NCT02234310

Brief Summary

The primary objective of the study was to evaluate the safety of recombinant coagulation factor IX Fc fusion protein (rFIXFc, BIIB029) in previously untreated patients (PUPs) with severe hemophilia B. Secondary objectives were to evaluate the efficacy of rFIXFc in the prevention and treatment of bleeding episodes in PUPs, and to evaluate rFIXFc consumption for prevention and treatment of bleeding episodes in PUPs.

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
33

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Nov 2014

Longer than P75 for phase_3

Geographic Reach
11 countries

27 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 17, 2014

Completed
2 months until next milestone

First Posted

Study publicly available on registry

September 9, 2014

Completed
2 months until next milestone

Study Start

First participant enrolled

November 13, 2014

Completed
4.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 20, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 20, 2019

Completed
12 months until next milestone

Results Posted

Study results publicly available

July 31, 2020

Completed
Last Updated

March 25, 2022

Status Verified

March 1, 2022

Enrollment Period

4.8 years

First QC Date

July 17, 2014

Results QC Date

July 15, 2020

Last Update Submit

March 15, 2022

Conditions

Hemophilia B

Keywords

prophylaxis treatmentepisodic treatment

Outcome Measures

Primary Outcomes (1)

  • Percentage of Participants With Confirmed Inhibitor Development as Measured by the Nijmegen-Modified Bethesda Assay

    Development of an inhibitor was defined as an inhibitor test result of \>= 0.60 Bethesda units per milliliter (BU/mL) that was confirmed by a second test result of \>=0.60 BU/mL from a separate sample, drawn 2 to 4 weeks after the date when the original sample was drawn, with both tests performed by the central laboratory using Nijmegen-modified Bethesda assay.

    Up to 3 years

Secondary Outcomes (8)

  • Annualized Number of Bleeding Episodes (Spontaneous and Traumatic) Per Participant (Annualized Bleeding Rate [ABR])

    Up to 3 years

  • Annualized Number of Spontaneous Joint Bleeding Episodes

    Up to 3 years

  • Number of rFIXFc Injections With Excellent or Good, Moderate or None Treatment Response Assessed Using a 4-Point Scale

    Up to 3 years

  • Total Number of Exposure Days (EDs)

    Up to 3 years

  • Total Annualized rFIXFc Consumption Per Participant for the Prevention and Treatment of Bleeding Episodes

    Up to 3 years

  • +3 more secondary outcomes

Study Arms (1)

Recombinant Coagulation Factor IX Fc Fusion Protein (rFIXFc)

EXPERIMENTAL

Participants received rFIXFc intravenous (IV) injection as follows: Prophylactic treatment regimen: started with rFIXFc 50 International Units per kilogram (IU/kg) weekly until a participant reached at least 50 exposure days (ED=24-hour period in which greater than or equal to (\>=1) injection/dose of rFIXFc was given) to rFIXFc, withdrawal from study or end of study. Adjustments to dose and dosing interval was based on incremental recovery, subsequent Factor IX (FIX) levels, physical activity, bleeding pattern, in accordance with local standards of care for prophylactic regimen (PR). Treatment with episodic (on demand) regimen can be initiated before PR at investigators discretion. Episodic (On demand; optional): rFIXFc at individual doses based on participant's clinical condition, type and severity of bleeding event until PR.

Biological: rFIXFc

Interventions

rFIXFcBIOLOGICAL

Adjustments to the dose and interval of rFIXFc was made in this study based on investigator discretion using available pharmacokinetic (PK) data, subsequent FIX trough and peak levels, level of physical activity, and bleeding pattern, in accordance with local standards of care for a prophylactic regimen. There was an option to start study dosing as episodic treatment (on-demand).

Also known as: BIIB029, Alprolix, recombinant coagulation factor IX Fc fusion protein
Recombinant Coagulation Factor IX Fc Fusion Protein (rFIXFc)

Eligibility Criteria

AgeUp to 17 Years
Sexmale
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • Weight \>=3.5 kilogram at the time of informed consent.
  • Severe hemophilia B was defined as less than or equal to (\<=)2 International Units per deciliter (IU/dL) (\<=2 percent \[%\]) endogenous FIX documented in the medical record or as tested during the Screening Period.

You may not qualify if:

  • History of positive inhibitor testing. A prior history of inhibitors was defined based on a participant's historical positive inhibitor test using the local laboratory Bethesda value for a positive inhibitor test (that is equal to or above lower limit of detection).
  • History of hypersensitivity reactions associated with any rFIXFc administration.
  • Exposure to blood components or injection with a coagulation factor IX (FIX) concentrate (including plasma derived) other than rFIXFc.
  • Injection with commercially available rFIXFc more than 28 days prior to Screening.
  • More than 3 injections of commercially available rFIXFc prior to confirmation of eligibility.
  • Other coagulation disorders in addition to hemophilia B.
  • Any concurrent clinically significant major disease that, in the opinion of the Investigator, would have made the participant unsuitable for enrollment (example HIV infection with cluster of differentiation 4 (CD4) lymphocyte count less than (\<)200 cells/microliter (mcL) or a viral load greater than (\>)200 particles/mcL, or any other known congenital or acquired immunodeficiency).
  • Current systemic treatment with chemotherapy and/or other immunosuppressant drugs. Use of steroids for treatment of asthma or management of acute allergic episodes or otherwise life-threatening episodes was allowed. Treatment in these circumstances should not have exceeded a 14-day duration.
  • Participation within the past 30 days in any other clinical study involving investigational treatment.
  • Current enrollment in any other clinical study involving investigational treatment.
  • Inability to comply with study requirements.
  • Other unspecified reasons that, in the opinion of the Investigator or Bioverativ, would have made the participant unsuitable for enrollment.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (27)

Research Site

Sacramento, California, 95817, United States

Location

Research Site

Washington D.C., District of Columbia, 20010, United States

Location

Research Site

Atlanta, Georgia, 30322, United States

Location

Research Site

Indianapolis, Indiana, 46260, United States

Location

Research Site

Louisville, Kentucky, 40202, United States

Location

Research Site

New Orleans, Louisiana, 70112, United States

Location

Research Site

East Lansing, Michigan, 48823, United States

Location

Research Site

Traverse City, Michigan, 49684, United States

Location

Research Site

Columbus, Ohio, 43205, United States

Location

Research Site

Portland, Oregon, 97239, United States

Location

Research Site

Pittsburgh, Pennsylvania, 15213, United States

Location

Research Site

Westmead, New South Wales, 2145, Australia

Location

Research Site

Aarhus, 8200, Denmark

Location

Hopital Cardiologique - CHU Lille

Lille, Nord, 59037, France

Location

Research Site

Lyon, Rhone, 69437, France

Location

Research Site

Dublin, D12 N512, Ireland

Location

Research Site

Milan, 20122, Italy

Location

Research Site

Napoli, 80122, Italy

Location

Research Site

Parma, 43126, Italy

Location

Research Site

Roma, 00165, Italy

Location

Research Site

Utrecht, 3584 CX, Netherlands

Location

Research Site

Auckland, 1023, New Zealand

Location

Research Site

Warsaw, 02-091, Poland

Location

Research Site

Malmo, 205 02, Sweden

Location

Research Site

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

Location

Research Site

Whitechapel, London, E1 1BB, United Kingdom

Location

Research Site

London, WC1N3JH, United Kingdom

Location

Related Publications (2)

  • Nolan B, Recht M, Rendo P, Falk A, Foster M, Casiano S, Rauch A, Shapiro A. Prophylaxis with recombinant factor IX Fc fusion protein reduces the risk of bleeding and delays time to first spontaneous bleed event in previously untreated patients with haemophilia B: A post hoc analysis of the PUPs B-LONG study. Eur J Haematol. 2024 Oct;113(4):485-492. doi: 10.1111/ejh.14252. Epub 2024 Jun 25.

    PMID: 38922990DERIVED

  • Nolan B, Klukowska A, Shapiro A, Rauch A, Recht M, Ragni M, Curtin J, Gunawardena S, Mukhopadhyay S, Jayawardene D, Winding B, Fischer K, Liesner R. Final results of the PUPs B-LONG study: evaluating safety and efficacy of rFIXFc in previously untreated patients with hemophilia B. Blood Adv. 2021 Jul 13;5(13):2732-2739. doi: 10.1182/bloodadvances.2020004085.

    PMID: 34242387DERIVED

MeSH Terms

Conditions

Hemophilia B

Interventions

factor IX Fc fusion protein

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, InheritedBlood Coagulation DisordersHematologic DiseasesHemic and Lymphatic DiseasesCoagulation Protein DisordersHemorrhagic DisordersGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesGenetic Diseases, X-Linked

Results Point of Contact

Title
Trial Transparency Team
Organization
Bioverativ, a Sanofi company
Contact-US@sanofi.com
800-633-1610

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 17, 2014

First Posted

September 9, 2014

Study Start

November 13, 2014

Primary Completion

August 20, 2019

Study Completion

August 20, 2019

Last Updated

March 25, 2022

Results First Posted

July 31, 2020

Record last verified: 2022-03

Data Sharing

IPD Sharing
Will share

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Locations

GB(3)NL(1)NZ(1)US(11)IT(4)DK(1)PL(1)SE(1)AU(1)FR(2)IE(1)