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

• IB1001 (Biological), also known as Recombinant factor IX, IXINITY

Primary outcomes

• Number of Infusions Required for Bleed Control [Treatment Study: at least 50 ED (approximately 6 months); actual mean subject duration: 39.7 ± 12.4 months]

Secondary outcomes

• Area Under the Curve (0-inf) [Pre-infusion to 72 hours following infusion]: Factor IX levels were assessed at the following time points: Pre-infusion, post-infusion at 15-30 min, 4-6 hours, 24-26 hours, 68-72 hours
• Terminal Half-life [Pre-infusion to 72 hours following infusion]: Factor IX levels were assessed at the following time points: Pre-infusion, post-infusion at 15-30 min, 4-6 hours, 24-26 hours, 68-72 hours
• Concentration (Max) [Pre-infusion to 72 hours following infusion]: Factor IX levels were assessed at the following time points: Pre-infusion, post-infusion at 15-30 min, 4-6 hours, 24-26 hours, 68-72 hours
• Incremental Recovery [Pre-infusion to 72 hours following infusion]: Factor IX levels were assessed at the following time points: Pre-infusion, post-infusion at 15-30 min, 4-6 hours, 24-26 hours, 68-72 hours
• Clearance [Pre-infusion to 72 hours following infusion]: Factor IX levels were assessed at the following time points: Pre-infusion, post-infusion at 15-30 min, 4-6 hours, 24-26 hours, 68-72 hours
• Volume of Distribution (Steady State) [Pre-infusion to 72 hours following infusion]: Factor IX levels were assessed at the following time points: Pre-infusion, post-infusion at 15-30 min, 4-6 hours, 24-26 hours, 68-72 hours
• Annualized Bleed Rate [Treatment Study: at least 50 ED (approximately 6 months); actual mean subject duration: 41.7+/- 11.7 Months]: Measure was assessed during the Treatment Study

Sex: All, ages: any to 12 Years

Inclusion Criteria:

1. Subject's parent or legal guardian must give written Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved informed consent and be willing to make the required study visits and follow instructions while enrolled in the study. For subjects ≥7 years of age, assent will be obtained if required by the institution. For subjects < 7 years of age, legal assent is not reasonable to obtain.
2. Severe (factor IX activity ≤2 IU/dL) hemophilia B subjects currently on-demand therapy with a minimum of 2 bleeding episodes requiring factor IX therapy over the preceding 6 months or 4 bleeding episodes over the preceding 12 months; subjects on prophylaxis with a bleeding pattern similar to that 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 50 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 approximately 6 months (50 exposures)
10. Age ≤12 years
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

Participant flow

Outcome results

• Number of Infusions Required for Bleed Control (Primary), Count of units, Number of Infusions: IB1001 4
• Area Under the Curve (0-inf) (Secondary), Mean, IU*hr/dL: IB1001 1062 +/- 322
• Terminal Half-life (Secondary), Mean, hours: IB1001 22.6 +/- 7
• Concentration (Max) (Secondary), Mean, IU/dL: IB1001 51.7 +/- 15.7
• Incremental Recovery (Secondary), Mean, IU/dL per IU/kg: IB1001 0.84 +/- 0.50
• Clearance (Secondary), Mean, mL/(kg*hr): IB1001 7.3 +/- 3.1
• Volume of Distribution (Steady State) (Secondary), Mean, mL/kg: IB1001 244 +/- 166
• Annualized Bleed Rate (Secondary), Median, bleeds/year: IB1001 0.26 (0 to 1.6)

Adverse events

Other adverse events by term

Limitations and caveats: Early termination leading to a small number of subjects analyzed