Hemophilia BPhase 2/3NCT00768287
Study of Recombinant Factor IX Product, IB1001, in Subjects With Hemophilia B
A Phase 2/3 study testing IB1001 and nonacog alfa in people with Hemophilia B, run by Medexus Pharma, Inc. at 23 sites in 7 countries.
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… Read more about this study
- Who is it for?
- Ages 5 years and older
- Conditions the study is for
- Hemophilia B
- What is being tested?
- IB1001 and nonacog alfa
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 77 participants
- Where
- 23 sitesin 7 countries
- Study dates
- Jan 2009to Dec 2016
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Show all 12Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
23 sites in 7 countries.
23 sites in 7 countries
United States10 sites
Emory University School of Medicine Pediatric Hematology
Atlanta, Georgia, 30322
Rush University Medical Center-Pediatric Hematology Oncology
Chicago, Illinois, 60612
Hemophilia and Thrombosis Center
Cincinnati, Ohio, 45229
City of Hope
Duarte, California, 91010
University of Texas Health Science Center-Houston, Gulf States Hemophilia & Thrombophilia Center
Houston, Texas, 77030
Indiana Hemophilia & Thrombosis Center
Indianapolis, Indiana, 46260
Hemophilia Treatment Center of Las Vegas
Las Vegas, Nevada, 89109
The Hemophilia Treatment Center of Orthopaedic Hospital
Los Angeles, California, 90007
University of Minnesota Center for Bleeding and Clotting Disorder
Minneapolis, Minnesota, 55455
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
United Kingdom5 sites
Centre for Haemostasis and Thrombosis, Basingstoke and North Hampshire Foundation Trust
Basingstoke, Hampshire, RG24 9NA
University Hospital of Wales Health Park
Cardiff, Wales, CF4 4XN
Royal Free Hospital
London, England, NW3 2QG
Manchester Haemophilia Comprehensive Care Manchester Royal Infirmary
Manchester, England, M13 9WL
Royal Hallamshire Hospital
Sheffield, England, S102JF
France2 sites
Hopital Edouard Herriot
Lyon, 69437
Centre Regional de Traitement de l 'Hemophilie
Nantes, Loire-Atlantique, 44093
India2 sites
Sahyadri Specialty Hospital, Deccan Gymkhana
Pune, Maharashtra, 411 004
Jehangir Clinical Development Centre
Pune, Maharashtra, 411 011
Italy2 sites
Ospedale di Careggi
Florence, I-50134
University of Milan
Milan, I-20122
Israel1 site
The National Hemophilia Center-Sheba MC
Tel HaShomer, Ramat Gan, 52621
About this study
Official title: 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
- Conditions
- Hemophilia B
- Being tested
- IB1001, nonacog alfa
- Medical subject headings
- Hemophilia B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IB1001Biological
Also called Recombinant factor IX (rFIX), IXINITY
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 alfaBiological
Also called Recombinant factor IX (rFIX), BeneFIX
Study Part 1: Randomized, double-blind, cross-over study with IB1001 and nonacog alfa
| Study group | Role | What they receive |
|---|---|---|
| IB1001 | Experimental | Not described Receives: Biological: IB1001 |
| nonacog alfa | Active comparator | Not described Receives: Biological: nonacog alfa |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Pre-infusion to 72 hours following infusion
Annualized Bleed Rate
Measure was assessed during the Treatment Study
Measured: Prophylaxis Group Duration of Treatment: 17.9 ± 9.6 months; On Demand Group Duration of Treatment: 15.9 ± 11.5 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2008 (estimated)
- Study startJan 2009
- Primary completionMar 2013
- Study completionDec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Hemophilia BStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Crossover
- 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 77 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medexus Pharma, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00768287
- Sponsor's protocol ID
- IB1001-01
- Status last verified
- Mar 2021
- First submitted
- 7 Oct 2008
- Last updated
- 6 Apr 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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.
PubMed 28833808Martinowitz 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.
PubMed 22764744
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II/III Pharmacokinetic and Outcome Study of Recombinant Factor IX Product, IB1001, in Subjects With Hemophilia B
- ClinicalTrials.gov ID
- NCT00768287
- Acronym / sponsor ID
- IB1001-01
- Conditions
- Hemophilia B
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 77 participants (actual)
- Lead sponsor
- Medexus Pharma, Inc.Industry (pharma, biotech, devices)
- Study start
- Jan 2009 (actual)
- Primary completion
- Mar 2013 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 8 Oct 2008 (estimated)
- Results
- Posted 10 Sep 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- 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
| Arm | Type | Receives |
|---|---|---|
| IB1001 | Experimental | Biological: IB1001 |
| nonacog alfa | Active comparator | Biological: nonacog alfa |
Who may qualify
- Ages
- 5 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IB1001Also: Recombinant factor IX (rFIX), IXINITYStudy 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 | Biological | IB1001 |
| nonacog alfaAlso: Recombinant factor IX (rFIX), BeneFIXStudy Part 1: Randomized, double-blind, cross-over study with IB1001 and nonacog alfa | Biological | nonacog alfa |
Primary outcome
Degree of Hemorrhage Control by Treatment Regimen
Time frame: Prophylaxis Group Duration of Treatment: 17.9 ± 9.6 months; On Demand Group Duration of Treatment: 15.9 ± 11.5 months
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.
9 secondary outcomes
Area Under the Curve (0-inf)
Time frame: Pre-infusion to 72 hours following infusion
Area Under the Curve (0-72 hr)
Time frame: Pre-infusion to 72 hours following infusion
Terminal Half-life
Time frame: Pre-infusion to 72 hours following infusion
Concentration (Max)
Time frame: Pre-infusion to 72 hours following infusion
Incremental Recovery
Time frame: Pre-infusion to 72 hours following infusion
Mean Residence Time
Time frame: Pre-infusion to 72 hours following infusion
Clearance
Time frame: Pre-infusion to 72 hours following infusion
Volume of Distribution (Steady State)
Time frame: Pre-infusion to 72 hours following infusion
Annualized Bleed Rate
Time frame: Prophylaxis Group Duration of Treatment: 17.9 ± 9.6 months; On Demand Group Duration of Treatment: 15.9 ± 11.5 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 28833808Collins 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.
- Derived from this study: PubMed 22764744Martinowitz 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
23 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing IB1001 and nonacog alfa in people with Hemophilia B, run by Medexus Pharma, Inc. at 23 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in United States, United Kingdom, France, India, Italy and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Sep 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Degree of Hemorrhage Control by Treatment Regimen (time frame: Prophylaxis Group Duration of Treatment: 17.9 ± 9.6 months; On Demand Group Duration of Treatment: 15.9 ± 11.5 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00768287, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2021.