A Phase I Safety, Pharmacokinetics and Pharmacodynamics Study of Recombinant Factor VIIa in Adult Patients With Hemophilia A or B (rhFVIIa)

• ClinicalTrials.gov Identifier: NCT01708564
• Recruitment Status: Completed
• First Posted: October 17, 2012
• Last Update Posted: July 30, 2013
• Sponsor: rEVO Biologics
• Information provided by (Responsible Party): rEVO Biologics

Study Description

Brief Summary:

This study will assess the pharmacokinetics and pharmacodynamics of rhFVIIa at three dose levels. The results will help identify the most optimal doses to take forward to the Phase 2/3 studies where bleedings in hemophilia patients with inhibitors will be treated with rhFVIIa.

Condition or disease	Intervention/treatment	Phase
Hemophilia	Biological: rhFVIIa	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 15 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: A Phase 1b, Dose Escalation Study to Assess the Safety, Pharmacokinetics and Pharmacodynamics of Coagulation Factor VIIa (Recombinant) in Congenital Hemophilia A or B Patients
• Study Start Date: October 2012
• Actual Primary Completion Date: June 2013
• Actual Study Completion Date: June 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cohort 1; 10 patients administered a single low dose of rhFVIIa	Biological: rhFVIIa; Patients will be administered low, intermediate and high doses of rhFVIIa; Other Name: Coagulation Factor VIIa (Recombinant)
Experimental: Cohort 2; 10 patients administered a single intermediate dose of rhFVIIa	Biological: rhFVIIa; Patients will be administered low, intermediate and high doses of rhFVIIa; Other Name: Coagulation Factor VIIa (Recombinant)
Experimental: Cohort 3; 10 patients administered a single high dose of rhFVIIa	Biological: rhFVIIa; Patients will be administered low, intermediate and high doses of rhFVIIa; Other Name: Coagulation Factor VIIa (Recombinant)

Outcome Measures

Primary Outcome Measures :

1. Factor VIIa concentration in patient plasma as measured by FVIIa PK and PD assays [ Time Frame: Up to 36 hours of dosing ]

Secondary Outcome Measures :

1. Incidence of patients with treatment emergent adverse events [ Time Frame: Up to 28 days after dosing ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. be male with a diagnosis of moderate or severe congenital hemophilia A and/or B (with or without inhibitors)
2. be 18 years or older, up to and including 75 years of age
3. be capable of understanding and willing to comply with the conditions of the protocol
4. have read, understood and provided written informed consent

Exclusion Criteria:

1. have any coagulation disorder other than hemophilia A or B
2. have a body weight >105 kg (231 lb)
3. be immuno-suppressed (i.e., the patient should not receive systemic immunosuppressive medication <30 days prior to enrollment, CD4 counts at screening should be >200/µl)
4. have a known allergy or hypersensitivity to rabbits
5. have platelet count <100,000/mL
6. have had within one month prior to first administration of the study drug in this study a major surgical procedure (e.g. orthopedic, abdominal)
7. have an active, ongoing bleeding for which the patient is being treated, or treatment for a bleeding was stopped within 24 hours of the time of study drug administration
8. have received a Factor VII or FVIIa containing product (either plasma derived or recombinant) within 72 hours prior to any study drug administration
9. 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
10. have a clinically relevant hepatic (hepatic enzymes >3 times the upper limit of normal) and/or renal impairment (creatinine >2 times the upper limit of normal)
11. 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, have an arterial stent in place or have clinically significant atherosclerotic disease (e.g., angina pectoris, peripheral vascular disease)
12. use any anticoagulant for arterial/venous obstructions and/or atrial fibrillation within 7 days prior to first study drug administration
13. have an active malignancy (those with non-melanoma skin cancer are allowed)
14. 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

Contacts and Locations

Locations

United States, California

UC Davis Health System Internal Medicine: Hematology & Oncology

Sacramento, California, United States, 95817

United States, Illinois

RUSH Hemophilia & Thrombophilia Center

Chicago, Illinois, United States, 60612

Netherlands

Centre for Human Drug Research

Leiden, Netherlands

Sponsors and Collaborators

rEVO Biologics

Investigators

• Study Director: Johan Frieling, MD,PhD; rEVO Biologics

More Information

• Responsible Party: rEVO Biologics
• ClinicalTrials.gov Identifier: NCT01708564
• Other Study ID Numbers: GTC-FVIIa-005-11; 2012-002285-13 ( EudraCT Number )
• First Posted: October 17, 2012
• Last Update Posted: July 30, 2013
• Last Verified: July 2013

Additional relevant MeSH terms:

Hemophilia A; Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn