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

NCT01496274 | Completed Phase 2 Results DMC

• 2 other identifiers: CSL654_30012011-002415-28
• Study Type: interventional
• Target: 63
• Locations: 10 countries
• Sites: 30

Brief Summary

This study will examine the safety, pharmacokinetics and efficacy of rIX-FP for the control and prevention of bleeding episodes in subjects who have previously received factor replacement therapy for hemophilia B.

Conditions

Hemophilia B

Outcome Measures

Primary Outcomes (2)

• Change in Frequency of Spontaneous Bleeding Events Between On-demand and Prophylaxis Treatments (Annualized)

  Subjects in the on-demand arm received on-demand dosing with rIX-FP for up to 26 weeks (on-demand regimen), and then received weekly prophylaxis with rIX-FP for the remainder of the study (prophylaxis regimen). The effectiveness of prophylaxis in comparison to on-demand therapy was investigated by comparing the same subject's annualized spontaneous bleeding rate (AsBR) during the on-demand regimen and during the prophylaxis regimen.

  Up to 26 weeks for on-demand regimen, and between 1 and 17 months for prophylaxis regimen.

• Number of Subjects Developing Inhibitors Against Factor IX (FIX)

  The number of participants developing inhibitors against factor IX (FIX) along with the 95% Clopper-Pearson confidence interval, are summarized for subjects with 50 or more exposure days (EDs) to rIX-FP, and for all participants in the study.

  Up to 27.7 months (maximum)

Secondary Outcomes (11)

• The Frequency of Related Adverse Events

  For the duration of the study; median 20.27 months.

• Number of Subjects Developing Antibodies Against rIX-FP

  For the duration of the study; median 20.27 months.

• Proportion of Bleeding Episodes Requiring One or ≤ Two Injections of rIX-FP to Achieve Hemostasis

  For the duration of the study; median 20.27 months.

• Investigator's Overall Clinical Assessment of Hemostatic Efficacy for Treatment of Bleeding Episodes, Based on a Four Point Ordinal Scales (Excellent, Good, Moderate, Poor/No Response)

  For the duration of the study; median 20.27 months

• rIX-FP Consumed Per Month While Maintaining Assigned Prophylactic Treatment Interval During Routine Prophylaxis.

  Median 269, 240, 386 and 316 days, respectively (see Description)

Study Arms (2)

Prophylaxis

EXPERIMENTAL

Routine weekly prophylaxis and episodic treatment for bleeding episodes. An individualized dosing interval may be tested in sub-group subjects during the 2nd part of the trial. Subjects may participate in a surgical 'sub-study' in which rIX-FP may be administered prior to, during and after surgical intervention.

Biological: rIX-FP

On-demand

EXPERIMENTAL

Episodic treatment for bleeding episodes during the first 6 months then switch to routine weekly prophylaxis for a further 6 months Subjects may participate in a surgical 'sub-study' in which rIX-FP may be administered prior to, during and after surgical intervention.

Biological: rIX-FP

Interventions

rIX-FP BIOLOGICAL

Recombinant IX-FP (rIX-FP) is a fusion protein linking coagulation factor IX with albumin, and will be administered by intravenous administration

On-demand; Prophylaxis

Eligibility Criteria

• Age: 12 Years - 65 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male subjects, 12 to 65 years old
• Severe hemophilia B (FIX activity of ≤ 2%)
• Subjects who have received FIX products (plasma-derived and/or recombinant FIX) for \> 150 exposure days (EDs)
• No history of FIX inhibitor formation, no detectable inhibitors at Screening and no family history of inhibitors against FIX
• Written informed consent for study participation
• On-demand subjects only, who have experienced a minimum average of 2 non-trauma induced bleeding episodes requiring treatment with a FIX product during the previous 6 or 3 months

You may not qualify if:

• Known hypersensitivity to any FIX product or hamster protein
• Known congenital or acquired coagulation disorder other than congenital FIX deficiency
• HIV positive subjects with a CD4 count \< 200/mm3
• Low platelet count, kidney or liver dysfunction
• Recent life-threatening bleeding episode

Sponsors & Collaborators

• CSL Behring: lead

Study Sites (30)

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Indiana Hemophilia and Thrombosis Center, Inc.

Indianapolis, Indiana, 46260, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

BloodCenter of Wisconsin

Milwaukee, Wisconsin, 53201, United States

Location

AKH Wien [Hämatologie, Hämostaseol

Vienna, Austria

Location

SHAT "Joan Pavel" OOD [Hemorrhagic Diathesis and Anemia]

Sofia, 1233, Bulgaria

Location

Centre Hospitalier Universitaire de Brest/CHU Morvan

Brest, 29609, France

Location

C.R.T.H. Hôp. Bicêtre-Hémophilie

Le Kremlin-Bicêtre, 94275, France

Location

CHU de Lyon - Hôpital Edouard Herriot [Hemophilie]

Lyon, 03 69437, France

Location

Hôpital Necker-CRTH

Paris, 75015, France

Location

Instit. für Experimentelle - Hämato & Transfusionsmedizin

Bonn, Germany

Location

Zentralkrankenhaus Prof. Hess-Kinderklinik

Bremen, 28205, Germany

Location

Unikinderklinik Frankfurt/Main [Kinderheilkunde]

Frankfurt, Germany

Location

Universitätsklinikum Hamburg-Eppendorf, Abt für Pädiatr. Hämatologie

Hamburg, 20246, Germany

Location

Werlhof-Inst. Hannover

Hanover, Germany

Location

Chaim Sheba Medical Center

Tel Aviv, Israel

Location

IRCCS Ospedale Maggiore[Centro emofilia e Trombosi]

Milan, Italy

Location

A.O.U. di Parma [Centro di Rif. Reg. per la cura dell'Emofil

Parma, 43126, Italy

Location

Osp. S.Bortolo ULSS N.6 [Terapie Cell. ed Ematologia]

Vicenza, 36100, Italy

Location

Nara Medical University Hospital [PEDIATRICS]

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

Ogikubo Hospital

Tokyo, 167-0035, Japan

Location

Tokyo Medical University Hospital

Tokyo, Japan

Location

St. Marianna University, School of Medicine, Yokohama Seibu

Yokohama, 241-0811, Japan

Location

FGU "Kirov Research Institute of Haemotology and Blood Trans

Kirov, 610027, Russia

Location

C.H.U. A Coruña [Hematología]

A Coruña, Spain

Location

H.U.Vall d'Hebrón [Hemofillia]

Barcelona, Spain

Location

H.U. La Paz [Coagulopatias Congénitas]

Madrid, 28046, Spain

Location

Related Publications (1)

• Santagostino E, Martinowitz U, Lissitchkov T, Pan-Petesch B, Hanabusa H, Oldenburg J, Boggio L, Negrier C, Pabinger I, von Depka Prondzinski M, Altisent C, Castaman G, Yamamoto K, Alvarez-Roman MT, Voigt C, Blackman N, Jacobs I; PROLONG-9FP Investigators Study Group. Long-acting recombinant coagulation factor IX albumin fusion protein (rIX-FP) in hemophilia B: results of a phase 3 trial. Blood. 2016 Apr 7;127(14):1761-9. doi: 10.1182/blood-2015-09-669234. Epub 2016 Jan 11.

  PMID: 26755710 DERIVED

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: Clinical Trial Disclosure Manager
• Organization: CSL Behring

clinicaltrials@cslbehring.com

Use email contact

Study Officials

• Program Director

  CSL Behring

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2011
• First Posted: December 21, 2011
• Study Start: February 1, 2012
• Primary Completion: July 1, 2014
• Last Updated: May 9, 2016
• Results First Posted: May 9, 2016

Record last verified: 2016-04

Locations

US (4); FR (4); IL (1); BU (1); DE (5); JP (7); AU (1); IT (3); RU (1); ES (3)