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

Phase I/II/III Pharmacokinetic and Outcome Study of Recombinant Factor IX Product, IB1001, in Subjects With Hemophilia B

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

Study Overview

• Status: Completed
• Conditions: Hemophilia B
• Intervention / Treatment: Biological: IB1001; Biological: nonacog alfa

• Study Type: Interventional
• Enrollment (Actual): 77
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• France
  • Lyon, France, 69437
    • Hôpital Edouard Herriot
  • Loire-Atlantique
    • Nantes, Loire-Atlantique, France, 44093
      • Centre Regional de Traitement de l 'Hemophilie
• India
  • Maharashtra
    • Pune, Maharashtra, India, 411 004
      • Sahyadri Specialty Hospital, Deccan Gymkhana
    • Pune, Maharashtra, India, 411 011
      • Jehangir Clinical Development Centre
• Israel
  • Ramat Gan
    • Tel Hashomer, Ramat Gan, Israel, 52621
      • The National Hemophilia Center-Sheba MC
• Italy
  • Florence, Italy, I-50134
    • Ospedale di Careggi
  • Milano, Italy, I-20122
    • University of Milan
• Poland
  • Warsaw, Poland, 02-106
    • MTZ Clinical Research
• United Kingdom
  • England
    • London, England, United Kingdom, NW3 2QG
      • Royal Free Hospital
    • Manchester, England, United Kingdom, M13 9WL
      • Manchester Haemophilia Comprehensive Care Manchester Royal Infirmary
    • Sheffield, England, United Kingdom, S102JF
      • Royal Hallamshire Hospital
  • Hampshire
    • Basingstoke, Hampshire, United Kingdom, RG24 9NA
      • Centre for Haemostasis and Thrombosis, Basingstoke and North Hampshire Foundation Trust
  • Wales
    • Cardiff, Wales, United Kingdom, CF4 4XN
      • University Hospital of Wales Health Park
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope
    • Los Angeles, California, United States, 90007
      • The Hemophilia Treatment Center of Orthopaedic Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University School of Medicine Pediatric Hematology
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center-Pediatric Hematology Oncology
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Indiana Hemophilia & Thrombosis center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Center for Bleeding and Clotting Disorder
  • Nevada
    • Las Vegas, Nevada, United States, 89109
      • Hemophilia Treatment Center of Las Vegas
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Hemophilia and Thrombosis Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center-Houston, Gulf States Hemophilia & Thrombophilia Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: IB1001	Biological: IB1001; 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; Other Names: IXINITY; Recombinant factor IX (rFIX)
ACTIVE_COMPARATOR: nonacog alfa	Biological: nonacog alfa; Study Part 1: Randomized, double-blind, cross-over study with IB1001 and nonacog alfa; Other Names: Recombinant factor IX (rFIX); BeneFIX

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Degree of Hemorrhage Control by Treatment Regimen	Subject rating of bleed control within 6 hours of the time bleeding has stopped: Excellent: a dramatic response with abrupt pain relief and clear reduction in joint or hemorrhage site size;; Good: pain relief or reduction in hemorrhage site size that may have required an additional infusion for resolution;; Fair: probable or slight beneficial response usually requiring one or more additional infusions for resolution;; 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve (0-inf)	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.	Pre-infusion to 72 hours following infusion
Area Under the Curve (0-72 hr)	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.	Pre-infusion to 72 hours following infusion
Terminal Half-life	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.	Pre-infusion to 72 hours following infusion
Concentration (Max)	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.	Pre-infusion to 72 hours following infusion
Incremental Recovery	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.	Pre-infusion to 72 hours following infusion
Mean Residence Time	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.	Pre-infusion to 72 hours following infusion
Clearance	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.	Pre-infusion to 72 hours following infusion
Volume of Distribution (Steady State)	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.	Pre-infusion to 72 hours following infusion
Annualized Bleed Rate	Measure was assessed during the Treatment Study	Prophylaxis Group Duration of Treatment: 17.9 ± 9.6 months; On Demand Group Duration of Treatment: 15.9 ± 11.5 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood Loss During Surgery	Surgeon assessment of blood loss during the procedure using the following descriptors: less than expected, expected, or more than expected. Measure was assessed during Surgical Substudy.	During the surgical procedure
Hemostasis Following Surgery	Surgeon assessment of hemostasis at 12 and 24 hours after surgery using the following descriptors: superior, adequate, or poorly controlled. Measure was assessed during Surgical Substudy.	12 and 24 hours after surgery
Number of Surgeries Requiring Blood Transfusions	Measure was assessed during Surgical Substudy.	During the surgical procedure

Collaborators and Investigators

• Sponsor: Medexus Pharma, Inc.

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2009
• Primary Completion (ACTUAL): March 1, 2013
• Study Completion (ACTUAL): December 1, 2016

Study Registration Dates

• First Submitted: October 7, 2008
• First Submitted That Met QC Criteria: October 7, 2008
• First Posted (ESTIMATE): October 8, 2008

Study Record Updates

• Last Update Posted (ACTUAL): April 6, 2021
• Last Update Submitted That Met QC Criteria: March 11, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Blood Coagulation Disorders; Hemophilia A; Hemophilia B
• Other Study ID Numbers: IB1001-01