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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01027364




Registration number
NCT01027364
Ethics application status
Date submitted
4/12/2009
Date registered
7/12/2009
Date last updated
19/12/2020

Titles & IDs
Public title
Study of Recombinant Factor IX Fc Fusion Protein (rFIXFc) in Participants With Hemophilia B
Scientific 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
Secondary ID [1] 0 0
2009-014295-21
Secondary ID [2] 0 0
998HB102
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Severe Hemophilia B 0 0
Condition category
Condition code
Blood 0 0 0 0
Clotting disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental: Fixed Weekly Interval - 50 IU/kg rFIXFc via intravenous (IV) injection once every 7 days initially, then at a dose indicated by the participant's baseline pharmacokinetic (PK) assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial weekly dose of rFIXFc (50 IU/kg) were to be made based on baseline PK assessments, occurrence of spontaneous bleeding episodes, and the trough levels, which were to be monitored at Weeks 4, 16, 26, and 39.

Prior to the first dose of rFIXFc, participants in the Sequential PK subgroup were to receive a single dose of 50 IU/kg BeneFIX administered IV in the clinic, followed by PK sampling. A single dose of 50 IU/kg rFIXFc was administered following a 120-hour washout from BeneFIX, followed by PK sampling for a baseline PK profiling. At Week 26 (±1 week) subjects were to receive a single dose of 50 IU/kg rFIXFc for repeat PK profiling.

Experimental: Individualized Interval - 100 IU/kg rFIXFc via IV injection once every 10 days initially, then at an interval derived from the baseline PK assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial 10-day interval were to be made based on baseline PK assessments and trough levels, which were monitored at Weeks 4, 16, 26, and 39.

Experimental: On Demand - 20 to 100 IU/kg rFIXFc via IV injection, or the dose indicated by the participant's baseline PK to target a plasma level of 20% to 100%, as needed for the treatment of mild to severe bleeding episodes

Experimental: Surgery - The surgical period and dosing are dependent on the type of surgery the participant undergoes. Participants who started the study in one of the other treatment arms prior to surgery will return to the original treatment arm. Participants who joined the study in the Surgery arm will be assigned to one of the other treatment arms following post-operative rehabilitation.
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities
Timepoint [1] 0 0
up to 52 weeks ± 1 week
Primary outcome [2] 0 0
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Timepoint [2] 0 0
up to 52 weeks + 30 days ± 1 week
Primary outcome [3] 0 0
Number of Participants With Non-serious Treatment-emergent Adverse Events (TEAEs) During the Surgical / Rehabilitation Period
Timepoint [3] 0 0
up to 52 weeks + 30 days ± 1 week
Primary outcome [4] 0 0
Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) During the Surgical / Rehabilitation Period
Timepoint [4] 0 0
up to 52 weeks + 30 days ± 1 week
Primary outcome [5] 0 0
Incidence Rate of FIX Inhibitor Development
Timepoint [5] 0 0
up to 52 weeks ± 1 week
Primary outcome [6] 0 0
Annualized Bleeding Rate
Timepoint [6] 0 0
up to 52 weeks ± 1 week (efficacy period as defined in description)
Primary outcome [7] 0 0
Comparison of Annualized Bleeding Rates
Timepoint [7] 0 0
up to 52 weeks ± 1 week (efficacy period as defined in description)
Secondary outcome [1] 0 0
Participant Assessment of Response to Injections to Treat a Bleeding Episode
Timepoint [1] 0 0
up to 52 weeks ± 1 week
Secondary outcome [2] 0 0
Physicians' Global Assessments of Participants' Response to Treatment With rFIXFc
Timepoint [2] 0 0
up to 52 weeks ± 1 week
Secondary outcome [3] 0 0
Annualized rFIXFc Consumption Per Participant
Timepoint [3] 0 0
up to 52 weeks ± 1 week (efficacy period as defined in description)
Secondary outcome [4] 0 0
Average Weekly Dose For the Fixed Weekly Interval Prophylaxis Arm
Timepoint [4] 0 0
up to 52 weeks ± 1 week (efficacy period as defined in description)
Secondary outcome [5] 0 0
Average Dosing Interval For the Individualized Interval Prophylaxis Arm
Timepoint [5] 0 0
up to 52 weeks ± 1 week (efficacy period as defined in description)
Secondary outcome [6] 0 0
Annualized Bleeding Rate by Type of Bleed (Spontaneous and Traumatic)
Timepoint [6] 0 0
up to 52 weeks ± 1 week (efficacy period as defined in description)
Secondary outcome [7] 0 0
Annualized Bleeding Rate by Location of Bleed (Joint, Muscle, Internal, Skin/Mucosa)
Timepoint [7] 0 0
up to 52 weeks ± 1 week (efficacy period as defined in description)
Secondary outcome [8] 0 0
Number of Days From Last Injection to Treat a New Bleeding Episode
Timepoint [8] 0 0
up to 52 weeks ± 1 week (efficacy period as defined in description)
Secondary outcome [9] 0 0
Number of Injections Required for Resolution of a Bleeding Episode
Timepoint [9] 0 0
up to 52 weeks ± 1 week (efficacy period as defined in description)
Secondary outcome [10] 0 0
Number of Injections Required for Resolution of a Bleeding Episode by Location of Bleed
Timepoint [10] 0 0
up to 52 weeks ± 1 week (efficacy period as defined in description)
Secondary outcome [11] 0 0
Total Dose Per Injection Required for Resolution of a Bleeding Episode by Location of Bleed
Timepoint [11] 0 0
up to 52 weeks ± 1 week (efficacy period as defined in description)
Secondary outcome [12] 0 0
Hemophilia-Specific Quality of Life Index for Adults (Haem-A-QoL) Questionnaire: Change From Baseline to Week 26
Timepoint [12] 0 0
Baseline, Week 26
Secondary outcome [13] 0 0
Haem-A-QoL Questionnaire for Adults: Change From Baseline to Week 52
Timepoint [13] 0 0
Baseline, Week 52
Secondary outcome [14] 0 0
Hemophilia-Specific Quality of Life Index for Children (Haemo-QoL) Questionnaire: Change From Baseline to Week 26 and Week 52
Timepoint [14] 0 0
Baseline, Week 26, Week 52
Secondary outcome [15] 0 0
Investigators'/Surgeons' Assessment of Participants' Response to rFIXFc for Major Surgery
Timepoint [15] 0 0
up to 52 weeks ± 1 week
Secondary outcome [16] 0 0
Number of Injections Required to Maintain Hemostasis During Major Surgery
Timepoint [16] 0 0
up to 52 weeks ± 1 week
Secondary outcome [17] 0 0
Dose Per Injection and Total Dose Required to Maintain Hemostasis During Major Surgery
Timepoint [17] 0 0
up to 52 weeks ± 1 week
Secondary outcome [18] 0 0
Estimated Total Blood Loss During Major Surgery
Timepoint [18] 0 0
up to 52 weeks ± 1 week
Secondary outcome [19] 0 0
Number of Transfusions Required Per Surgery
Timepoint [19] 0 0
up to 52 weeks ± 1 week
Secondary outcome [20] 0 0
Maximum Concentration (Cmax)
Timepoint [20] 0 0
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.
Secondary outcome [21] 0 0
Area Under the Curve (AUC) Per Dose
Timepoint [21] 0 0
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.
Secondary outcome [22] 0 0
Half Life (t1/2) Alpha and t1/2 Beta
Timepoint [22] 0 0
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.
Secondary outcome [23] 0 0
Clearance (CL)
Timepoint [23] 0 0
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.
Secondary outcome [24] 0 0
Mean Residence Time (MRT)
Timepoint [24] 0 0
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.
Secondary outcome [25] 0 0
Volume in Steady State (Vss)
Timepoint [25] 0 0
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.
Secondary outcome [26] 0 0
Incremental Recovery
Timepoint [26] 0 0
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.
Secondary outcome [27] 0 0
Time to 1% and 3% FIX Activity
Timepoint [27] 0 0
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.
Secondary outcome [28] 0 0
Number of Participants With Clinically Relevant Abnormalities or Relevant Changes From Baseline in Vital Signs
Timepoint [28] 0 0
up to 52 weeks ± 1 week
Secondary outcome [29] 0 0
Coagulation Parameter: Change From Pre-dose Values in Prothrombin Split Fragments 1+ 2 (F 1+2)
Timepoint [29] 0 0
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)
Secondary outcome [30] 0 0
Coagulation Parameter: Change From Pre-dose Values in Thrombin-antithrombin (TAT) Complex
Timepoint [30] 0 0
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)
Secondary outcome [31] 0 0
Coagulation Parameter: Change From Pre-dose Values in D-dimer
Timepoint [31] 0 0
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)

Eligibility
Key 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
Minimum age
12 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/12/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/07/2012
Sample size
Target
Accrual to date
Final
123
Recruitment in Australia
Recruitment state(s)
NSW,SA,WA
Recruitment hospital [1] 0 0
Research Site - Camperdown
Recruitment hospital [2] 0 0
Research Site - Adelaide
Recruitment hospital [3] 0 0
Research Site - Perth
Recruitment postcode(s) [1] 0 0
- Camperdown
Recruitment postcode(s) [2] 0 0
- Adelaide
Recruitment postcode(s) [3] 0 0
- Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Indiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
Washington
Country [9] 0 0
Belgium
State/province [9] 0 0
Bruxelles
Country [10] 0 0
Belgium
State/province [10] 0 0
Leuven
Country [11] 0 0
Brazil
State/province [11] 0 0
Campinas
Country [12] 0 0
Canada
State/province [12] 0 0
Alberta
Country [13] 0 0
Canada
State/province [13] 0 0
Ontario
Country [14] 0 0
Canada
State/province [14] 0 0
Quebec
Country [15] 0 0
Canada
State/province [15] 0 0
Vancouver
Country [16] 0 0
China
State/province [16] 0 0
Beijing
Country [17] 0 0
China
State/province [17] 0 0
Guangzhou
Country [18] 0 0
China
State/province [18] 0 0
Shanghai
Country [19] 0 0
China
State/province [19] 0 0
Tianjin
Country [20] 0 0
France
State/province [20] 0 0
Lyon
Country [21] 0 0
France
State/province [21] 0 0
Marseille
Country [22] 0 0
Germany
State/province [22] 0 0
Berlin
Country [23] 0 0
Germany
State/province [23] 0 0
Bonn
Country [24] 0 0
Hong Kong
State/province [24] 0 0
Pokfulam
Country [25] 0 0
Hong Kong
State/province [25] 0 0
Shatin
Country [26] 0 0
India
State/province [26] 0 0
Punjab
Country [27] 0 0
India
State/province [27] 0 0
Tamil Nadu
Country [28] 0 0
India
State/province [28] 0 0
Bangalore
Country [29] 0 0
India
State/province [29] 0 0
Pune
Country [30] 0 0
Italy
State/province [30] 0 0
Firenze
Country [31] 0 0
Italy
State/province [31] 0 0
Milano
Country [32] 0 0
Japan
State/province [32] 0 0
Kasihara-City
Country [33] 0 0
Japan
State/province [33] 0 0
Kawasaki City
Country [34] 0 0
Japan
State/province [34] 0 0
Kitakyushu
Country [35] 0 0
Japan
State/province [35] 0 0
Nagoya
Country [36] 0 0
Japan
State/province [36] 0 0
Suginami-ku
Country [37] 0 0
Japan
State/province [37] 0 0
Tokyo
Country [38] 0 0
Poland
State/province [38] 0 0
Lodz
Country [39] 0 0
Poland
State/province [39] 0 0
Warszawa
Country [40] 0 0
Russian Federation
State/province [40] 0 0
Moscow
Country [41] 0 0
Russian Federation
State/province [41] 0 0
St. Petersburg
Country [42] 0 0
South Africa
State/province [42] 0 0
Gauteng
Country [43] 0 0
South Africa
State/province [43] 0 0
Western Cape
Country [44] 0 0
Sweden
State/province [44] 0 0
Malmö
Country [45] 0 0
Sweden
State/province [45] 0 0
Stockholm
Country [46] 0 0
United Kingdom
State/province [46] 0 0
Cambridge
Country [47] 0 0
United Kingdom
State/province [47] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Bioverativ Therapeutics Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Swedish Orphan Biovitrum
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT01027364
Trial related presentations / publications
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.
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Bioverativ Therapeutics Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01027364