A Safety and Efficacy Extension Study of a Recombinant Fusion Protein Linking Coagulation Factor IX With Albumin (rIX-FP) in Patients With Hemophilia B

NCT02053792 | Completed Phase 3 Results

• 2 other identifiers: CSL654_30032012-005489-37
• Study Type: interventional
• Target: 97
• Locations: 14 countries
• Sites: 40

Brief Summary

This study will examine the long-term safety and efficacy of rIX-FP for the control and prevention of bleeding episodes in children and adults with severe hemophilia B. The study will include subjects who have not previously been treated with Factor IX products, subjects who previously completed a CSL-sponsored rIX-FP lead-in study and subjects requiring major non-emergency surgery who have not previously completed a CSL-sponsored rIX-FP lead-in study. A surgical prophylaxis substudy will examine the efficacy of rIX-FP in subjects with hemophilia B who are undergoing non-emergency major or minor surgery. An additional substudy will examine the safety and PK of subcutaneous (SC) administration of rIX-FP.

Conditions

Hemophilia B

Outcome Measures

Primary Outcomes (2)

• Total Number of Participants Who Developed Inhibitors Against Factor IX (FIX)

  For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it takes to achieve 50 EDs.

• Mean Incremental Recovery of a 50 IU/kg Dose of CSL654 in Previously Untreated Patients (PUPs)

  Incremental Recovery: The increase in plasma concentration per IU/kg of factor administered.

  Approximately 30 minutes after infusion of CSL654

Secondary Outcomes (11)

• Total Annualized Bleeding Rate (ABR) by Prophylaxis Regimen in Previously Treated Patients (PTPs)

  For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).

• Spontaneous ABR by Prophylaxis Regimen in PTPs

  For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).

• Average Amount of CSL654 (rIX-FP) Consumed Per Month Per Subject During Routine Prophylaxis Treatment.

  For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it takes to achieve 50 EDs.

• Percentage of Participants With at Least One Treatment Emergent Adverse Event (TEAE) and the Percentage of Participants With at Least One CSL654-related TEAE

  For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it takes to achieve 50 EDs.

• Number of Participants With Investigator's Overall Clinical Assessment of Hemostatic Efficacy for the Treatment of Major Bleeding Events With CSL654 in PUPs

  Up to 3 years or the time it takes to achieve 50 EDs

Study Arms (1)

rIX-FP

EXPERIMENTAL

Subjects will administer rIX-FP by intravenous infusion as routine prophylaxis, prevention, and on-demand treatment during a treatment period of approximately 3 years. The routine prophylaxis treatment interval for previously treated patients may be changed at each scheduled 6-month follow-up assessment. On-demand treatment with rIX-FP will be used for all bleeding episodes requiring treatment. Subjects (other than those in France) may participate in a surgical 'substudy' in which rIX-FP may be administered before, during and after surgery. An additional substudy will examine the safety and PK of subcutaneous administration of rIX-FP. For previously untreated patients, subjects will administer rIX-FP intravenously as weekly prophylaxis and/or on-demand treatment during the first 12 months, and as weekly routine prophylaxis thereafter. The dose of rIX-FP administered will be based on the subject's previous rIX-FP use and/or pharmacokinetic data.

Biological: rIX-FP

Interventions

rIX-FP BIOLOGICAL

Recombinant Fusion Protein Linking Coagulation Factor IX with Albumin (rIX-FP)

rIX-FP

Eligibility Criteria

• Age: Up to 70 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• For previously treated subjects, either:
• Completed a CSL-sponsored rIX-FP (CSL654) study, including study CSL654\_3001 \[NCT01496274\] or study CSL654\_3002 \[NCT01662531\].
• Or:
• Scheduled to have a major non-emergency surgery within approximately 8 weeks from the anticipated date of receiving the first rIX-FP injection.
• Not previously completed a CSL-sponsored rIX-FP lead-in study.
• Male, 12 to 70 years of age.
• Documented severe hemophilia B (FIX activity of ≤ 2%), or confirmed at screening by the central laboratory.
• Subjects who have received FIX products (plasma-derived and / or recombinant FIX) for \> 150 exposure days (EDs), confirmed by their treating physician.
• No confirmed history of FIX inhibitor formation at screening by the central laboratory
• For previously untreated subjects:
• Male, up to 18 years of age.
• Documented severe hemophilia B (FIX activity of ≤ 2%), or confirmed at screening by the central laboratory.
• Never previously been treated with FIX clotting factor products (except previous exposure to blood components).
• No confirmed history of FIX inhibitor formation
• Must require non-emergency surgery

You may not qualify if:

• Currently receiving a therapy not permitted during the study.
• Any issue that, in the opinion of the investigator, would render the subject unsuitable for participation in the study.
• For subjects who have previously completed a CSL-sponsored rIX-FP study:
• Unwilling to participate in the study for a total of 100 exposure days.
• For subjects requiring major non-emergency surgery who have not previously completed a CSL-sponsored rIX-FP lead-in study:
• Known hypersensitivity (ie, allergic reaction or anaphylaxis) to any FIX product or hamster protein.
• Known congenital or acquired coagulation disorder other than congenital FIX deficiency.
• Currently receiving IV immunomodulating agents such as immunoglobulin or chronic systemic corticosteroid treatment.
• Low platelet count, kidney or liver disease.
• Human immunodeficiency virus positive with a CD4 count \< 200/mm3.
• For previously untreated subjects:
• Known congenital or acquired coagulation disorder other than congenital FIX deficiency (except for vitamin K deficiency of the newborn).
• Known kidney or liver dysfunction or any condition which, in the investigator's opinion, place the patient at unjustifiable risk.
• Intravenous use of rIX-FP within 14 days of subcutaneous administration of rIX-FP.
• Life-threatening bleeding episode or major surgery during the 3 months prior to substudy entry

Sponsors & Collaborators

• CSL Behring: lead

Study Sites (42)

University of Colorado

Aurora, Colorado, 80045, United States

Location

Indiana Hemophilia & Thrombosis Center Inc.

Indianapolis, Indiana, 46260, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Utah

Salt Lake City, Utah, 84103, United States

Location

Royal Children's Hospital

Parkville, Victoria, 3052, Australia

Location

The Children's Hospital Westmead

Westmead, Victoria, 2145, Australia

Location

Department of Pediatrics, Medical University of Vienna

Vienna, 1090, Austria

Location

Medical University of Vienna, Vienna General Hospital

Vienna, 1090, Austria

Location

SHAT "Joan Pavel" ODD [Hemorrhagic Diathesis & Anemia]

Sofia, 1233, Bulgaria

Location

McMaster University

Hamilton, Ontario, L8L 2X2, Canada

Location

Fakultni nemocnice Brno

Brno, 62500, Czechia

Location

Fakultni Nemocrice Ostrava

Ostrava-Poruba, 708 52, Czechia

Location

Fakultni nemocnice v Motole

Prague, 15006, Czechia

Location

CHRU Hopital Morvan

Brest, 29609, France

Location

Hopital Louis Pradel

Bron, 69677, France

Location

Hopital Bicetre - Centre de Traitement del'Hemophilia

Le Kremlin-Bicêtre, 94275, France

Location

Hopital d'Enfants La Timonepital

Marseille, 13385, France

Location

Hopital Necker-Enfants Malades

Paris, 75015, France

Location

Institut fur experimentelle Hamatologie

Bonn, 53127, Germany

Location

Prof. Hess Kinderklinik

Bremen, 28177, Germany

Location

CRC Coagulation Research Centre GmbH

Duisburg, 47051, Germany

Location

Heinrich Heine University Dusseldorf

Düsseldorf, 40225, Germany

Location

Universtatsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Werlhof-Institute for Haemostasis and Thrombosis

Hanover, 30159, Germany

Location

Kurpfalzkrankenhaus Heidlerberg GmbH

Heidelberg, Germany

Location

Chaim Sheba Medical Center

Tel Aviv, Israel

Location

IRCCS Ospedale Maggiore[Centro emofilia e Trobosi]

Milan, 20122, Italy

Location

UOS Gestione e Organizzazione Funzlone Hub Emofilia

Parma, 43126, Italy

Location

Centro Malattie Emorragiche e Trombotiche Ospedale

Vicenza, 36100, Italy

Location

Nara Medical University Hospital

Kashihara, 634-8522, Japan

Location

University of Occupational and Environmental Health

Kitakyushu, Japan

Location

Nagoya University Hospital

Nagoya, 466-8550, Japan

Location

The Hospital of Hyogo College of Medicine

Nishinomiya, Japan

Location

Tokyo Medical University Hospital

Tokyo, 160-0023, Japan

Location

Ogikubo Hospital

Tokyo, 167-0035, Japan

Location

St. Marianna University, School of Medicine, Seibu Hospital

Yokohama, 241-0811, Japan

Location

National Blood Center

Kuala Lumpur, 50400, Malaysia

Location

Perpetual Succour Hospital

Cebu, 6000, Philippines

Location

Haemophilia Comprehensive Care Centre

Parktown, 2193, South Africa

Location

C.H.U. A Coruna

A Coruña, Spain

Location

Hospital Vall Hebron

Barcelona, 08035, Spain

Location

H.U. La Paz

Madrid, 28046, Spain

Location

MeSH Terms

Conditions

Hemophilia B

Interventions

albutrepenonacog alfa

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, X-Linked

Results Point of Contact

• Title: Study Director
• Organization: CSL Behring

clinicaltrials@cslbehring.com

610-878-4000

Study Officials

• Program Director

  CSL Behring

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• 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: January 29, 2014
• First Posted: February 4, 2014
• Study Start: February 6, 2014
• Primary Completion: June 2, 2021
• Study Completion: June 2, 2021
• Last Updated: July 14, 2022
• Results First Posted: July 14, 2022

Record last verified: 2022-07

Locations

JP (7); US (4); DE (7); MY (1); IL (1); ZA (1); AU (2); BU (1); ES (3); IT (3); PH (1); CA (1); FR (5); CZ (3)