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

Hemophilia B Clinical Trial

Official title:

A Phase 3b Open-label, Multicenter, Safety and Efficacy Extension Study of a Recombinant Coagulation Factor IX Albumin Fusion Protein (rIX-FP) in Subjects With Hemophilia B

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02053792
• Other study ID #: CSL654_3003
• Secondary ID: 2012-005489-37
• Status: Completed
• Phase: Phase 3
• Start date: February 6, 2014
• Est. completion date: June 2, 2021

Study information

• Verified date: July 2022
• Source: CSL Behring
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 97
• Est. completion date: June 2, 2021
• Est. primary completion date: June 2, 2021
• Accepts healthy volunteers: No
• Gender: Male
• Age group: N/A to 70 Years

Eligibility

Inclusion criteria:

Main study inclusion criteria:

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

Surgery substudy inclusion criterion:

• Must require non-emergency surgery

Subcutaneous substudy inclusion criteria:

• Male, at least 18 years of age.
• Subjects currently enrolled in Study CSL654_3003
• Subjects who have received rIX-FP for = 100 EDs (single-dose cohorts) or for = 50 EDs (repeated-dose cohort) Exclusion criteria:

Main study exclusion criteria:

• 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. The surgical substudy does not have any additional exclusion criteria, although subject(s) in France will not be eligible for the surgery sub-study.

Subcutaneous substudy exclusion criteria:

• 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

Related Conditions & MeSH terms

• Hemophilia A
• Hemophilia B

Intervention

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

Locations

Country	Name	City	State
Australia	Royal Children's Hospital	Parkville	Victoria
Australia	The Children's Hospital Westmead	Westmead	Victoria
Austria	Department of Pediatrics, Medical University of Vienna	Vienna
Austria	Medical University of Vienna, Vienna General Hospital	Vienna
Bulgaria	SHAT "Joan Pavel" ODD [Hemorrhagic Diathesis & Anemia]	Sofia
Canada	McMaster University	Hamilton	Ontario
Czechia	Fakultni nemocnice Brno	Brno
Czechia	Fakultni Nemocrice Ostrava	Ostrava-Poruba
Czechia	Fakultni nemocnice v Motole	Praha
France	CHRU Hopital Morvan	Brest
France	Hopital Louis Pradel	Bron Cedex
France	Hopital Bicetre - Centre de Traitement del'Hemophilia	Le Kremlin-Bicetre
France	Hopital d'Enfants La Timonepital	Marseille Cedex
France	Hopital Necker-Enfants Malades	Paris
Germany	Institut fur experimentelle Hamatologie	Bonn
Germany	Prof. Hess Kinderklinik	Bremen
Germany	CRC Coagulation Research Centre GmbH	Duisburg
Germany	Heinrich Heine University Dusseldorf	Dusseldorf
Germany	Universtatsklinikum Hamburg-Eppendorf	Hamburg
Germany	Werlhof-Institute for Haemostasis and Thrombosis	Hannover
Germany	Kurpfalzkrankenhaus Heidlerberg GmbH	Heidelberg
Israel	Chaim Sheba Medical Center	Tel Aviv
Italy	IRCCS Ospedale Maggiore[Centro emofilia e Trobosi]	Milano
Italy	UOS Gestione e Organizzazione Funzlone Hub Emofilia	Parma
Italy	Centro Malattie Emorragiche e Trombotiche Ospedale	Vicenza
Japan	Nara Medical University Hospital	Kashihara
Japan	University of Occupational and Environmental Health	Kitakyushu
Japan	Nagoya University Hospital	Nagoya
Japan	The Hospital of Hyogo College of Medicine	Nishinomiya
Japan	Ogikubo Hospital	Tokyo
Japan	Tokyo Medical University Hospital	Tokyo
Japan	St. Marianna University, School of Medicine, Seibu Hospital	Yokohama
Malaysia	National Blood Center	Kuala Lumpur
Philippines	Perpetual Succour Hospital	Cebu
South Africa	Haemophilia Comprehensive Care Centre	Parktown
Spain	C.H.U. A Coruna	A Coruna
Spain	Hospital Vall Hebron	Barcelona
Spain	H.U. La Paz	Madrid
United States	University of Colorado	Aurora	Colorado
United States	Indiana Hemophilia & Thrombosis Center Inc.	Indianapolis	Indiana
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of Utah	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
CSL Behring

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Bulgaria,  Canada,  Czechia,  France,  Germany,  Israel,  Italy,  Japan,  Malaysia,  Philippines,  South Africa,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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	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).
Secondary	Spontaneous ABR by Prophylaxis Regimen in PTPs		For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).
Secondary	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.
Secondary	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.
Secondary	Number of Participants With Investigator's Overall Clinical Assessment of Hemostatic Efficacy for the Treatment of Major Bleeding Events With CSL654 in PUPs	The investigator will rate the efficacy of the rIX-FP treatment based on a hemostatic efficacy four point rating scale of excellent, good, moderate, or poor/no response.	Up to 3 years or the time it takes to achieve 50 EDs
Secondary	Total ABR for On-demand Regimen vs. 14-Day Regimen in PTPs		For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).
Secondary	Spontaneous ABR for On-demand Regimen vs. 14-Day Regimen in PTPs		For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).
Secondary	Total ABR for Subjects >=12 Years: 7-Day Regimen vs. 14-Day Regimen in PTPs		For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).
Secondary	Spontaneous ABR for Subjects >=12 Years: 7-Day Regimen vs. 14-Day Regimen in PTPs		For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).
Secondary	Total ABR for Subjects >=12 Years: 7-Day Regimen vs. (10 or 14)-Day Regimen in PTPs		For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).
Secondary	Spontaneous ABR for Subjects >=12 Years: 7-Day Regimen vs. (10 or 14)-Day Regimen in PTPs		For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).