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

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

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.

Study Overview

• Status: Completed
• Conditions: Hemophilia
• Intervention / Treatment: Biological: rhFVIIa

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Leiden, Netherlands
    • Centre For Human Drug Research
• United States
  • California
    • Sacramento, California, United States, 95817
      • UC Davis Health System Internal Medicine: Hematology & Oncology
  • Illinois
    • Chicago, Illinois, United States, 60612
      • RUSH Hemophilia & Thrombophilia Center

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / 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 Names: 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 Names: 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 Names: Coagulation Factor VIIa (Recombinant)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Factor VIIa concentration in patient plasma as measured by FVIIa PK and PD assays	Up to 36 hours of dosing

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of patients with treatment emergent adverse events	Up to 28 days after dosing

Collaborators and Investigators

• Sponsor: rEVO Biologics
• Investigators: Study Director: Johan Frieling, MD,PhD, rEVO Biologics

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: October 15, 2012
• First Submitted That Met QC Criteria: October 15, 2012
• First Posted (Estimate): October 17, 2012

Study Record Updates

• Last Update Posted (Estimate): July 30, 2013
• Last Update Submitted That Met QC Criteria: July 29, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Hemophilia A
• Other Study ID Numbers: GTC-FVIIa-005-11; 2012-002285-13 (EudraCT Number)