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

Status

Terminated

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01271868

Enrollment

Registered

2011-01-07

Start date

2010-11-30

Completion date

2016-12-31

Last updated

2021-03-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Hemophilia B

Keywords

Recombinant Factor IX

Brief summary

The Study's Primary Objective is to evaluate the pharmacokinetics, safety (acute effects associated with infusions, and inhibitor development) and efficacy (breakthrough bleeding and control of hemorrhaging during prophylaxis) of IB1001 in previously treated pediatric subjects with hemophilia B.

Interventions

BIOLOGICALIB1001

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

No minimum to 12 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame
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

Measure	Time frame	Description
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
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
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
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

Countries

India, United Kingdom, United States

Participant flow

Participants by arm

Arm	Count
IB1001 PK study and Treatment Study	9
Total	9

Baseline characteristics

Characteristic	IB1001
Age, Customized 0 to 5 years	3 years
Age, Customized 6 to 11 years	6 years
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	7 Participants
Race (NIH/OMB) Black or African American	0 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	2 Participants
Sex: Female, Male Female	0 Participants
Sex: Female, Male Male	9 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	9 / 9
serious Total, serious adverse events	0 / 9

Outcome results

Primary

Number of Infusions Required for Bleed Control

Time frame: Treatment Study: at least 50 ED (approximately 6 months); actual mean subject duration: 39.7 ± 12.4 months

Arm	Measure	Category	Value (COUNT_OF_UNITS)
IB1001	Number of Infusions Required for Bleed Control	0 infusions	4 Number of Infusions
IB1001	Number of Infusions Required for Bleed Control	1 infusion	25 Number of Infusions
IB1001	Number of Infusions Required for Bleed Control	2 infusions	1 Number of Infusions
IB1001	Number of Infusions Required for Bleed Control	3 infusions	1 Number of Infusions
IB1001	Number of Infusions Required for Bleed Control	4 infusions	1 Number of Infusions
IB1001	Number of Infusions Required for Bleed Control	5 infusions	1 Number of Infusions

Secondary

Annualized Bleed Rate

Measure was assessed during the Treatment Study

Time frame: Treatment Study: at least 50 ED (approximately 6 months); actual mean subject duration: 41.7+/- 11.7 Months

Arm	Measure	Value (MEDIAN)
IB1001	Annualized Bleed Rate	0.26 bleeds/year

Secondary

Area Under the Curve (0-inf)

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