Clinical trial NCT00716716: Phase I/IIa Study of FIXFc in Hemophilia B Patients
Official title: A Phase I/IIa Safety and Pharmacokinetic Study of Intravenous FIXFc in Previously Treated Hemophilia B Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hemophilia B
Keywords: Hemophilia B severe, previously treated patients
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Syntonix Pharmaceuticals, Inc.
name: Swedish Orphan Biovitrum
First posted: 2008-07-16
Enrollment: 10
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants experiencing Adverse Events
timeFrame: Up to 45 days
Secondary outcomes:
measure: Time to reach maximum concentration (Tmax)
timeFrame: Up to 45 days
measure: Maximum concentration (Cmax)
timeFrame: Up to 45 days
measure: Half-life (t½)
timeFrame: Up to 45 days
measure: Clearance (CL)
timeFrame: Up to 45 days
measure: Volume of distribution (Vd)
timeFrame: Up to 45 days
measure: Area under the curve (AUC)
timeFrame: Up to 45 days
measure: Mean residence time (MRT)
timeFrame: Up to 45 days
measure: Incremental recovery (K)
timeFrame: Up to 45 days
measure: Factor IX protein (FIX) activity
timeFrame: Up to 45 days
measure: Recombinant (FIXFc) concentration over time curves
timeFrame: up to 45 days
Other outcomes:
Locations:
city: Chicago
country: United States
facility: RUSH University Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Hemophilia & Thrombosis Center
state: Indiana
city: Boston
country: United States
facility: Brigham & Women's Hospital
state: Massachusetts
city: Chapel Hill
country: United States
facility: University of North Carolina Medical School
state: North Carolina
city: Pittsburgh
country: United States
facility: Hemophilia Center of Western PA
state: Pennsylvania
city: Seattle
country: United States
facility: Puget Sound Blood Center
state: Washington
Study officials:
affiliation: Bioverativ Therapeutics Inc.
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.