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

Hemophilia B Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00768287
• Other study ID #: IB1001-01
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: January 2009
• Est. completion date: December 2016

Study information

• Verified date: March 2021
• Source: Medexus Pharma, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 77
• Est. completion date: December 2016
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hemophilia A
• Hemophilia B

Intervention

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

Locations

Country	Name	City	State
France	Hopital Edouard Herriot	Lyon
France	Centre Regional de Traitement de l 'Hemophilie	Nantes	Loire-Atlantique
India	Jehangir Clinical Development Centre	Pune	Maharashtra
India	Sahyadri Specialty Hospital, Deccan Gymkhana	Pune	Maharashtra
Israel	The National Hemophilia Center-Sheba MC	Tel Hashomer	Ramat Gan
Italy	Ospedale di Careggi	Florence
Italy	University of Milan	Milano
Poland	MTZ Clinical Research	Warsaw
United Kingdom	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	Royal Free Hospital	London	England
United Kingdom	Manchester Haemophilia Comprehensive Care Manchester Royal Infirmary	Manchester	England
United Kingdom	Royal Hallamshire Hospital	Sheffield	England
United States	Emory University School of Medicine Pediatric Hematology	Atlanta	Georgia
United States	Rush University Medical Center-Pediatric Hematology Oncology	Chicago	Illinois
United States	Hemophilia and Thrombosis Center	Cincinnati	Ohio
United States	City of Hope	Duarte	California
United States	University of Texas Health Science Center-Houston, Gulf States Hemophilia & Thrombophilia Center	Houston	Texas
United States	Indiana Hemophilia & Thrombosis Center	Indianapolis	Indiana
United States	Hemophilia Treatment Center of Las Vegas	Las Vegas	Nevada
United States	The Hemophilia Treatment Center of Orthopaedic Hospital	Los Angeles	California
United States	University of Minnesota Center for Bleeding and Clotting Disorder	Minneapolis	Minnesota
United States	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Medexus Pharma, Inc.

Countries where clinical trial is conducted

United States,  France,  India,  Israel,  Italy,  Poland,  United Kingdom, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	Number of Surgeries Requiring Blood Transfusions	Measure was assessed during Surgical Substudy.	During the surgical procedure
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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