Trial Outcomes & Findings for Study of Recombinant Factor IX Product, IB1001, in Subjects With Hemophilia B (NCT NCT00768287)

NCT ID: NCT00768287

Last Updated: 2021-04-06

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2/PHASE3
• Target enrollment: 77 participants
• Primary outcome timeframe: Prophylaxis Group Duration of Treatment: 17.9 ± 9.6 months; On Demand Group Duration of Treatment: 15.9 ± 11.5 months
• Results posted on: 2021-04-06

Participant Flow

Subjects could enter the study at any part and could leave at any time. Of the 77 subjects in the total study population, 32 entered during the PK part, 35 entered during the Treatment part, and 10 entered during the Surgical Substudy. Nine subjects participated only in one Part: 3 only in the PK study and 6 only in the Surgical Substudy

Participant milestones

Measure	PK: IB1001 First, Then Nonacog Alfa Pharmacokinetic Study: Randomized, double-blind, cross-over study	PK: Nonacog Alfa First, Then IB1001 Pharmacokinetic Study: Randomized, double-blind, cross-over study	Repeat IB1001 PK Repeat Pharmacokinetic Study: Non-randomized, open-label study	IB1001 Prophylaxis Treatment Study: Non-randomized, open-label study	IB1001 On Demand Treatment Study: Non-randomized, open-label study	IB1001 Surgical Substudy Surgical Substudy: Non-randomized, open-label study
Pharmacokinetic Study STARTED	16	16	0	0	0	0
Pharmacokinetic Study COMPLETED	16	16	0	0	0	0
Pharmacokinetic Study NOT COMPLETED	0	0	0	0	0	0
Repeat Pharmacokinetic Study STARTED	0	0	14	0	0	0
Repeat Pharmacokinetic Study COMPLETED	0	0	14	0	0	0
Repeat Pharmacokinetic Study NOT COMPLETED	0	0	0	0	0	0
Treatment Study STARTED	0	0	0	58	9	0
Treatment Study Treated	0	0	0	61	12	0
Treatment Study COMPLETED	0	0	0	58	9	0
Treatment Study NOT COMPLETED	0	0	0	0	0	0
Surgical Sub-study STARTED	0	0	0	0	0	17
Surgical Sub-study COMPLETED	0	0	0	0	0	17
Surgical Sub-study NOT COMPLETED	0	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	IB1001 Safety Population n=77 Participants Study Population exposed to at least one infusion of IB1001.
Age, Continuous	30.8 years STANDARD_DEVIATION 14.54 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	76 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	73 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race/Ethnicity, Customized Race · American Indian/Alaska Native	0 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian	8 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black or African American	3 Participants n=5 Participants
Race/Ethnicity, Customized Race · Caucasian	61 Participants n=5 Participants
Race/Ethnicity, Customized Race · Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants
Race/Ethnicity, Customized Race · Other	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: Prophylaxis Group Duration of Treatment: 17.9 ± 9.6 months; On Demand Group Duration of Treatment: 15.9 ± 11.5 months

Population: The 68 patients in the Treatment Study (Part 2) were assigned to an initial treatment regimen as follows: prophylaxis (n=58), on demand (n=9), and unassigned (n=1). Patients were allowed to switch regimens during the course of the study. As a result 61 patients were treated with prophylaxis and 12 patients were treated on demand.

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.

Outcome measures

Measure	IB1001 (On Demand) n=222 Bleeding Episodes IB1001 50-100 IU/kg at the time of a bleeding episode	IB1001 (Prophylaxis) n=286 Bleeding Episodes IB1001 50-75 IU/kg twice a week	Repeat IB1001 Repeat PK study of IB1001 75 ± 5 IU/kg 3.1 to 18.6 (median 5.8) months following initial PK study
Degree of Hemorrhage Control by Treatment Regimen Excellent	53 Bleeding Episodes	116 Bleeding Episodes	—
Degree of Hemorrhage Control by Treatment Regimen Good	105 Bleeding Episodes	74 Bleeding Episodes	—
Degree of Hemorrhage Control by Treatment Regimen Fair	25 Bleeding Episodes	28 Bleeding Episodes	—
Degree of Hemorrhage Control by Treatment Regimen Poor	3 Bleeding Episodes	9 Bleeding Episodes	—
Degree of Hemorrhage Control by Treatment Regimen Not Rated	36 Bleeding Episodes	59 Bleeding Episodes	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	IB1001 (On Demand) n=32 Participants IB1001 50-100 IU/kg at the time of a bleeding episode	IB1001 (Prophylaxis) n=32 Participants IB1001 50-75 IU/kg twice a week	Repeat IB1001 n=14 Participants Repeat PK study of IB1001 75 ± 5 IU/kg 3.1 to 18.6 (median 5.8) months following initial PK study
Area Under the Curve (0-inf)	1572.5 IU*hr/dL Standard Deviation 451.5	1656.5 IU*hr/dL Standard Deviation 468.6	1530.0 IU*hr/dL Standard Deviation 435.4

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	IB1001 (On Demand) n=32 Participants IB1001 50-100 IU/kg at the time of a bleeding episode	IB1001 (Prophylaxis) n=32 Participants IB1001 50-75 IU/kg twice a week	Repeat IB1001 n=14 Participants Repeat PK study of IB1001 75 ± 5 IU/kg 3.1 to 18.6 (median 5.8) months following initial PK study
Area Under the Curve (0-72 hr)	1374.6 IU*hr/dL Standard Deviation 356.4	1414.5 IU*hr/dL Standard Deviation 339.4	1355.9 IU*hr/dL Standard Deviation 381.2

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	IB1001 (On Demand) n=32 Participants IB1001 50-100 IU/kg at the time of a bleeding episode	IB1001 (Prophylaxis) n=32 Participants IB1001 50-75 IU/kg twice a week	Repeat IB1001 n=14 Participants Repeat PK study of IB1001 75 ± 5 IU/kg 3.1 to 18.6 (median 5.8) months following initial PK study
Terminal Half-life	24.2 hours Standard Deviation 6.9	26.4 hours Standard Deviation 13.6	24.2 hours Standard Deviation 6.3

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	IB1001 (On Demand) n=32 Participants IB1001 50-100 IU/kg at the time of a bleeding episode	IB1001 (Prophylaxis) n=32 Participants IB1001 50-75 IU/kg twice a week	Repeat IB1001 n=14 Participants Repeat PK study of IB1001 75 ± 5 IU/kg 3.1 to 18.6 (median 5.8) months following initial PK study
Concentration (Max)	73.7 IU/dL Standard Deviation 16.6	72.8 IU/dL Standard Deviation 17.5	72.7 IU/dL Standard Deviation 15.2

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	IB1001 (On Demand) n=32 Participants IB1001 50-100 IU/kg at the time of a bleeding episode	IB1001 (Prophylaxis) n=32 Participants IB1001 50-75 IU/kg twice a week	Repeat IB1001 n=14 Participants Repeat PK study of IB1001 75 ± 5 IU/kg 3.1 to 18.6 (median 5.8) months following initial PK study
Incremental Recovery	0.98 IU/dL per IU/kg Standard Deviation 0.21	0.94 IU/dL per IU/kg Standard Deviation 0.23	0.94 IU/dL per IU/kg Standard Deviation 0.18

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	IB1001 (On Demand) n=32 Participants IB1001 50-100 IU/kg at the time of a bleeding episode	IB1001 (Prophylaxis) n=32 Participants IB1001 50-75 IU/kg twice a week	Repeat IB1001 n=14 Participants Repeat PK study of IB1001 75 ± 5 IU/kg 3.1 to 18.6 (median 5.8) months following initial PK study
Mean Residence Time	31.9 hours Standard Deviation 6.4	35.4 hours Standard Deviation 13.1	30.5 hours Standard Deviation 5.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	IB1001 (On Demand) n=32 Participants IB1001 50-100 IU/kg at the time of a bleeding episode	IB1001 (Prophylaxis) n=32 Participants IB1001 50-75 IU/kg twice a week	Repeat IB1001 n=14 Participants Repeat PK study of IB1001 75 ± 5 IU/kg 3.1 to 18.6 (median 5.8) months following initial PK study
Clearance	0.051 dL/kg*hr Standard Deviation 0.013	0.050 dL/kg*hr Standard Deviation 0.012	0.052 dL/kg*hr Standard Deviation 0.015

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	IB1001 (On Demand) n=32 Participants IB1001 50-100 IU/kg at the time of a bleeding episode	IB1001 (Prophylaxis) n=32 Participants IB1001 50-75 IU/kg twice a week	Repeat IB1001 n=14 Participants Repeat PK study of IB1001 75 ± 5 IU/kg 3.1 to 18.6 (median 5.8) months following initial PK study
Volume of Distribution (Steady State)	1.75 dL/kg Standard Deviation 0.57	1.81 dL/kg Standard Deviation 0.57	1.85 dL/kg Standard Deviation 0.70

SECONDARY outcome

Timeframe: Prophylaxis Group Duration of Treatment: 17.9 ± 9.6 months; On Demand Group Duration of Treatment: 15.9 ± 11.5 months

Population: The 68 patients in the Treatment Study (Part 2) were assigned to an initial treatment regimen as follows: prophylaxis (n=58), on demand (n=9), and unassigned (n=1). Patients were allowed to switch regimens during the course of the study. As a result 61 patients were treated with prophylaxis and 12 patients were treated on demand.

Measure was assessed during the Treatment Study

Outcome measures

Measure	IB1001 (On Demand) n=12 Participants IB1001 50-100 IU/kg at the time of a bleeding episode	IB1001 (Prophylaxis) n=61 Participants IB1001 50-75 IU/kg twice a week	Repeat IB1001 Repeat PK study of IB1001 75 ± 5 IU/kg 3.1 to 18.6 (median 5.8) months following initial PK study
Annualized Bleed Rate	16.10 Bleeds/year Interval 6.6 to 23.7	1.52 Bleeds/year Interval 0.0 to 3.5	—

OTHER_PRE_SPECIFIED outcome

Timeframe: During the surgical procedure

Population: Major surgeries include synovectomy, knee or hip replacement, total tooth extraction, surgery for intracranial hemorrhage, radial head excision, arthrodesis, ankle surgery, abdominal surgery, prostatectomy, or surgery for major muscle bleed repair

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.

Outcome measures

Measure	IB1001 (On Demand) n=19 Major surgeries IB1001 50-100 IU/kg at the time of a bleeding episode	IB1001 (Prophylaxis) IB1001 50-75 IU/kg twice a week	Repeat IB1001 Repeat PK study of IB1001 75 ± 5 IU/kg 3.1 to 18.6 (median 5.8) months following initial PK study
Blood Loss During Surgery Less than expected	6 Major surgeries	—	—
Blood Loss During Surgery Expected	13 Major surgeries	—	—
Blood Loss During Surgery More than expected	0 Major surgeries	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Measure	IB1001 (On Demand) n=19 Major surgeries IB1001 50-100 IU/kg at the time of a bleeding episode	IB1001 (Prophylaxis) n=19 Major surgeries IB1001 50-75 IU/kg twice a week	Repeat IB1001 Repeat PK study of IB1001 75 ± 5 IU/kg 3.1 to 18.6 (median 5.8) months following initial PK study
Hemostasis Following Surgery Superior	7 Major surgeries	7 Major surgeries	—
Hemostasis Following Surgery Adequate	12 Major surgeries	12 Major surgeries	—
Hemostasis Following Surgery Poorly Controlled	0 Major surgeries	0 Major surgeries	—

OTHER_PRE_SPECIFIED outcome

Timeframe: During the surgical procedure

Measure was assessed during Surgical Substudy.

Outcome measures

Measure	IB1001 (On Demand) n=19 Major surgeries IB1001 50-100 IU/kg at the time of a bleeding episode	IB1001 (Prophylaxis) IB1001 50-75 IU/kg twice a week	Repeat IB1001 Repeat PK study of IB1001 75 ± 5 IU/kg 3.1 to 18.6 (median 5.8) months following initial PK study
Number of Surgeries Requiring Blood Transfusions Blood Transfusion Required	0 Major surgeries	—	—
Number of Surgeries Requiring Blood Transfusions No Blood Transfusion Required	19 Major surgeries	—	—

Adverse Events

IB1001 Safety Population

Serious events: 10 serious events

Other events: 58 other events

Deaths: 0 deaths

Serious adverse events

Measure	IB1001 Safety Population n=77 participants at risk Adverse Events were only analyzed for the IB1001 safety population; they were not collected per intervention. The safety population is defined as all subjects who received at least one dose of IB1001 in any part of the study.
Vascular disorders Haematoma	1.3% 1/77 • Number of events 1
Infections and infestations Diverticulitis	1.3% 1/77 • Number of events 3
Injury, poisoning and procedural complications Skin laceration	1.3% 1/77 • Number of events 1
Injury, poisoning and procedural complications Periprosthetic fracture	1.3% 1/77 • Number of events 1
Injury, poisoning and procedural complications Joint injury	1.3% 1/77 • Number of events 1
Injury, poisoning and procedural complications Limb injury	1.3% 1/77 • Number of events 1
Gastrointestinal disorders Abdominal pain	1.3% 1/77 • Number of events 1
Psychiatric disorders Mental status changes	1.3% 1/77 • Number of events 1
Injury, poisoning and procedural complications Lumbar vertebral fracture	1.3% 1/77 • Number of events 1
Infections and infestations Wound infection	1.3% 1/77 • Number of events 1
Injury, poisoning and procedural complications Femur fracture	1.3% 1/77 • Number of events 1
Infections and infestations Postoperative wound infection	1.3% 1/77 • Number of events 1

Other adverse events

Measure	IB1001 Safety Population n=77 participants at risk Adverse Events were only analyzed for the IB1001 safety population; they were not collected per intervention. The safety population is defined as all subjects who received at least one dose of IB1001 in any part of the study.
Gastrointestinal disorders Constipation	5.2% 4/77 • Number of events 8
Gastrointestinal disorders Dairrhoea	9.1% 7/77 • Number of events 7
Gastrointestinal disorders Nausea	5.2% 4/77 • Number of events 6
Gastrointestinal disorders Vomiting	7.8% 6/77 • Number of events 7
General disorders Pyrexia	13.0% 10/77 • Number of events 10
Infections and infestations Nasopharyngitis	11.7% 9/77 • Number of events 18
Injury, poisoning and procedural complications Contusion	5.2% 4/77 • Number of events 7
Injury, poisoning and procedural complications Limb injury	10.4% 8/77 • Number of events 8
Injury, poisoning and procedural complications Procedural pain	5.2% 4/77 • Number of events 6
Musculoskeletal and connective tissue disorders Arthralgia	15.6% 12/77 • Number of events 22
Musculoskeletal and connective tissue disorders Back pain	5.2% 4/77 • Number of events 10
Nervous system disorders Dizziness	6.5% 5/77 • Number of events 9
Nervous system disorders Headache	16.9% 13/77 • Number of events 37
Psychiatric disorders Insomnia	7.8% 6/77 • Number of events 9
Respiratory, thoracic and mediastinal disorders Cough	6.5% 5/77 • Number of events 6
Respiratory, thoracic and mediastinal disorders Nasal congestion	7.8% 6/77 • Number of events 7
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	7.8% 6/77 • Number of events 9
Vascular disorders Hypertension	6.5% 5/77 • Number of events 5
Musculoskeletal and connective tissue disorders Pain in extremity	5.2% 4/77 • Number of events 4
Musculoskeletal and connective tissue disorders Arthritis	5.2% 4/77 • Number of events 4
Injury, poisoning and procedural complications Joint injury	5.2% 4/77 • Number of events 4
Infections and infestations Upper respiratory tract infection	6.5% 5/77 • Number of events 5

Additional Information

Clinical Trial Manager

Medexus Pharma, Inc.

Phone: 1-312-548-3125

Email: julissa.leon@medexus.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place