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

NCT00768287 | Completed Phase 2 Results DMC

• 1 other identifier: IB1001-01
• Study Type: interventional
• Target: 77
• Locations: 7 countries
• Sites: 23

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

Conditions

Hemophilia B

Outcome Measures

Primary Outcomes (1)

• Degree of Hemorrhage Control by Treatment Regimen

  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.

  Prophylaxis Group Duration of Treatment: 17.9 ± 9.6 months; On Demand Group Duration of Treatment: 15.9 ± 11.5 months

Secondary Outcomes (9)

• Area Under the Curve (0-inf)

  Pre-infusion to 72 hours following infusion

• Area Under the Curve (0-72 hr)

  Pre-infusion to 72 hours following infusion

• Terminal Half-life

  Pre-infusion to 72 hours following infusion

• Concentration (Max)

  Pre-infusion to 72 hours following infusion

• Incremental Recovery

  Pre-infusion to 72 hours following infusion

Other Outcomes (3)

• Blood Loss During Surgery

  During the surgical procedure

• Hemostasis Following Surgery

  12 and 24 hours after surgery

• Number of Surgeries Requiring Blood Transfusions

  During the surgical procedure

Study Arms (2)

IB1001

EXPERIMENTAL

Biological: IB1001

nonacog alfa

ACTIVE COMPARATOR

Biological: nonacog alfa

Interventions

IB1001 BIOLOGICAL

Study Part 1: Randomized, double-blind, cross-over study with IB1001 and nonacog alfa; Study Part 2: Non-randomized, open-label evaluation of prophylaxis and on demand IB1001; Surgical Sub-study: Open-label evaluation of IB1001 during major surgery

Also known as: Recombinant factor IX (rFIX), IXINITY

IB1001

nonacog alfa BIOLOGICAL

Study Part 1: Randomized, double-blind, cross-over study with IB1001 and nonacog alfa

Also known as: Recombinant factor IX (rFIX), BeneFIX

nonacog alfa

Eligibility Criteria

• Age: 5 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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
• Immunocompetent (CD4 count \>400/mm3) and not receiving immune modulating or chemotherapeutic agents
• Previously treated patients with a minimum of 150 exposure days to a factor IX preparation
• Platelet count at least 150,000/mm3
• Liver function: alanine transaminase \[ALT\] and aspartate transaminase \[AST\] ≤2 times the upper limit of the normal range
• Total bilirubin ≤1.5 times the upper limit of the normal range
• Renal function: serum creatinine ≤1.25 times the upper limit of the normal range
• Willingness to participate in the trial for up to 12-15 months
• 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
• Hemoglobin ≥7 g/dL at the time of the blood draw

You may not qualify if:

• History of factor IX inhibitor ≥0.6 Bethesda units (BU)
• Existence of another coagulation disorder
• Evidence of thrombotic disease, fibrinolysis, or disseminated intravascular coagulation (DIC)
• Use of an investigational drug within 30 days prior to study entry
• On medications that could impact hemostasis, such as aspirin
• 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
• 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

Sponsors & Collaborators

• Medexus Pharma, Inc.: lead

Study Sites (23)

City of Hope

Duarte, California, 91010, United States

Location

The Hemophilia Treatment Center of Orthopaedic Hospital

Los Angeles, California, 90007, United States

Location

Emory University School of Medicine Pediatric Hematology

Atlanta, Georgia, 30322, United States

Location

Rush University Medical Center-Pediatric Hematology Oncology

Chicago, Illinois, 60612, United States

Location

Indiana Hemophilia & Thrombosis Center

Indianapolis, Indiana, 46260, United States

Location

University of Minnesota Center for Bleeding and Clotting Disorder

Minneapolis, Minnesota, 55455, United States

Location

Hemophilia Treatment Center of Las Vegas

Las Vegas, Nevada, 89109, United States

Location

Hemophilia and Thrombosis Center

Cincinnati, Ohio, 45229, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

University of Texas Health Science Center-Houston, Gulf States Hemophilia & Thrombophilia Center

Houston, Texas, 77030, United States

Location

Centre Regional de Traitement de l 'Hemophilie

Nantes, Loire-Atlantique, 44093, France

Location

Hopital Edouard Herriot

Lyon, 69437, France

Location

Sahyadri Specialty Hospital, Deccan Gymkhana

Pune, Maharashtra, 411 004, India

Location

Jehangir Clinical Development Centre

Pune, Maharashtra, 411 011, India

Location

The National Hemophilia Center-Sheba MC

Tel Litwinsky, Ramat Gan, 52621, Israel

Location

Ospedale di Careggi

Florence, I-50134, Italy

Location

University of Milan

Milan, I-20122, Italy

Location

MTZ Clinical Research

Warsaw, 02-106, Poland

Location

Royal Free Hospital

London, England, NW3 2QG, United Kingdom

Location

Manchester Haemophilia Comprehensive Care Manchester Royal Infirmary

Manchester, England, M13 9WL, United Kingdom

Location

Royal Hallamshire Hospital

Sheffield, England, S102JF, United Kingdom

Location

Centre for Haemostasis and Thrombosis, Basingstoke and North Hampshire Foundation Trust

Basingstoke, Hampshire, RG24 9NA, United Kingdom

Location

University Hospital of Wales Health Park

Cardiff, Wales, CF4 4XN, United Kingdom

Location

Related Publications (2)

• Collins PW, Quon DVK, Makris M, Chowdary P, Kempton CL, Apte SJ, Ramanan MV, Hay CRM, Drobic B, Hua Y, Babinchak TJ, Gomperts ED. Pharmacokinetics, safety and efficacy of a recombinant factor IX product, trenonacog alfa in previously treated haemophilia B patients. Haemophilia. 2018 Jan;24(1):104-112. doi: 10.1111/hae.13324. Epub 2017 Aug 17.

  PMID: 28833808 RESULT

• Martinowitz U, Shapiro A, Quon DV, Escobar M, Kempton C, Collins PW, Chowdary P, Makris M, Mannucci PM, Morfini M, Valentino LA, Gomperts E, Lee M. Pharmacokinetic properties of IB1001, an investigational recombinant factor IX, in patients with haemophilia B: repeat pharmacokinetic evaluation and sialylation analysis. Haemophilia. 2012 Nov;18(6):881-7. doi: 10.1111/j.1365-2516.2012.02897.x. Epub 2012 Jul 5.

  PMID: 22764744 DERIVED

MeSH Terms

Conditions

Hemophilia B

Interventions

IB1001; Factor IX

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

Intervention Hierarchy (Ancestors)

Enzyme Precursors; Enzymes and Coenzymes; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Protein Precursors; Biological Factors

Results Point of Contact

• Title: Clinical Trial Manager
• Organization: Medexus Pharma, Inc.

julissa.leon@medexus.com

1-312-548-3125

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Study Part 1 only
• Purpose: SUPPORTIVE CARE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Study Part 1: Randomized, double-blind, cross-over study of pharmacokinetics; Study Part 2: Non-randomized, open-label study of safety and efficacy; Surgical sub-study: Non-randomized, open-label study of safety and efficacy during major surgery

Study Record Dates

• First Submitted: October 7, 2008
• First Posted: October 8, 2008
• Study Start: January 1, 2009
• Primary Completion: March 1, 2013
• Study Completion: December 1, 2016
• Last Updated: April 6, 2021
• Results First Posted: September 10, 2018

Record last verified: 2021-03

Locations

IT (2); IL (1); GB (5); FR (2); US (10); PL (1); IN (2)