Clinical trial NCT01440946: Study of Recombinant Coagulation Factor IX Fc Fusion Protein, BIIB029, in Previously Treated Pediatric Participants With Hemophilia B
Official title: An Open-label, Multicenter Evaluation of Safety, Pharmacokinetics and Efficacy of Recombinant Coagulation Factor IX Fc Fusion Protein, BIIB029, in the Prevention and Treatment of Bleeding Episodes in Pediatric Subjects With Hemophilia B
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hemophilia B
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Swedish Orphan Biovitrum
First posted: 2011-09-27
Enrollment: 30
Sex: MALE
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective of the study is to evaluate the safety of Recombinant Human Coagulation Factor IX Fc Fusion Protein (rFIXFc) in previously treated pediatric subjects with hemophilia B. Secondary objectives of this study in this study population are as follows: to evaluate the efficacy of rFIXFc for prevention and treatment of bleeding episodes; to evaluate and assess the pharmacokinetics (PK) of rFIXFc; to evaluate rFIXFc consumption for prevention and treatment of bleeding episodes

Detailed description: At the Baseline visit (28 ± 7 days prior to Day 1), participants receive a single IV injection of prestudy FIX over 10 (±5) minutes in the clinic under medical supervision at a dose of 50 IU/kg. A washout period with no FIX treatment is required prior to administration of prestudy FIX and prior to rFIXFc. A PK assessment is done with prestudy FIX and also done with rFIXFc on Day 1. After completing the PK assessments, participants begin weekly prophylactic treatment with rFIXFc for approximately 50 weeks, to obtain 50 EDs. One ED is defined as a 24-hour period in which a participant received 1 or more doses of rFIXFc, with the time of the first injection of rFIXFc defined as the start of the ED.

Eligibility criteria: Key Inclusion Criteria:

* Severe hemophilia B defined as ≤ 2 IU/dl (≤ 2%) endogenous FIX
* Male \< 12 years and weight ≥ 13 kg
* History of at least 50 documented prior exposure days to FIX
* No history of, or currently detectable, inhibitor

Key Exclusion Criteria:

* Other coagulation disorders in addition to Hemophilia B
* History of anaphylaxis associated with any FIX or IV immunoglobulin administration

NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.

Primary outcomes:
measure: Occurence of Factor IX (FIX) Inhibitor Development
timeFrame: Up to 50 weeks +/- 7 days, or up to 50 EDs if reached prior to Week 50
Secondary outcomes:
measure: Annualized Bleeding Rate
timeFrame: Up to 50 weeks +/- 7 days (efficacy period as defined in description)
measure: Annualized Joint Bleeding Rate (Spontaneous)
timeFrame: Up to 50 weeks +/- 7 days (efficacy period as defined in description)
measure: Participant Assessment of Response to Injections to Treat a Bleeding Episode
timeFrame: Up to 50 weeks +/- 7 days
measure: Physician's Global Assessment of the Participant's Response to His rFIXFc Regimen
timeFrame: Up to 50 weeks +/- 7 days
measure: Annualized rFIXFc Consumption by Type of Injection
timeFrame: Up to 50 weeks +/- 7 days (efficacy period as defined in description)
measure: Number of Days From the Last Prophylaxis Injection to a Spontaneous Bleeding Episode
timeFrame: Up to 50 weeks +/- 7 days (efficacy period as defined in description)
measure: Number of Injections Required for Resolution of a Bleeding Episode
timeFrame: Up to 50 weeks +/- 7 days (efficacy period as defined in description)
measure: Total Dose Required for Resolution of a Bleeding Episode
timeFrame: Up to 50 weeks +/- 7 days (efficacy period as defined in description)
measure: Maximum Plasma Activity (Cmax; One-stage Activated Partial Thromboplastin Time [aPTT] Clotting Assay)
timeFrame: Baseline (28±7 days before Day 1) Prestudy FIX Dosing: predose; 30±5 min, 3 hrs±30 min, 10±2 hrs, 24±3 hrs, 48±4 hrs postdose. Day 1 rFIXFc Dosing: predose; 30±5 min, 3 hrs ±30 min, 10±2 hrs, 24±3 hrs, 72±7 hrs, 120±12 hrs, 168±16 hrs postdose.
measure: Terminal Half Life (t1/2; One-stage aPTT Clotting Assay)
timeFrame: Baseline (28±7 days before Day 1) Prestudy FIX Dosing: predose; 30±5 min, 3 hrs±30 min, 10±2 hrs, 24±3 hrs, 48±4 hrs postdose. Day 1 rFIXFc Dosing: predose; 30±5 min, 3 hrs ±30 min, 10±2 hrs, 24±3 hrs, 72±7 hrs, 120±12 hrs, 168±16 hrs postdose.
measure: Clearance (CL; One-stage aPTT Clotting Assay)
timeFrame: Baseline (28±7 days before Day 1) Prestudy FIX Dosing: predose; 30±5 min, 3 hrs±30 min, 10±2 hrs, 24±3 hrs, 48±4 hrs postdose. Day 1 rFIXFc Dosing: predose; 30±5 min, 3 hrs ±30 min, 10±2 hrs, 24±3 hrs, 72±7 hrs, 120±12 hrs, 168±16 hrs postdose.
measure: Volume of Distribution at Steady State (Vss; One-stage aPTT Clotting Assay)
timeFrame: Baseline (28±7 days before Day 1) Prestudy FIX Dosing: predose; 30±5 min, 3 hrs±30 min, 10±2 hrs, 24±3 hrs, 48±4 hrs postdose. Day 1 rFIXFc Dosing: predose; 30±5 min, 3 hrs ±30 min, 10±2 hrs, 24±3 hrs, 72±7 hrs, 120±12 hrs, 168±16 hrs postdose.
measure: Dose Normalized Area Under the Curve (DNAUC; One-stage aPTT Clotting Assay)
timeFrame: Baseline (28±7 days before Day 1) Prestudy FIX Dosing: predose; 30±5 min, 3 hrs±30 min, 10±2 hrs, 24±3 hrs, 48±4 hrs postdose. Day 1 rFIXFc Dosing: predose; 30±5 min, 3 hrs ±30 min, 10±2 hrs, 24±3 hrs, 72±7 hrs, 120±12 hrs, 168±16 hrs postdose.
measure: Mean Residence Time (MRT; One-stage aPTT Clotting Assay)
timeFrame: Baseline (28±7 days before Day 1) Prestudy FIX Dosing: predose; 30±5 min, 3 hrs±30 min, 10±2 hrs, 24±3 hrs, 48±4 hrs postdose. Day 1 rFIXFc Dosing: predose; 30±5 min, 3 hrs ±30 min, 10±2 hrs, 24±3 hrs, 72±7 hrs, 120±12 hrs, 168±16 hrs postdose.
measure: Incremental Recovery (IR; One-stage aPTT Clotting Assay)
timeFrame: Baseline (28±7 days before Day 1) Prestudy FIX Dosing: predose; 30±5 min, 3 hrs±30 min, 10±2 hrs, 24±3 hrs, 48±4 hrs postdose. Day 1 rFIXFc Dosing: predose; 30±5 min, 3 hrs ±30 min, 10±2 hrs, 24±3 hrs, 72±7 hrs, 120±12 hrs, 168±16 hrs postdose.
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Sacramento
country: United States
facility: Research Site
state: California
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Honolulu
country: United States
facility: Research Site
state: Hawaii
city: Indianapolis
country: United States
facility: Research Site
state: Indiana
city: East Lansing
country: United States
facility: Research Site
state: Michigan
city: Pittsburgh
country: United States
facility: Research Site
state: Pennsylvania
city: Parkville
country: Australia
facility: Research Site
state: Victoria
city: Subiaco
country: Australia
facility: Research Site
state: Western Australia
city: Dublin
country: Ireland
facility: Research Site
city: Utrecht
country: Netherlands
facility: Research Site
city: Johannesburg
country: South Africa
facility: Research Site
city: Basingstoke
country: United Kingdom
facility: Research Site
city: Cambridge
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Bioverativ Therapeutics Inc.
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Fischer K, Kulkarni R, Nolan B, Mahlangu J, Rangarajan S, Gambino G, Diao L, Ramirez-Santiago A, Pierce GF, Allen G. Recombinant factor IX Fc fusion protein in children with haemophilia B (Kids B-LONG): results from a multicentre, non-randomised phase 3 study. Lancet Haematol. 2017 Feb;4(2):e75-e82. doi: 10.1016/S2352-3026(16)30193-4.