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

NCT ID: NCT02020369

Last Updated: 2017-06-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-30
• Study Completion Date: 2015-08-31

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.

Conditions

Hemophilia A With Inhibitors; Hemophilia B With Inhibitors

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Coagulation Factor VIIa (Recombinant)

Intervention Type: BIOLOGICAL

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

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.

Group Type: EXPERIMENTAL

Coagulation Factor VIIa (Recombinant)

Intervention Type: BIOLOGICAL

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

Interventions

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

Intervention Type: BIOLOGICAL

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).

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Laboratoire français de Fractionnement et de Biotechnologies

INDUSTRY

Sponsor Role: collaborator

rEVO Biologics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jean Francois Schved, MD

Role: PRINCIPAL_INVESTIGATOR

Saint Eloi Hospital

Locations

Orthopaedic Hemophilia Treatment Center

Los Angeles, California, United States

University of California Davis Comprehensive Cancer Center

Sacramento, California, United States

University of Colorado Hemophilia and Thrombosis Center

Aurora, Colorado, United States

Rush University Medical Center

Chicago, Illinois, United States

University of Minnesota Medical Center Fairview

Minneapolis, Minnesota, United States

Republican Research Center for Radiation Medicine and Human Ecology

Homyel, , Belarus

Specialized Hospital for Active Treatment of Hematological Diseases

Sofia, , Bulgaria

LTD HEMA

Tbilisi, , Georgia

Chaim Sheba Medical Center, Tel-hashomer hospital

Ramat Gan, , Israel

Institute of Hematology and Transfusion Medicine

Warsaw, , Poland

Sandor SRL

Bucharest, , Romania

Kirov Research Institute of Hematology and Blood Transfusion

Kirov, , Russia

Hematology Research Center

Moscow, , Russia

City Outpatient Clinic #37

Saint Petersburg, , Russia

Kyiv City Clinical Hospital #9

Kyiv, , Ukraine

Institute of Blood Pathology and Transfusion Medicine of Academy of Medical Sciences of Ukraine

Lviv, , Ukraine

Basingstoke and North Hampshire Hospital, Hemophilia, Hemostasis and Thrombosis Center

Basingstoke, , United Kingdom

Countries

United States; Belarus; Bulgaria; Georgia; Israel; Poland; Romania; Russia; Ukraine; United Kingdom

References

Young G, Mahlangu J, Boggio LN, Carcao M, Dargaud Y, Escobar M, Giermasz A, Hermans C, Kuriakose P, Miesbach W, Nance D, Rafique A, Sidonio RF Jr, Vilchevska KV, Wang M, Pipe SW. Treatment of severe bleeds with eptacog beta in hemophilia A or B with inhibitors: a post hoc analysis of the PERSEPT 1 and 2 trials. Blood Vessel Thromb Hemost. 2025 Mar 27;2(3):100069. doi: 10.1016/j.bvth.2025.100069. eCollection 2025 Aug.

Reference Type: DERIVED

PMID: 40765904 (View on PubMed)

Carcao M, Hermans C, Giermasz A, Kessler C, Miesbach W, Quon D, Windyga J, Mahlangu J. Safety and Use of Eptacog Beta 225 microg/kg in Patients With Haemophilia A or B With Inhibitors. Haemophilia. 2025 Sep;31(5):957-965. doi: 10.1111/hae.70083. Epub 2025 Jul 17.

Reference Type: DERIVED

PMID: 40674256 (View on PubMed)

Other Identifiers

RB-FVIIa-006-13

Identifier Type: -

Identifier Source: org_study_id