Study of Recombinant Factor IX Product, IB1001, in Subjects With Hemophilia B

Phase 2

Completed

• Conditions: Hemophilia B
• Interventions: Biological: nonacog alfa; Biological: IB1001

• Registration Number: NCT00768287
• Lead Sponsor: Medexus Pharma, Inc.

Brief Summary

Primary Objective:

To evaluate the safety (acute effects associated with infusions, and inhibitor development), pharmacokinetics (PK), and efficacy with respect to breakthrough bleeding during prophylaxis and with respect to control of hemorrhaging in both the prophylaxis and on demand groups of IB1001 in subjects with hemophilia B.

Key Secondary Objectives:

To evaluate the ability of IB1001 to provide coverage against bleeding under surgical circumstances; To evaluate the long-term safety and efficacy of IB1001

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2008-10-07
• Study First Submitted QC: 2008-10-07
• Study First Posted: 2008-10-08
• Study Start: 2009-01
• Primary Completion: 2013-03
• Study Completion: 2016-12
• Results First Submitted: 2018-03-27
• Results First Submitted QC: 2018-08-09
• Results First Posted: 2018-09-10
• Status Verified: 2021-03
• Last Update Submitted: 2021-03-11
• Last Update Posted: 2021-04-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 77

Inclusion Criteria

1. Patient must be willing to give written Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved informed consent, make the required study visits, and follow instructions while enrolled in the study

2. Severe (factor IX activity ≤2 U/dL) hemophilia B subjects on demand therapy with a minimum of 3 bleeding episodes over the preceding 6 months or 6 bleeding episodes over the preceding 12 months; subjects on prophylaxis with a bleeding pattern as above demonstrated prior to starting prophylaxis

3. Immunocompetent (CD4 count >400/mm3) and not receiving immune modulating or chemotherapeutic agents

4. Previously treated patients with a minimum of 150 exposure days to a factor IX preparation

5. Platelet count at least 150,000/mm3

6. Liver function: alanine transaminase [ALT] and aspartate transaminase [AST] ≤2 times the upper limit of the normal range

7. Total bilirubin ≤1.5 times the upper limit of the normal range

8. Renal function: serum creatinine ≤1.25 times the upper limit of the normal range

9. Willingness to participate in the trial for up to 12-15 months

10. European Union (EU), Israel, and Canada: Age of at least 12 years and body weight of ≥40 kilograms to participate in any PK Study or the Surgical Sub-study [the Surgical Sub-study does not apply to the UK]; age of at least 12 years for the prophylaxis and on demand components of the Treatment Phase and Continuation Study

    United States (US): Age of at least 12 years and body weight of ≥40 kilograms to participate in any PK Study or the Surgical Sub-study; age of at least 5 years for the prophylaxis and on demand components of the Treatment Phase and Continuation Study

11. Hemoglobin ≥7 g/dL at the time of the blood draw

Exclusion Criteria

1. History of factor IX inhibitor ≥0.6 Bethesda units (BU)
2. Existence of another coagulation disorder
3. Evidence of thrombotic disease, fibrinolysis, or disseminated intravascular coagulation (DIC)
4. Use of an investigational drug within 30 days prior to study entry
5. On medications that could impact hemostasis, such as aspirin
6. History of poor compliance, a serious medical or social condition, or any other circumstance that, in the opinion of the investigator, would interfere with participation or compliance with the study protocol
7. History of adverse reaction to either plasma-derived factor IX or recombinant factor IX that interfered with the subject's ability to treat bleeding episodes with a factor IX product

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
nonacog alfa	nonacog alfa	-
IB1001	IB1001	-

Primary Outcome Measures

Name	Time	Method
Degree of Hemorrhage Control by Treatment Regimen	Prophylaxis Group Duration of Treatment: 17.9 ± 9.6 months; On Demand Group Duration of Treatment: 15.9 ± 11.5 months	Subject rating of bleed control within 6 hours of the time bleeding has stopped: 1. Excellent: a dramatic response with abrupt pain relief and clear reduction in joint or hemorrhage site size; 2. Good: pain relief or reduction in hemorrhage site size that may have required an additional infusion for resolution; 3. Fair: probable or slight beneficial response usually requiring one or more additional infusions for resolution; 4. Poor: no improvement or condition worsens.

Secondary Outcome Measures

Name	Time	Method
Concentration (Max)	Pre-infusion to 72 hours following infusion	Factor IX levels were assessed at the following time points: Pre-infusion, post-infusion at 30 min ± 5 min, 1 hour ± 5 min, 3 hours ± 30 min, 6 hours ± 1 hour, 9 hours ± 1 hour, 12 hours ± 2 hours, 24 hours ± 3 hours, 36 hours ± 3 hours, 48 hours ± 3 hours, 60 hours ± 3 hours, and 72 hours ± 3 hours.
Incremental Recovery	Pre-infusion to 72 hours following infusion	Factor IX levels were assessed at the following time points: Pre-infusion, post-infusion at 30 min ± 5 min, 1 hour ± 5 min, 3 hours ± 30 min, 6 hours ± 1 hour, 9 hours ± 1 hour, 12 hours ± 2 hours, 24 hours ± 3 hours, 36 hours ± 3 hours, 48 hours ± 3 hours, 60 hours ± 3 hours, and 72 hours ± 3 hours.
Volume of Distribution (Steady State)	Pre-infusion to 72 hours following infusion	Factor IX levels were assessed at the following time points: Pre-infusion, post-infusion at 30 min ± 5 min, 1 hour ± 5 min, 3 hours ± 30 min, 6 hours ± 1 hour, 9 hours ± 1 hour, 12 hours ± 2 hours, 24 hours ± 3 hours, 36 hours ± 3 hours, 48 hours ± 3 hours, 60 hours ± 3 hours, and 72 hours ± 3 hours.
Area Under the Curve (0-inf)	Pre-infusion to 72 hours following infusion	Factor IX levels were assessed at the following time points: Pre-infusion, post-infusion at 30 min ± 5 min, 1 hour ± 5 min, 3 hours ± 30 min, 6 hours ± 1 hour, 9 hours ± 1 hour, 12 hours ± 2 hours, 24 hours ± 3 hours, 36 hours ± 3 hours, 48 hours ± 3 hours, 60 hours ± 3 hours, and 72 hours ± 3 hours.
Area Under the Curve (0-72 hr)	Pre-infusion to 72 hours following infusion	Factor IX levels were assessed at the following time points: Pre-infusion, post-infusion at 30 min ± 5 min, 1 hour ± 5 min, 3 hours ± 30 min, 6 hours ± 1 hour, 9 hours ± 1 hour, 12 hours ± 2 hours, 24 hours ± 3 hours, 36 hours ± 3 hours, 48 hours ± 3 hours, 60 hours ± 3 hours, and 72 hours ± 3 hours.
Terminal Half-life	Pre-infusion to 72 hours following infusion	Factor IX levels were assessed at the following time points: Pre-infusion, post-infusion at 30 min ± 5 min, 1 hour ± 5 min, 3 hours ± 30 min, 6 hours ± 1 hour, 9 hours ± 1 hour, 12 hours ± 2 hours, 24 hours ± 3 hours, 36 hours ± 3 hours, 48 hours ± 3 hours, 60 hours ± 3 hours, and 72 hours ± 3 hours.
Mean Residence Time	Pre-infusion to 72 hours following infusion	Factor IX levels were assessed at the following time points: Pre-infusion, post-infusion at 30 min ± 5 min, 1 hour ± 5 min, 3 hours ± 30 min, 6 hours ± 1 hour, 9 hours ± 1 hour, 12 hours ± 2 hours, 24 hours ± 3 hours, 36 hours ± 3 hours, 48 hours ± 3 hours, 60 hours ± 3 hours, and 72 hours ± 3 hours.
Clearance	Pre-infusion to 72 hours following infusion	Factor IX levels were assessed at the following time points: Pre-infusion, post-infusion at 30 min ± 5 min, 1 hour ± 5 min, 3 hours ± 30 min, 6 hours ± 1 hour, 9 hours ± 1 hour, 12 hours ± 2 hours, 24 hours ± 3 hours, 36 hours ± 3 hours, 48 hours ± 3 hours, 60 hours ± 3 hours, and 72 hours ± 3 hours.
Annualized Bleed Rate	Prophylaxis Group Duration of Treatment: 17.9 ± 9.6 months; On Demand Group Duration of Treatment: 15.9 ± 11.5 months	Measure was assessed during the Treatment Study

Trial Locations

Locations (23)

The Hemophilia Treatment Center of Orthopaedic Hospital; 🇺🇸 Los Angeles, California, United States

Rush University Medical Center-Pediatric Hematology Oncology; 🇺🇸 Chicago, Illinois, United States

The Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States

Jehangir Clinical Development Centre; 🇮🇳 Pune, Maharashtra, India

Royal Free Hospital; 🇬🇧 London, England, United Kingdom

Manchester Haemophilia Comprehensive Care Manchester Royal Infirmary; 🇬🇧 Manchester, England, United Kingdom

Centre Regional de Traitement de l 'Hemophilie; 🇫🇷 Nantes, Loire-Atlantique, France

Centre for Haemostasis and Thrombosis, Basingstoke and North Hampshire Foundation Trust; 🇬🇧 Basingstoke, Hampshire, United Kingdom

University Hospital of Wales Health Park; 🇬🇧 Cardiff, Wales, United Kingdom

University of Milan; 🇮🇹 Milano, Italy

City of Hope; 🇺🇸 Duarte, California, United States

Emory University School of Medicine Pediatric Hematology; 🇺🇸 Atlanta, Georgia, United States

Indiana Hemophilia & Thrombosis Center; 🇺🇸 Indianapolis, Indiana, United States

University of Minnesota Center for Bleeding and Clotting Disorder; 🇺🇸 Minneapolis, Minnesota, United States

Hemophilia Treatment Center of Las Vegas; 🇺🇸 Las Vegas, Nevada, United States

Hemophilia and Thrombosis Center; 🇺🇸 Cincinnati, Ohio, United States

Sahyadri Specialty Hospital, Deccan Gymkhana; 🇮🇳 Pune, Maharashtra, India

Hopital Edouard Herriot; 🇫🇷 Lyon, France

The National Hemophilia Center-Sheba MC; 🇮🇱 Tel Hashomer, Ramat Gan, Israel

MTZ Clinical Research; 🇵🇱 Warsaw, Poland

Ospedale di Careggi; 🇮🇹 Florence, Italy

Royal Hallamshire Hospital; 🇬🇧 Sheffield, England, United Kingdom

University of Texas Health Science Center-Houston, Gulf States Hemophilia & Thrombophilia Center; 🇺🇸 Houston, Texas, United States