Long-Term Safety and Efficacy of rFIXFc in the Prevention and Treatment of Bleeding Episodes in Previously Treated Participants With Hemophilia B (B-YOND)

An Open-Label, Multicenter, Evaluation of the Long-Term Safety and Efficacy of Recombinant Human Coagulation Factor IX Fusion Protein (rFIXFc) in the Prevention and Treatment of Bleeding Episodes in Previously Treated Subjects With Hemophilia B

The primary objective of the study is to evaluate the long-term safety of rFIXFc in participants with hemophilia B.

The secondary objective of this study is to evaluate the efficacy of rFIXFc in the prevention and treatment of bleeding episodes.

Study Overview

• Status: Completed
• Conditions: Severe Hemophilia B
• Intervention / Treatment: Biological: rFIXFc

Detailed Description

Participants will follow either a prophylaxis or on-demand regimen. The starting dose in this study will be determined by the clinical profile of the patient in the preceding studies, B-LONG 998HB102 (NCT01027364) and Kids B-LONG study 9HB02PED (NCT01440946)

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Research Site
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Research Site
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Research Site
    • Perth, Western Australia, Australia, 6008
      • Research Site
• Belgium
  • Bruxelles, Belgium, 1200
    • Research Site
  • Leuven, Belgium, 3000
    • Research Site
• Brazil
  • Sao Paulo
    • Campinas, Sao Paulo, Brazil, 13083-878
      • Research Site
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5B 1W8
      • Research Site
  • Quebec
    • Montreal, Quebec, Canada, H3T 1C5
      • Research Site
• China
  • Beijingshì
    • Beijing, Beijingshì, China, 100005
      • Research Site
  • Guangdongsheng
    • Guangzhou, Guangdongsheng, China, 510515
      • Research Site
  • Shànghaishì
    • Shanghai, Shànghaishì, China, 200025
      • Research Site
  • Tianjinshì
    • Tianjing, Tianjinshì, China, 300020
      • Research Site
• France
  • Bouches-Du-Rhône
    • Marseille, Bouches-Du-Rhône, France, 13385
      • Research Site
• Germany
  • North Rhine-westphalia
    • Bonn, North Rhine-westphalia, Germany, 53127
      • Research Site
• Hong Kong
  • Hong Kong, Hong Kong
    • Research Site
  • New Territories
    • Hong Kong, New Territories, Hong Kong
      • Research Site
• India
  • Karnataka
    • Bangalore, Karnataka, India, 560034
      • Research Site
  • Maharashtra
    • Pune, Maharashtra, India, 411004
      • Research Site
  • Tamil Nadu
    • Vellore, Tamil Nadu, India, 632004
      • Research Site
• Ireland
  • Dublin, Ireland, D12 N512
    • Research Site
• Italy
  • Florence, Italy, 50134
    • Research Site
  • Milano, Italy, 20122
    • Research Site
• Japan
  • Aichi-Ken
    • Nagoya-Shi, Aichi-Ken, Japan, 466-8550
      • Research Site
  • Fukuoka-Ken
    • Kitakyushu, Fukuoka-Ken, Japan, 807-8555
      • Research Site
  • Kanagawa-Ken
    • Kawasaki, Kanagawa-Ken, Japan, 216-8511
      • Research Site
  • Nara-Ken
    • Kashihara-shi, Nara-Ken, Japan, 634-8522
      • Research Site
  • Tokyo-To
    • Shinjuku-ku, Tokyo-To, Japan, 160-0023
      • Research Site
    • Tokyo, Tokyo-To, Japan, 167-8515
      • Research Site
• Netherlands
  • Utrecht, Netherlands, 3584 CX
    • Research Site
• Poland
  • Lodz, Poland, 93-510
    • Research Site
• South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2193
      • Research Site
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7925
      • Research Site
• Sweden
  • Malmö, Sweden, 20502
    • Research Site
  • Stockholm, Sweden, 17176
    • Research Site
• United Kingdom
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
      • Research Site
  • Greater London
    • London, Greater London, United Kingdom, E1 1BB
      • Research Site
    • London, Greater London, United Kingdom, SE1 7EH
      • Research Site
  • Hampshire
    • Basingstoke, Hampshire, United Kingdom, RG24 9NA
      • Research Site
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Research Site
  • California
    • Sacramento, California, United States, 95817
      • Research Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Research Site
  • Hawaii
    • Honolulu, Hawaii, United States, 96826
      • Research Site
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Research Site
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Research Site
  • Michigan
    • East Lansing, Michigan, United States, 48823
      • Research Site
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Research Site
  • Washington
    • Seattle, Washington, United States, 98104
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Key Inclusion Criteria:

• Subjects who have completed studies 998HB102 (NCT01027364) or 9HB02PED (NCT01440946) or other studies with rFIXFc
• Ability to understand the purposes & risks of the study and provide signed and dated informed consent.

Key Exclusion Criteria:

• High-titer inhibitor (>/=5.00 BU/mL)

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: On-Demand; The individual dose of rFIXFc to treat bleeding episodes will be based on participant's clinical condition, type and severity of the bleeding event, and if indicated, Factor IX peak (recovery) levels.	Biological: rFIXFc; Administered as specified in the treatment arm.; Other Names: Alprolix; BIIB029; coagulation factor IX (recombinant) Fc fusion protein
Experimental: Prophylaxis; Weekly prophylaxis, individualized prophylaxis or personalized prophylaxis available.	Biological: rFIXFc; Administered as specified in the treatment arm.; Other Names: Alprolix; BIIB029; coagulation factor IX (recombinant) Fc fusion protein

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Any Positive Inhibitor Development	An inhibitor test result greater than or equal to (>=)0.6 Bethesda units per milliliter (BU/mL), confirmed on 2 separate samples drawn 2 to 4 weeks apart, was considered positive. Both tests were to be performed by the central laboratory using the Nijmegen-modified Bethesda Assay. Data was summarized by treatment regimen for participants from Study 998HB102 and by age cohort (<6 years and 6 to <12 years old) and treatment regimen for participants from Study 9HB02PED per planned analysis. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.	Approximately 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annualized Bleeding Rate (ABR)	ABR is annualized number of bleeding episodes per participant per year. Bleeding episodes were classified as spontaneous if participant records bleeding event when there is no known contributing factor such as definite trauma/antecedent strenuous activity and classified as traumatic if participant records bleeding event when there is known reason for bleed. ABR=(Number of bleeding episodes during efficacy period/number of days during efficacy period)*365.25. Efficacy period reflects sum of all intervals of time during which participants were treated with rFIXFc per treatment regimen excluding major and minor surgical/rehabilitation periods and large injection intervals. ABR was summarized by treatment regimen for participants from study 998HB102 and by age cohort (<6 years and 6 to <12 years old) and treatment regimen for participants from study 9HB02PED per planned analysis. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.	Approximately 5 years
Annualized Spontaneous Joint Bleeding Episodes	Bleeding episodes were classified as spontaneous if participant records a bleeding event when there is no known contributing factor such as definite trauma/antecedent strenuous activity. In addition, location of bleed (joint, internal, skin/mucosa or muscle) were also collected. Annualized spontaneous joint bleeding episodes=(Number of spontaneous joint bleeding episodes during efficacy period/number of days during efficacy period)*365.25. Efficacy period reflects sum of all intervals of time during which participants were treated with rFIXFc per treatment regimen excluding major and minor surgical/rehabilitation periods and large injection intervals. Bleeding episodes were summarized by treatment regimen for participants from study 998HB102 and by age cohort (<6 years and 6 to <12 years old) and treatment regimen for participants from study 9HB02PED as per planned analysis. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.	Approximately 5 years
Total Number of Exposure Days (EDs)	An exposure day is a 24-hour period in which one or more rFIXFc injections are given. The total number of days of exposure to rFIXFc were summarized by treatment regimen for participants from study 998HB102 and by age cohort (<6 years and 6 to <12 years old) and treatment regimen for participants from study 9HB02PED as per planned analysis. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.	Approximately 5 years
Annualized rFIXFc Consumption (International Units Per Kilogram [IU/kg])	Annualized consumption = (total international unit per kilogram [IU/kg] of study treatment received during the efficacy period / total number of days during the efficacy period) multiplied by 365.25. Efficacy period reflects sum of all intervals of time during which participants were treated with rFIXFc per treatment regimen excluding major and minor surgical/rehabilitation periods and large injection intervals. Annualized consumption was summarized by treatment regimen for participants from study 998HB102 and by age cohort (<6 years and 6 to <12 years old) and treatment regimen for participants from study 9HB02PED as per planned analysis. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.	Approximately 5 years
Physicians' Global Assessment of Participant's Response to rFIXFc Regimen Using a 4-Point Scale	Participants were assessed for response to their rFIXFc regimen using following 4-point scale: 1=Excellent: bleeding episodes responded to less than or equal to (<=)usual number of injections or dose of rFIXFc or rate of breakthrough bleeding during prophylaxis was <= that usually observed; 2=Effective: most bleeding episodes responded to same number of injections and dose, but some required more injections or higher doses, or there was minor increase in rate of breakthrough; 3=Partially Effective: bleeding episodes most often required more injections and/or higher doses than expected or adequate breakthrough bleeding prevention during prophylaxis required more frequent injections and/or higher doses and 4=Ineffective: routine failure to control hemostasis/hemostatic control require additional agents. Total number of scale responses =total count of scale responses for all participants; multiple responses per participant including those at scheduled and unscheduled visits are counted.	Approximately 5 years
Participant's Assessment of Response (Excellent or Good Response) to rFIXFc Injections for the Treatment of Bleeding Episodes Using a 4-Point Scale	Using eDiary, participant received rating for treatment response to any bleeding episode (BE) using 4-point scale- 1=Excellent: Abrupt pain relief and/or improvement in signs of bleeding within approximately (approx.) 8 hours (h) after initial injection (inj.); 2=Good: Definite pain relief and/or improvement in signs of bleeding within approx. 8h after an injection, but possibly requiring more than 1 injection after 24-48h for complete resolution; 3=Moderate: Probable/slight beneficial effect within 8h after initial injection and requires more than 1 injection and 4=None: No improvement, or condition worsens within approx. 8h after initial injection. This assessment was to be made approx. 8 to 12h from time the injection was given to treat BE and prior to any additional doses of rFIXFc given for same bleeding episode. Percentages are based on the number of bleeding episodes for which a response (excellent or good) was provided for the first injection during the efficacy period.	Approximately 5 years

Collaborators and Investigators

• Sponsor: Bioverativ Therapeutics Inc.
• Investigators: Study Director: Medical Director, Bioverativ Therapeutics Inc.

Publications and helpful links

General Publications

• Shapiro AD, Pasi KJ, Ozelo MC, Kulkarni R, Barnowski C, Winding B, Szamosi J, Lethagen S. Extending recombinant factor IX Fc fusion protein dosing interval to 14 or more days in patients with hemophilia B. Res Pract Thromb Haemost. 2018 Nov 29;3(1):109-113. doi: 10.1002/rth2.12163. eCollection 2019 Jan.

Study record dates

Study Major Dates

• Study Start (Actual): December 8, 2011
• Primary Completion (Actual): October 1, 2017
• Study Completion (Actual): October 1, 2017

Study Registration Dates

• First Submitted: August 19, 2011
• First Submitted That Met QC Criteria: August 29, 2011
• First Posted (Estimate): August 30, 2011

Study Record Updates

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

More Information

Terms related to this study

• Keywords: B-LONG; B-YOND; B-LONG Extension; rFIXFc; Severe Hemophilia B
• 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: 9HB01EXT; 2011-003075-11