Clinical trial NCT01027364: Study of Recombinant Factor IX Fc Fusion Protein (rFIXFc) in Participants With Hemophilia B
Official title: B-LONG: An Open-Label, Multicenter Evaluation of the Safety, Pharmacokinetics, and Efficacy of Recombinant, Long-acting Coagulation Factor IX Fc Fusion Protein (rFIXFc) in the Prevention and Treatment of Bleeding in Previously Treated Subjects With Severe Hemophilia B
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Severe Hemophilia B
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Swedish Orphan Biovitrum
First posted: 2009-12-07
Enrollment: 123
Sex: MALE
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objectives of the study were: to evaluate the safety and tolerability of rFIXFc; to evaluate the efficacy of rFIXFc in all treatment arms; to evaluate the effectiveness of prophylaxis over on-demand (episodic) therapy by comparing the annualized number of bleeding episodes between participants receiving rFIXFc on each prevention (prophylaxis) regimen and participants receiving rFIXFc on an episodic regimen. The secondary objectives of the study were: to evaluate and assess the pharmacokinetic (PK) parameter estimates of rFIXFc and rFIX (BeneFIX®) at baseline in the Sequential PK subgroup as well as rFIXFc at Week 26 (±1 week); to evaluate participants' response to treatment; to evaluate rFIXFc consumption.


Eligibility criteria: Inclusion Criteria:

* Male and 12 years of age and older and weigh at least 40 kg
* Diagnosed with hemophilia B (baseline Factor IX level less than or equal to 2%)
* History of at least 100 exposure days to any Factor IX product
* Platelet count ≥100,000 cells/μL

Exclusion Criteria:

* History of Factor IX inhibitors
* Kidney or liver dysfunction
* Diagnosed with another coagulation defect other than hemophilia B
* Prior history of anaphylaxis associated with any Factor IX or intravenous (IV) immunoglobulin administration

Primary outcomes:
measure: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities
timeFrame: up to 52 weeks ± 1 week
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
timeFrame: up to 52 weeks + 30 days ± 1 week
measure: Number of Participants With Non-serious Treatment-emergent Adverse Events (TEAEs) During the Surgical / Rehabilitation Period
timeFrame: up to 52 weeks + 30 days ± 1 week
measure: Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) During the Surgical / Rehabilitation Period
timeFrame: up to 52 weeks + 30 days ± 1 week
measure: Incidence Rate of FIX Inhibitor Development
timeFrame: up to 52 weeks ± 1 week
measure: Annualized Bleeding Rate
timeFrame: up to 52 weeks ± 1 week (efficacy period as defined in description)
measure: Comparison of Annualized Bleeding Rates
timeFrame: up to 52 weeks ± 1 week (efficacy period as defined in description)
Secondary outcomes:
measure: Participant Assessment of Response to Injections to Treat a Bleeding Episode
timeFrame: up to 52 weeks ± 1 week
measure: Physicians' Global Assessments of Participants' Response to Treatment With rFIXFc
timeFrame: up to 52 weeks ± 1 week
measure: Annualized rFIXFc Consumption Per Participant
timeFrame: up to 52 weeks ± 1 week (efficacy period as defined in description)
measure: Average Weekly Dose For the Fixed Weekly Interval Prophylaxis Arm
timeFrame: up to 52 weeks ± 1 week (efficacy period as defined in description)
measure: Average Dosing Interval For the Individualized Interval Prophylaxis Arm
timeFrame: up to 52 weeks ± 1 week (efficacy period as defined in description)
measure: Annualized Bleeding Rate by Type of Bleed (Spontaneous and Traumatic)
timeFrame: up to 52 weeks ± 1 week (efficacy period as defined in description)
measure: Annualized Bleeding Rate by Location of Bleed (Joint, Muscle, Internal, Skin/Mucosa)
timeFrame: up to 52 weeks ± 1 week (efficacy period as defined in description)
measure: Number of Days From Last Injection to Treat a New Bleeding Episode
timeFrame: up to 52 weeks ± 1 week (efficacy period as defined in description)
measure: Number of Injections Required for Resolution of a Bleeding Episode
timeFrame: up to 52 weeks ± 1 week (efficacy period as defined in description)
measure: Number of Injections Required for Resolution of a Bleeding Episode by Location of Bleed
timeFrame: up to 52 weeks ± 1 week (efficacy period as defined in description)
measure: Total Dose Per Injection Required for Resolution of a Bleeding Episode by Location of Bleed
timeFrame: up to 52 weeks ± 1 week (efficacy period as defined in description)
measure: Hemophilia-Specific Quality of Life Index for Adults (Haem-A-QoL) Questionnaire: Change From Baseline to Week 26
timeFrame: Baseline, Week 26
measure: Haem-A-QoL Questionnaire for Adults: Change From Baseline to Week 52
timeFrame: Baseline, Week 52
measure: Hemophilia-Specific Quality of Life Index for Children (Haemo-QoL) Questionnaire: Change From Baseline to Week 26 and Week 52
timeFrame: Baseline, Week 26, Week 52
measure: Investigators'/Surgeons' Assessment of Participants' Response to rFIXFc for Major Surgery
timeFrame: up to 52 weeks ± 1 week
measure: Number of Injections Required to Maintain Hemostasis During Major Surgery
timeFrame: up to 52 weeks ± 1 week
measure: Dose Per Injection and Total Dose Required to Maintain Hemostasis During Major Surgery
timeFrame: up to 52 weeks ± 1 week
measure: Estimated Total Blood Loss During Major Surgery
timeFrame: up to 52 weeks ± 1 week
measure: Number of Transfusions Required Per Surgery
timeFrame: up to 52 weeks ± 1 week
measure: Maximum Concentration (Cmax)
timeFrame: See Measure Description for complete time frame. Each participant was to complete PK sampling up to, and including, the 96-hour (4-day) timepoint for BeneFIX PK assessment and the 240-hour (10-day) timepoint for rFIXFc PK assessment.
measure: Area Under the Curve (AUC) Per Dose
timeFrame: See Measure Description for complete time frame. Each participant was to complete PK sampling up to, and including, the 96-hour (4-day) timepoint for BeneFIX PK assessment and the 240-hour (10-day) timepoint for rFIXFc PK assessment.
measure: Half Life (t1/2) Alpha and t1/2 Beta
timeFrame: See Measure Description for complete time frame. Each participant was to complete PK sampling up to, and including, the 96-hour (4-day) timepoint for BeneFIX PK assessment and the 240-hour (10-day) timepoint for rFIXFc PK assessment.
measure: Clearance (CL)
timeFrame: See Measure Description for complete time frame. Each participant was to complete PK sampling up to, and including, the 96-hour (4-day) timepoint for BeneFIX PK assessment and the 240-hour (10-day) timepoint for rFIXFc PK assessment.
measure: Mean Residence Time (MRT)
timeFrame: See Measure Description for complete time frame. Each participant was to complete PK sampling up to, and including, the 96-hour (4-day) timepoint for BeneFIX PK assessment and the 240-hour (10-day) timepoint for rFIXFc PK assessment.
measure: Volume in Steady State (Vss)
timeFrame: See Measure Description for complete time frame. Each participant was to complete PK sampling up to, and including, the 96-hour (4-day) timepoint for BeneFIX PK assessment and the 240-hour (10-day) timepoint for rFIXFc PK assessment.
measure: Incremental Recovery
timeFrame: See Measure Description for complete time frame. Each participant was to complete PK sampling up to, and including, the 96-hour (4-day) timepoint for BeneFIX PK assessment and the 240-hour (10-day) timepoint for rFIXFc PK assessment.
measure: Time to 1% and 3% FIX Activity
timeFrame: See Measure Description for complete time frame. Each participant was to complete PK sampling up to, and including, the 96-hour (4-day) timepoint for BeneFIX PK assessment and the 240-hour (10-day) timepoint for rFIXFc PK assessment.
measure: Number of Participants With Clinically Relevant Abnormalities or Relevant Changes From Baseline in Vital Signs
timeFrame: up to 52 weeks ± 1 week
measure: Coagulation Parameter: Change From Pre-dose Values in Prothrombin Split Fragments 1+ 2 (F 1+2)
timeFrame: Pre-dose, 1 hour post-dose, 6 hours post-dose, and 24 hours post-dose at baseline (120 hours before Day 1, for BeneFIX), Day 1, Week 26, and Week 52 (for rFIXFc)
measure: Coagulation Parameter: Change From Pre-dose Values in Thrombin-antithrombin (TAT) Complex
timeFrame: Pre-dose, 1 hour post-dose, 6 hours post-dose, and 24 hours post-dose at baseline (120 hours before Day 1, for BeneFIX), Day 1, Week 26, and Week 52 (for rFIXFc)
measure: Coagulation Parameter: Change From Pre-dose Values in D-dimer
timeFrame: Pre-dose, 1 hour post-dose, 6 hours post-dose, and 24 hours post-dose at baseline (120 hours before Day 1, for BeneFIX), Day 1, Week 26, and Week 52 (for rFIXFc)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Sacramento
country: United States
facility: Research Site
state: California
city: Aurora
country: United States
facility: Research Site
state: Colorado
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Indianapolis
country: United States
facility: Research Site
state: Indiana
city: East Lansing
country: United States
facility: Research Site
state: Michigan
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Research Site
state: Pennsylvania
city: Seattle
country: United States
facility: Research Site
state: Washington
city: Camperdown
country: Australia
facility: Research Site
state: New South Wales
city: Adelaide
country: Australia
facility: Research Site
state: South Australia
city: Perth
country: Australia
facility: Research Site
state: Western Australia
city: Bruxelles
country: Belgium
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Campinas
country: Brazil
facility: Research Site
city: Calgary
country: Canada
facility: Research Site
state: Alberta
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Vancouver
country: Canada
facility: Research Site
city: Beijing
country: China
facility: Research site
city: Guangzhou
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Tianjin
country: China
facility: Research Site
city: Lyon
country: France
facility: Research Site
city: Marseille
country: France
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Bonn
country: Germany
facility: Research Site
city: Pokfulam
country: Hong Kong
facility: Research Site
city: Shatin
country: Hong Kong
facility: Research Site
city: Ludhiana
country: India
facility: Research Site
state: Punjab
city: Vellore
country: India
facility: Research Site
state: Tamil Nadu
city: Bangalore
country: India
facility: Research Site
city: Pune
country: India
facility: Research Site
city: Firenze
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Kasihara-City
country: Japan
facility: Research Site
city: Kawasaki City
country: Japan
facility: Research Site
city: Kitakyushu
country: Japan
facility: Research Site
city: Nagoya
country: Japan
facility: Research Site
city: Suginami-ku
country: Japan
facility: Ressearch Site
city: Tokyo
country: Japan
facility: Research Site
city: Lodz
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: St. Petersburg
country: Russian Federation
facility: Research Site
city: Johannesburg
country: South Africa
facility: Research Site
state: Gauteng
city: Cape Town
country: South Africa
facility: Research Site
state: Western Cape
city: Malmö
country: Sweden
facility: Research Site
city: Stockholm
country: Sweden
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: Powell JS, Pasi KJ, Ragni MV, Ozelo MC, Valentino LA, Mahlangu JN, Josephson NC, Perry D, Manco-Johnson MJ, Apte S, Baker RI, Chan GC, Novitzky N, Wong RS, Krassova S, Allen G, Jiang H, Innes A, Li S, Cristiano LM, Goyal J, Sommer JM, Dumont JA, Nugent K, Vigliani G, Brennan A, Luk A, Pierce GF; B-LONG Investigators. Phase 3 study of recombinant factor IX Fc fusion protein in hemophilia B. N Engl J Med. 2013 Dec 12;369(24):2313-23. doi: 10.1056/NEJMoa1305074. Epub 2013 Dec 4.