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

NCT02020369 | Completed Phase 3 Results DMC

• 1 other identifier: RB-FVIIa-006-13
• Study Type: interventional
• Target: 27
• Locations: 10 countries
• Sites: 17

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

Conditions

Hemophilia A With Inhibitors; Hemophilia B With Inhibitors

Outcome Measures

Primary Outcomes (1)

• 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

  12 hours after first administration of study drug

Secondary Outcomes (4)

• Proportion of Mild/Moderate Bleeding Episodes With Patient (Pt)-Reported "Good" or "Excellent" Responses at 12 Hours

  at 12 hours

• Time to Assessment of a "Good" or "Excellent" Response of Mild/Moderate Bleeding Episodes by the Patient

  Within 24 hours of Bleeding Episode

• Number of Administrations of Study Drug Per Mild/Moderate Bleeding Episode

  Within 24 hours of Bleeding Episode

• Total Amount of Study Drug Administered Per Mild/Moderate Bleeding Episode

  Through study completion

Study Arms (2)

FVIIa: 75 µg/kg first, then 225 µg/kg

EXPERIMENTAL

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

Biological: Coagulation Factor VIIa (Recombinant)

FVIIa: 225 µg/kg first, then 75 µg/kg

EXPERIMENTAL

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

Biological: Coagulation Factor VIIa (Recombinant)

Interventions

Coagulation Factor VIIa (Recombinant) 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; FVIIa: 75 µg/kg first, then 225 µg/kg

Eligibility Criteria

• Age: 12 Years - 75 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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).

Sponsors & Collaborators

• rEVO Biologics: lead
• Laboratoire français de Fractionnement et de Biotechnologies: collaborator

Study Sites (17)

Orthopaedic Hemophilia Treatment Center

Los Angeles, California, 90007, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

University of Colorado Hemophilia and Thrombosis Center

Aurora, Colorado, 80045, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Minnesota Medical Center Fairview

Minneapolis, Minnesota, 55455, United States

Location

Republican Research Center for Radiation Medicine and Human Ecology

Homyel, Belarus

Location

Specialized Hospital for Active Treatment of Hematological Diseases

Sofia, Bulgaria

Location

LTD HEMA

Tbilisi, Georgia

Location

Chaim Sheba Medical Center, Tel-hashomer hospital

Ramat Gan, 5261, Israel

Location

Institute of Hematology and Transfusion Medicine

Warsaw, Poland

Location

Sandor SRL

Bucharest, Romania

Location

Kirov Research Institute of Hematology and Blood Transfusion

Kirov, Russia

Location

Hematology Research Center

Moscow, Russia

Location

City Outpatient Clinic #37

Saint Petersburg, Russia

Location

Kyiv City Clinical Hospital #9

Kyiv, Ukraine

Location

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

Lviv, Ukraine

Location

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

Basingstoke, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 40765904 DERIVED

• 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.

  PMID: 40674256 DERIVED

MeSH Terms

Interventions

Factor VII

Intervention Hierarchy (Ancestors)

Enzyme Precursors; Enzymes and Coenzymes; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Protein Precursors; Biological Factors

Results Point of Contact

• Title: Jeffry Lawrence, MD, Vice President, Clinical Development
• Organization: LFB USA Inc.

jeffry.lawrence@lfb-usa.com

+1.508.370.5113

Study Officials

• Jean Francois Schved, MD

  Saint Eloi Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2013
• First Posted: December 24, 2013
• Study Start: April 1, 2014
• Primary Completion: July 1, 2015
• Study Completion: August 1, 2015
• Last Updated: June 14, 2017
• Results First Posted: June 14, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (5); UA (2); RO (1); GE (1); BE (1); BU (1); IL (1); RU (3); GB (1); PL (1)