Back to resultsStudy of Recombinant Factor IX Product, IB1001, in Subjects With Hemophilia B
Primary Purpose
Hemophilia B
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
IB1001
nonacog alfa
Sponsored by
About this trial
This is an interventional supportive care trial for Hemophilia B
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Sites / Locations
- City of Hope
- The Hemophilia Treatment Center of Orthopaedic Hospital
- Emory University School of Medicine Pediatric Hematology
- Rush University Medical Center-Pediatric Hematology Oncology
- Indiana Hemophilia & Thrombosis Center
- University of Minnesota Center for Bleeding and Clotting Disorder
- Hemophilia Treatment Center of Las Vegas
- Hemophilia and Thrombosis Center
- The Children's Hospital of Philadelphia
- University of Texas Health Science Center-Houston, Gulf States Hemophilia & Thrombophilia Center
- Centre Regional de Traitement de l 'Hemophilie
- Hopital Edouard Herriot
- Sahyadri Specialty Hospital, Deccan Gymkhana
- Jehangir Clinical Development Centre
- The National Hemophilia Center-Sheba MC
- Ospedale di Careggi
- University of Milan
- MTZ Clinical Research
- Royal Free Hospital
- Manchester Haemophilia Comprehensive Care Manchester Royal Infirmary
- Royal Hallamshire Hospital
- Centre for Haemostasis and Thrombosis, Basingstoke and North Hampshire Foundation Trust
- University Hospital of Wales Health Park
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
IB1001
nonacog alfa
Arm Description
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
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.
Annualized Bleed Rate
Measure was assessed during the Treatment Study
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00768287
Brief Title
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
2. Study Status
Record Verification Date
March 2021
Overall Recruitment Status
Completed
Study Start Date
January 2009 (Actual)
Primary Completion Date
March 2013 (Actual)
Study Completion Date
December 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Medexus Pharma, Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemophilia B
7. Study Design
Primary Purpose
Supportive Care
Study Phase
Phase 2, Phase 3
Interventional Study Model
Crossover Assignment
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
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Study Part 1 only
Allocation
Randomized
Enrollment
77 (Actual)
8. Arms, Groups, and Interventions
Arm Title
IB1001
Arm Type
Experimental
Arm Title
nonacog alfa
Arm Type
Active Comparator
Intervention Type
Biological
Intervention Name(s)
IB1001
Other Intervention Name(s)
Recombinant factor IX (rFIX), IXINITY
Intervention Description
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
Intervention Type
Biological
Intervention Name(s)
nonacog alfa
Other Intervention Name(s)
Recombinant factor IX (rFIX), BeneFIX
Intervention Description
Study Part 1: Randomized, double-blind, cross-over study with IB1001 and nonacog alfa
Primary Outcome Measure Information:
Title
Degree of Hemorrhage Control by Treatment Regimen
Description
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.
Time Frame
Prophylaxis Group Duration of Treatment: 17.9 ± 9.6 months; On Demand Group Duration of Treatment: 15.9 ± 11.5 months
Secondary Outcome Measure Information:
Title
Area Under the Curve (0-inf)
Description
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.
Time Frame
Pre-infusion to 72 hours following infusion
Title
Area Under the Curve (0-72 hr)
Description
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.
Time Frame
Pre-infusion to 72 hours following infusion
Title
Terminal Half-life
Description
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.
Time Frame
Pre-infusion to 72 hours following infusion
Title
Concentration (Max)
Description
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.
Time Frame
Pre-infusion to 72 hours following infusion
Title
Incremental Recovery
Description
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.
Time Frame
Pre-infusion to 72 hours following infusion
Title
Mean Residence Time
Description
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.
Time Frame
Pre-infusion to 72 hours following infusion
Title
Clearance
Description
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.
Time Frame
Pre-infusion to 72 hours following infusion
Title
Volume of Distribution (Steady State)
Description
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.
Time Frame
Pre-infusion to 72 hours following infusion
Title
Annualized Bleed Rate
Description
Measure was assessed during the Treatment Study
Time Frame
Prophylaxis Group Duration of Treatment: 17.9 ± 9.6 months; On Demand Group Duration of Treatment: 15.9 ± 11.5 months
Other Pre-specified Outcome Measures:
Title
Blood Loss During Surgery
Description
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.
Time Frame
During the surgical procedure
Title
Hemostasis Following Surgery
Description
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.
Time Frame
12 and 24 hours after surgery
Title
Number of Surgeries Requiring Blood Transfusions
Description
Measure was assessed during Surgical Substudy.
Time Frame
During the surgical procedure
10. Eligibility
Sex
All
Minimum Age & Unit of Time
5 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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
Facility Information:
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
The Hemophilia Treatment Center of Orthopaedic Hospital
City
Los Angeles
State/Province
California
ZIP/Postal Code
90007
Country
United States
Facility Name
Emory University School of Medicine Pediatric Hematology
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Rush University Medical Center-Pediatric Hematology Oncology
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Indiana Hemophilia & Thrombosis Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46260
Country
United States
Facility Name
University of Minnesota Center for Bleeding and Clotting Disorder
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Hemophilia Treatment Center of Las Vegas
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89109
Country
United States
Facility Name
Hemophilia and Thrombosis Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
The Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
University of Texas Health Science Center-Houston, Gulf States Hemophilia & Thrombophilia Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Centre Regional de Traitement de l 'Hemophilie
City
Nantes
State/Province
Loire-Atlantique
ZIP/Postal Code
44093
Country
France
Facility Name
Hopital Edouard Herriot
City
Lyon
ZIP/Postal Code
69437
Country
France
Facility Name
Sahyadri Specialty Hospital, Deccan Gymkhana
City
Pune
State/Province
Maharashtra
ZIP/Postal Code
411 004
Country
India
Facility Name
Jehangir Clinical Development Centre
City
Pune
State/Province
Maharashtra
ZIP/Postal Code
411 011
Country
India
Facility Name
The National Hemophilia Center-Sheba MC
City
Tel Hashomer
State/Province
Ramat Gan
ZIP/Postal Code
52621
Country
Israel
Facility Name
Ospedale di Careggi
City
Florence
ZIP/Postal Code
I-50134
Country
Italy
Facility Name
University of Milan
City
Milano
ZIP/Postal Code
I-20122
Country
Italy
Facility Name
MTZ Clinical Research
City
Warsaw
ZIP/Postal Code
02-106
Country
Poland
Facility Name
Royal Free Hospital
City
London
State/Province
England
ZIP/Postal Code
NW3 2QG
Country
United Kingdom
Facility Name
Manchester Haemophilia Comprehensive Care Manchester Royal Infirmary
City
Manchester
State/Province
England
ZIP/Postal Code
M13 9WL
Country
United Kingdom
Facility Name
Royal Hallamshire Hospital
City
Sheffield
State/Province
England
ZIP/Postal Code
S102JF
Country
United Kingdom
Facility Name
Centre for Haemostasis and Thrombosis, Basingstoke and North Hampshire Foundation Trust
City
Basingstoke
State/Province
Hampshire
ZIP/Postal Code
RG24 9NA
Country
United Kingdom
Facility Name
University Hospital of Wales Health Park
City
Cardiff
State/Province
Wales
ZIP/Postal Code
CF4 4XN
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
28833808
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.
Results Reference
result
PubMed Identifier
22764744
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.
Results Reference
derived
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Study of Recombinant Factor IX Product, IB1001, in Subjects With Hemophilia B
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