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

NCT01662531 | Completed Phase 3 Results

• 2 other identifiers: CSL654_30022011-006032-23
• Study Type: interventional
• Target: 27
• Locations: 9 countries
• Sites: 16

Brief Summary

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

Conditions

Hemophilia B

Outcome Measures

Primary Outcomes (5)

• Incremental Recovery Following a Single Intravenous Dose of 50 IU/kg rIX-FP or Previous FIX Product

  Incremental recovery (IU/dL/IU/kg) is defined as the FIX activity (IU/dL) obtained 30 minutes following infusion, per dose of (IU/kg) infusion. FIX activity was measured at a central laboratory using validated one-stage clotting method. Recovery values were baseline-corrected for pre-infusion plasma FIX activity. Incremental recovery was measured following a single intravenous dose of 50 IU/kg rIX-FP on Day 1. Analysis of previous FIX product was conducted at the beginning of the study in a subset of subjects who had no historical pharmacokinetic (PK) data of their previous FIX product. For the PK assessment, the previous FIX product was administered by IV infusion after approximately 4 days following the last FIX treatment, prior to any dosing of rIX-FP. The formal PK population consisted of subjects who received at least 1 dose of rIX-FP for PK assessment and for whom a sufficient number of analyzable PK samples had been obtained to permit the evaluation of the PK profile of rIX-FP.

  30 minutes after infusion

• Half-life (t1/2) Following a Single Intravenous Dose of 50 IU/kg rIX-FP or Previous FIX Product

  FIX activity was measured at a central laboratory using validated one-stage clotting method. FIX levels were not corrected for baseline values.

  Pre-dose, 30 minutes, 3, 24, 48, 72 120, 168, 240 and 336 hours post-dose

• Area Under the Concentration Versus Time Curve From Time Point Zero to the Last Sample With Quantifiable Drug Concentration (AUClast)

  AUClast following a single intravenous dose of 50 IU/kg rIX-FP or previous FIX product. FIX activity was measured at a central laboratory using validated one-stage clotting method. FIX levels were not corrected for baseline values.

  Pre-dose, 30 minutes, 3, 24, 48, 72 120, 168, 240 and 336 hours post-dose

• Clearance for FIX Activity Following a Single Intravenous Dose of 50 IU/kg rIX-FP or Previous FIX Product

  FIX activity was measured at a central laboratory using validated one-stage clotting method. FIX levels were not corrected for baseline values. Clearance is normalized for body weight.

  Pre-dose, 30 minutes, 3, 24, 48, 72 120, 168, 240 and 336 hours post-dose

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

  Inhibitor formation was defined as any inhibitor (≥0.6 BU \[Bethesda Units\]/mL) identified and confirmed by retesting.

  12 months

Secondary Outcomes (4)

• Number of Subjects With Treatment-related Adverse Events

  12 months

• Number of Subjects Developing Antibodies Against rIX-FP

  12 months

• Number of Bleeding Episodes Requiring One, Two or More Than Two Infusions of rIX-FP to Achieve Hemostasis

  Approximately 12 months

• Consumption of rIX-FP During Routine Prophylaxis

  12 months

Study Arms (1)

rIX-FP

EXPERIMENTAL

Recombinant Fusion Protein Linking Coagulation Factor IX with Albumin (rIX-FP) will be administered by IV infusion as routine weekly prophylaxis and episodic treatment for bleeding episodes.

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 11 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Male subjects, younger than 12 years old.
• Severe hemophilia B (Factor IX \[FIX\] activity of ≤ 2%).
• Body weight ≥ 10 kg.
• Subjects who have received FIX products (plasma-derived and/or recombinant FIX) for \> 150 exposure days (EDs) (6 to \< 12 years), and \> 50 EDs (\< 6 years).
• 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.

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.
• Kidney or liver disease.
• Recent life-threatening bleeding episode.

Sponsors & Collaborators

• CSL Behring: lead

Study Sites (17)

The Royal Children's Hospital, Melbourne

Parkville, Victoria, 3052, Australia

Location

The Children's Hospital at Westmead

Westmead, 2145, Australia

Location

AKH Wien (Paediatrics)

Vienna, Austria

Location

McMaster Children's Hospital

Hamilton, Ontario, L8N3Z5, Canada

Location

Fakultni nemocnice Brno

Brno, 625 00, Czechia

Location

Fakultni nemocnice Ostrava

Ostrava, 708 52, Czechia

Location

Fakultni nemocnice Motole

Prague, 150 06, Czechia

Location

C.R.T.H. Hopital de Bicentre (Hemophilie)

Le Kremlin-Bicentre, 94275, France

Location

Hospital Edouard Herriot

Lyon, 69437, France

Location

Hôpital d'enfants La Timone

Marseille, 13385, France

Location

CRC Coagulation Research Center GmbH

Duisburg/Altstadt, 47051, Germany

Location

Universitätsklinikum Düsseldorf

Düsseldorf, 40225, Germany

Location

Sheba Medical Center

Tel Litwinsky, 52621, Israel

Location

AOU Careggi

Florence, 50134, Italy

Location

IRCCS Ospendale Maggiore (Centro emofilia e Trombosi)

Milan, 20122, Italy

Location

FGU "Kirov Research Institute of Haemotology and Blood Trans)

Kirov, 610027, Russia

Location

H.U. La Paz

Madrid, 28046, Spain

Location

Related Publications (2)

• Alvarez-Roman MT, Merchan RD, Mellado RCR, Jimenez-Yuste V. Switching and increasing prophylaxis regimen with a genetically recombinant fusion of coagulation factor IX and albumin in haemophilia B: a case report. Curr Opin Hematol. 2023 Sep 1;30(5):175-179. doi: 10.1097/MOH.0000000000000775.

  PMID: 37522479 DERIVED

• Kenet G, Chambost H, Male C, Lambert T, Halimeh S, Chernova T, Mancuso ME, Curtin J, Voigt C, Li Y, Jacobs I, Santagostino E; PROLONG-9FP Investigator Study Group. Long-acting recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in children. Results of a phase 3 trial. Thromb Haemost. 2016 Sep 27;116(4):659-68. doi: 10.1160/TH16-03-0179. Epub 2016 Sep 1.

  PMID: 27583313 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 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2012
• First Posted: August 10, 2012
• Study Start: January 1, 2013
• Primary Completion: October 1, 2014
• Last Updated: May 9, 2016
• Results First Posted: May 9, 2016

Record last verified: 2016-04

Locations

IL (1); ES (1); AU (2); CA (1); DE (2); CZ (3); FR (3); RU (1); IT (2)