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

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ClinicalTrials.gov Identifier: NCT00768287
Recruitment Status : Completed
First Posted : October 8, 2008
Results First Posted : September 10, 2018
Last Update Posted : April 12, 2019
Sponsor:
Information provided by (Responsible Party):
Aptevo Therapeutics ( Aptevo BioTherapeutics )

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


Condition or disease Intervention/treatment Phase
Hemophilia B Biological: IB1001 Biological: nonacog alfa Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 77 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
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
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Study Part 1 only
Primary Purpose: Supportive Care
Official Title: Phase I/II/III Pharmacokinetic and Outcome Study of Recombinant Factor IX Product, IB1001, in Subjects With Hemophilia B
Actual Study Start Date : January 2009
Actual Primary Completion Date : March 2013
Actual Study Completion Date : December 2016


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:
  • Recombinant factor IX (rFIX)
  • IXINITY

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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Area Under the Curve (0-inf) [ Time Frame: Pre-infusion to 72 hours following infusion ]
    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.

  2. Area Under the Curve (0-72 hr) [ Time Frame: Pre-infusion to 72 hours following infusion ]
    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.

  3. Terminal Half-life [ Time Frame: Pre-infusion to 72 hours following infusion ]
    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.

  4. Concentration (Max) [ Time Frame: Pre-infusion to 72 hours following infusion ]
    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.

  5. Incremental Recovery [ Time Frame: Pre-infusion to 72 hours following infusion ]
    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.

  6. Mean Residence Time [ Time Frame: Pre-infusion to 72 hours following infusion ]
    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.

  7. Clearance [ Time Frame: Pre-infusion to 72 hours following infusion ]
    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.

  8. Volume of Distribution (Steady State) [ Time Frame: Pre-infusion to 72 hours following infusion ]
    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.

  9. 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 ]
    Measure was assessed during the Treatment Study


Other Outcome Measures:
  1. Blood Loss During Surgery [ Time Frame: During the surgical procedure ]
    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.

  2. Hemostasis Following Surgery [ Time Frame: 12 and 24 hours after 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.

  3. Number of Surgeries Requiring Blood Transfusions [ Time Frame: During the surgical procedure ]
    Measure was assessed during Surgical Substudy.



Information from the National Library of Medicine

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Ages Eligible for Study:   5 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00768287


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Sponsors and Collaborators
Aptevo BioTherapeutics

Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Aptevo BioTherapeutics
ClinicalTrials.gov Identifier: NCT00768287     History of Changes
Other Study ID Numbers: IB1001-01
First Posted: October 8, 2008    Key Record Dates
Results First Posted: September 10, 2018
Last Update Posted: April 12, 2019
Last Verified: April 2019
Additional relevant MeSH terms:
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Hemophilia A
Hemophilia B
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked