Phase I/IIa Study of FIXFc in Hemophilia B Patients

A Phase I/IIa Safety and Pharmacokinetic Study of Intravenous FIXFc in Previously Treated Hemophilia B Patients

The primary objective of the study is to assess safety of FIXFc at doses ranging from 1 to 100 IU/kg.

Study Overview

• Status: Completed
• Conditions: Hemophilia B
• Intervention / Treatment: Drug: rFIXFc

Detailed Description

This study was previously posted by Syntonix Pharmaceuticals, Inc. In January, 2007, sponsorship of the trial was transferred to Biogen Idec. In February, 2017, sponsorship of the trial was transferred to Bioverativ.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Indiana Hemophilia & Thrombosis center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham & Women's Hospital
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina Medical School
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Hemophilia Center of Western PA
  • Washington
    • Seattle, Washington, United States, 98104
      • Puget Sound Blood Center

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

1. Are previously treated (PTPs) with severe (<2 IU/dL endogenous FIX level) hemophilia B and at least 150 prior documented exposure days to other FIX products.
2. Have no prior history of or currently detectable inhibitor defined as > 0.6 Bethesda units by the local lab. A family history of inhibitors will not exclude the patient.
3. No prior history of an allergic reaction or anaphylaxis associated with any FIX or IVIG administration.
4. No concurrent autoimmune disease.
5. At least 7 days since their last dose of FIX (wash-out period).
6. Certain laboratory testing criteria and other protocol-defined criteria may apply.
7. HIV negative or if HIV positive with a CD4 count ≥ 200 cells/mm3. HIV patients are allowed to receive protease inhibitors per the discretion of the Investigator.

Key Exclusion Criteria:

1. Presence of a major bleeding episode on Day 1 of study.
2. Any coagulation disorder in addition to hemophilia B.
3. A patient currently on a dose and regimen of FIX that would preclude participation in the study due to possible increased risk of bleeding because of the requirement to withhold treatment during the study period.
4. A positive d-dimer at screening.
5. Documented history of liver cirrhosis.
6. Positive for HBsAg and/or positive for hepatitis C antibody, and/or HIV positive with an ALT or AST greater than 5 times upper limit of normal.
7. Certain prior illnesses and other protocol-defined criteria.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: rFIXFc; Six intravenous (IV) dose levels, 1, 5, 12.5, 25, 50, and 100 IU/kg	Drug: rFIXFc; As specified in the treatment arm; Other Names: Alprolix; BIIB029; recombinant factor IX fusion protein; FIXFc

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants experiencing Adverse Events	Up to 45 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to reach maximum concentration (Tmax)	Up to 45 days
Maximum concentration (Cmax)	Up to 45 days
Half-life (t½)	Up to 45 days
Clearance (CL)	Up to 45 days
Volume of distribution (Vd)	Up to 45 days
Area under the curve (AUC)	Up to 45 days
Mean residence time (MRT)	Up to 45 days
Incremental recovery (K)	Up to 45 days
Factor IX protein (FIX) activity	Up to 45 days
Recombinant (FIXFc) concentration over time curves	up to 45 days

Collaborators and Investigators

• Sponsor: Bioverativ Therapeutics Inc.
• Collaborators: Swedish Orphan Biovitrum; Syntonix Pharmaceuticals, Inc.
• Investigators: Study Director: Medical Director, Bioverativ Therapeutics Inc.

Publications and helpful links

General Publications

• Shapiro AD, Ragni MV, Valentino LA, Key NS, Josephson NC, Powell JS, Cheng G, Thompson AR, Goyal J, Tubridy KL, Peters RT, Dumont JA, Euwart D, Li L, Hallen B, Gozzi P, Bitonti AJ, Jiang H, Luk A, Pierce GF. Recombinant factor IX-Fc fusion protein (rFIXFc) demonstrates safety and prolonged activity in a phase 1/2a study in hemophilia B patients. Blood. 2012 Jan 19;119(3):666-72. doi: 10.1182/blood-2011-07-367003. Epub 2011 Nov 22.

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Actual): October 1, 2009
• Study Completion (Actual): October 1, 2009

Study Registration Dates

• First Submitted: July 14, 2008
• First Submitted That Met QC Criteria: July 14, 2008
• First Posted (Estimate): July 16, 2008

Study Record Updates

• Last Update Posted (Actual): December 19, 2020
• Last Update Submitted That Met QC Criteria: December 16, 2020
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Hemophilia B severe, previously treated patients
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Blood Coagulation Disorders; Hemophilia A; Hemophilia B
• Other Study ID Numbers: SYN-FIXFc-07-001