AzTrials
AzTrials

Severe Hemophilia BPhase 3B-YONDNCT01425723

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

A Phase 3 study testing rFIXFc in people with Severe Hemophilia B, run by Bioverativ Therapeutics Inc. at 49 sites in 18 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Any age, men only
Conditions the study is for
Severe Hemophilia B
What is being tested?
rFIXFc
Could I receive a placebo?
No, everyone receives an active treatment
How many people
120 participants
Where
49 sitesin 18 countries
Study dates
8 Dec 2011to Oct 2017
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • Men only
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • High-titer inhibitor (>/=5.00 BU/mL)
  • NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.

Trial locations and contacts

49 sites in 18 countries.

49 sites in 18 countries

United States10 sites
  • Research Site

    Atlanta, Georgia, 30322

  • Research Site

    Aurora, Colorado, 80045

  • Research Site

    East Lansing, Michigan, 48823

  • Research Site

    Honolulu, Hawaii, 96826

  • Research Site

    Indianapolis, Indiana, 46260

  • Research Site

    New Orleans, Louisiana, 70112

  • Research Site

    Phoenix, Arizona, 85016

  • Research Site

    Pittsburgh, Pennsylvania, 15213

  • Research Site

    Sacramento, California, 95817

  • Research Site

    Seattle, Washington, 98104

Other trials in United States

Japan6 sites
  • Research Site

    Kashihara-shi, Nara, 634-8522

  • Research Site

    Kawasaki, Kanagawa, 216-8511

  • Research Site

    Kitakyushu, Fukuoka, 807-8555

  • Research Site

    Nagoya, Aichi-ken, 466-8550

  • Research Site

    Shinjuku-ku, Tokyo-To, 160-0023

  • Research Site

    Tokyo, Tokyo-To, 167-8515

Other trials in Japan

Australia4 sites
  • Research Site

    Adelaide, South Australia, 5000

  • Research site

    Murdoch, Western Australia, 6150

  • Research site

    Parkville, Victoria, 3052

  • Research Site

    Perth, Western Australia, 6008

Other trials in Australia

China4 sites
  • Research Site

    Beijing, Beijingshì, 100005

  • Research Site

    Guangzhou, Guangdongsheng, 510515

  • Research Site

    Shanghai, Shànghaishì, 200025

  • Research Site

    Tianjing, Tianjinshì, 300020

Other trials in China

United Kingdom4 sites
  • Research Site

    Basingstoke, Hampshire, RG24 9NA

  • Research Site

    Cambridge, Cambridgeshire, CB2 0QQ

  • Research Site

    London, Greater London, E1 1BB

  • Research site

    London, Greater London, SE1 7EH

Other trials in United Kingdom

India3 sites
  • Research Site

    Bangalore, Karnataka, 560034

  • Research Site

    Pune, Maharashtra, 411004

  • Research Site

    Vellore, Tamil Nadu, 632004

Other trials in India

Belgium2 sites
  • Research Site

    Brussels, 1200

  • Research Site

    Leuven, 3000

Other trials in Belgium

Canada2 sites
  • Research Site

    Montreal, Quebec, H3T 1C5

  • Research Site

    Toronto, Ontario, M5B 1W8

Other trials in Canada

Hong Kong2 sites
  • Research Site

    Hong Kong, New Territories

  • Research site

    Hong Kong

Other trials in Hong Kong

Italy2 sites
  • Research Site

    Florence, 50134

  • Research Site

    Milan, 20122

Other trials in Italy

South Africa2 sites
  • Research Site

    Cape Town, Western Cape, 7925

  • Research Site

    Johannesburg, Gauteng, 2193

Other trials in South Africa

Sweden2 sites
  • Research Site

    Malmö, 20502

  • Research Site

    Stockholm, 17176

Other trials in Sweden

Brazil1 site
  • Research Site

    Campinas, São Paulo, 13083-878

Other trials in Brazil

France1 site
  • Research Site

    Marseille, Bouches-Du-Rhône, 13385

Other trials in France

Germany1 site
  • Research Site

    Bonn, North Rhine-Westphalia, 53127

Other trials in Germany

Ireland1 site
  • Research Site

    Dublin, D12 N512

Other trials in Ireland

Netherlands1 site
  • Research Site

    Utrecht, 3584 CX

Other trials in Netherlands

Poland1 site
  • Research Site

    Lodz, 93-510

Other trials in Poland

About this study

Official title: 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.

Read the 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)

Being tested
rFIXFc
Keywords
B-LONG, B-YOND, B-LONG Extension, rFIXFc, Severe Hemophilia B
Medical subject headings
Hemophilia B

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • rFIXFcBiological

    Also called coagulation factor IX (recombinant) Fc fusion protein, Alprolix, BIIB029

    Administered as specified in the treatment arm.

Study groups in NCT01425723
Study groupRoleWhat they receive
On-DemandExperimentalThe 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.
Receives: Biological: rFIXFc
ProphylaxisExperimentalWeekly prophylaxis, individualized prophylaxis or personalized prophylaxis available.
Receives: Biological: rFIXFc

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Approximately 5 years

Secondary outcomes (6)
  1. 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.

    Measured: Approximately 5 years

  2. 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.

    Measured: Approximately 5 years

  3. 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.

    Measured: Approximately 5 years

  4. 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.

    Measured: Approximately 5 years

  5. 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.

    Measured: Approximately 5 years

  6. 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.

    Measured: Approximately 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Aug 2011 (estimated)
  2. Study start8 Dec 2011
  3. Primary completionOct 2017
  4. Study completionOct 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
120 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01425723
Sponsor's protocol ID
9HB01EXT
Other IDs
2011-003075-11
Acronym
B-YOND
Status last verified
Nov 2018
First submitted
19 Aug 2011
Last updated
19 Dec 2020
Data monitoring committee
No

Publications

  • Astermark J, Hermans C, Ezzalfani M, Sidhom A, Barbier S, Kragh N, Falk A, Eriksson D. Recombinant factor IX Fc prophylaxis reduces pain and increases levels of physical activity, with sustained, long-term improvements in patients with hemophilia B: post hoc analysis of phase III trials using patient-reported outcomes. Ther Adv Hematol. 2023 May 29;14:20406207231170701. doi: 10.1177/20406207231170701. eCollection 2023.

    PubMed 37283819
  • Shapiro AD, Kulkarni R, Ragni MV, Chambost H, Mahlangu J, Oldenburg J, Nolan B, Ozelo MC, Foster MC, Willemze A, Barnowski C, Jain N, Winding B, Dumont J, Lethagen S, Barnes C, Pasi KJ. Post hoc longitudinal assessment of the efficacy and safety of recombinant factor IX Fc fusion protein in hemophilia B. Blood Adv. 2023 Jul 11;7(13):3049-3057. doi: 10.1182/bloodadvances.2022009230.

    PubMed 36848635
  • 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.

    PubMed 30656283

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing rFIXFc in people with Severe Hemophilia B, run by Bioverativ Therapeutics Inc. at 49 sites in 18 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 49 sites in United States, Japan, Australia, China, United Kingdom and 13 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Nov 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Any Positive Inhibitor Development (time frame: Approximately 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01425723, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2020.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in