportion of Mild/Moderate Bleeding Episodes With Patient (Pt)-Reported "Good" or "Excellent" Responses at 12 Hours
Description
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 Frame
at 12 hours
Title
Time to Assessment of a "Good" or "Excellent" Response of Mild/Moderate Bleeding Episodes by the Patient
Description
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.
Time Frame
Within 24 hours of Bleeding Episode
Title
Number of Administrations of Study Drug Per Mild/Moderate Bleeding Episode
Time Frame
Within 24 hours of Bleeding Episode
Title
Total Amount of Study Drug Administered Per Mild/Moderate Bleeding Episode
Time Frame
Through study completion

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jean Francois Schved, MD
Organizational Affiliation
Saint Eloi Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Orthopaedic Hemophilia Treatment Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90007
Country
United States
Facility Name
University of California Davis Comprehensive Cancer Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
University of Colorado Hemophilia and Thrombosis Center
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
University of Minnesota Medical Center Fairview
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Republican Research Center for Radiation Medicine and Human Ecology
City
Gomel
Country
Belarus
Facility Name
Specialized Hospital for Active Treatment of Hematological Diseases
City
Sofia
Country
Bulgaria
Facility Name
LTD HEMA
City
Tbilisi
Country
Georgia
Facility Name
Chaim Sheba Medical Center, Tel-hashomer hospital
City
Ramat Gan
ZIP/Postal Code
5261
Country
Israel
Facility Name
Institute of Hematology and Transfusion Medicine
City
Warsaw
Country
Poland
Facility Name
Sandor SRL
City
Bucharest
Country
Romania
Facility Name
Kirov Research Institute of Hematology and Blood Transfusion
City
Kirov
Country
Russian Federation
Facility Name
Hematology Research Center
City
Moscow
Country
Russian Federation
Facility Name
City Outpatient Clinic #37
City
Saint-Petersburg
Country
Russian Federation
Facility Name
Kyiv City Clinical Hospital #9
City
Kyiv
Country
Ukraine
Facility Name
Institute of Blood Pathology and Transfusion Medicine of Academy of Medical Sciences of Ukraine
City
Lviv
Country
Ukraine
Facility Name
Basingstoke and North Hampshire Hospital, Hemophilia, Hemostasis and Thrombosis Center
City
Basingstoke
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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