Clinical trial NCT00768287: Study of Recombinant Factor IX Product, IB1001, in Subjects With Hemophilia B
Official title: Phase I/II/III Pharmacokinetic and Outcome Study of Recombinant Factor IX Product, IB1001, in Subjects With Hemophilia B
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Hemophilia B
Lead sponsor: Medexus Pharma, Inc.
Sponsor class: INDUSTRY
First posted: 2008-10-08
Enrollment: 77
Sex: ALL
Minimum age (years): 5
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 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
Primary purpose: SUPPORTIVE_CARE

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


Eligibility criteria: 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

Primary outcomes:
measure: Degree of Hemorrhage Control by Treatment Regimen
timeFrame: Prophylaxis Group Duration of Treatment: 17.9 ± 9.6 months; On Demand Group Duration of Treatment: 15.9 ± 11.5 months
Secondary outcomes:
measure: Area Under the Curve (0-inf)
timeFrame: Pre-infusion to 72 hours following infusion
measure: Area Under the Curve (0-72 hr)
timeFrame: Pre-infusion to 72 hours following infusion
measure: Terminal Half-life
timeFrame: Pre-infusion to 72 hours following infusion
measure: Concentration (Max)
timeFrame: Pre-infusion to 72 hours following infusion
measure: Incremental Recovery
timeFrame: Pre-infusion to 72 hours following infusion
measure: Mean Residence Time
timeFrame: Pre-infusion to 72 hours following infusion
measure: Clearance
timeFrame: Pre-infusion to 72 hours following infusion
measure: Volume of Distribution (Steady State)
timeFrame: Pre-infusion to 72 hours following infusion
measure: Annualized Bleed Rate
timeFrame: Prophylaxis Group Duration of Treatment: 17.9 ± 9.6 months; On Demand Group Duration of Treatment: 15.9 ± 11.5 months
Other outcomes:
measure: Blood Loss During Surgery
timeFrame: During the surgical procedure
measure: Hemostasis Following Surgery
timeFrame: 12 and 24 hours after surgery
measure: Number of Surgeries Requiring Blood Transfusions
timeFrame: During the surgical procedure
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Los Angeles
country: United States
facility: The Hemophilia Treatment Center of Orthopaedic Hospital
state: California
city: Atlanta
country: United States
facility: Emory University School of Medicine Pediatric Hematology
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center-Pediatric Hematology Oncology
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Hemophilia & Thrombosis Center
state: Indiana
city: Minneapolis
country: United States
facility: University of Minnesota Center for Bleeding and Clotting Disorder
state: Minnesota
city: Las Vegas
country: United States
facility: Hemophilia Treatment Center of Las Vegas
state: Nevada
city: Cincinnati
country: United States
facility: Hemophilia and Thrombosis Center
state: Ohio
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Houston
country: United States
facility: University of Texas Health Science Center-Houston, Gulf States Hemophilia & Thrombophilia Center
state: Texas
city: Nantes
country: France
facility: Centre Regional de Traitement de l 'Hemophilie
state: Loire-Atlantique
city: Lyon
country: France
facility: Hopital Edouard Herriot
city: Pune
country: India
facility: Sahyadri Specialty Hospital, Deccan Gymkhana
state: Maharashtra
city: Pune
country: India
facility: Jehangir Clinical Development Centre
state: Maharashtra
city: Tel Hashomer
country: Israel
facility: The National Hemophilia Center-Sheba MC
state: Ramat Gan
city: Florence
country: Italy
facility: Ospedale di Careggi
city: Milano
country: Italy
facility: University of Milan
city: Warsaw
country: Poland
facility: MTZ Clinical Research
city: London
country: United Kingdom
facility: Royal Free Hospital
state: England
city: Manchester
country: United Kingdom
facility: Manchester Haemophilia Comprehensive Care Manchester Royal Infirmary
state: England
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital
state: England
city: Basingstoke
country: United Kingdom
facility: Centre for Haemostasis and Thrombosis, Basingstoke and North Hampshire Foundation Trust
state: Hampshire
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales Health Park
state: Wales
Study officials:
References:
citation: 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.
citation: 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.