Trial Outcomes & Findings for Post-Marketing Safety Study Following Long-Term Prophylactic OptivateTreatment in Subjects With Severe Haemophilia A (NCT NCT01811875)

NCT ID: NCT01811875

Last Updated: 2021-07-22

Results Overview

FVIII inhibitor status at any of the study visits was measured by a Nijmegen Bethesda assay and inhibitor screens. A result of ≥ 0.6 BU confirmed that the subject had developed inhibitors to FVIII. If this occurred, the test was repeated on a separate sample; if both tests were confirmed to be ≥ 0.6 BU, this was to be reported by the Investigator as a serious adverse event (SAE).

• Recruitment status: TERMINATED
• Study phase: PHASE4
• Target enrollment: 7 participants
• Primary outcome timeframe: At least 100 Exposure Days for each subject. Subjects will attend 5 visits over a period of up to 12 months
• Results posted on: 2021-07-22

Participant Flow

Seven patients were enrolled. One patient in Germany; 4 patients in Colombia and 2 patients in Poland.

Participant milestones

Measure	Optivate 500IU Optivate 500IU Optivate 500IU
Overall Study STARTED	7
Overall Study COMPLETED	5
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Post-Marketing Safety Study Following Long-Term Prophylactic OptivateTreatment in Subjects With Severe Haemophilia A

Baseline characteristics by cohort

Measure	Optivate 500IU n=7 Participants Optivate 500IU Optivate 500IU
Age, Categorical <=18 years	2 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	5 Participants n=93 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants
Age, Continuous	23.6 Years STANDARD_DEVIATION 7.37 • n=93 Participants
Sex: Female, Male Female	0 Participants n=93 Participants
Sex: Female, Male Male	7 Participants n=93 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=93 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=93 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Region of Enrollment Colombia	4 participants n=93 Participants
Region of Enrollment Poland	2 participants n=93 Participants
Region of Enrollment Germany	1 participants n=93 Participants

PRIMARY outcome

Timeframe: At least 100 Exposure Days for each subject. Subjects will attend 5 visits over a period of up to 12 months

Population: Patients who completed at least 100 exposure days to Optivate.

FVIII inhibitor status at any of the study visits was measured by a Nijmegen Bethesda assay and inhibitor screens. A result of ≥ 0.6 BU confirmed that the subject had developed inhibitors to FVIII. If this occurred, the test was repeated on a separate sample; if both tests were confirmed to be ≥ 0.6 BU, this was to be reported by the Investigator as a serious adverse event (SAE).

Outcome measures

Measure	Optivate 500IU n=5 Participants Optivate 500IU Optivate 500IU
Number of Participants That Did Not Develop Inhibitors to FVIII (<0.6BU)	5 Participants

SECONDARY outcome

Timeframe: Screening and Visit 1 (up to 4 weeks)

Population: Recovery with prior FVIII concentrate (Screening Visit) versus first dose with Optivate® (Visit 1) for the protocol population.

Recovery with prior FVIII concentrate (Screening Visit) versus recovery with first dose with Optivate® (Visit 1) for the protocol population.

Outcome measures

Measure	Optivate 500IU n=5 Participants Optivate 500IU Optivate 500IU
Recovery With Prior FVIII Concentrate (Screening Visit) Versus Recovery With First Dose With Optivate® (Visit 1) for the Protocol Population.	-0.91 IU/dL per IU/kg Interval -1.87 to 0.04

SECONDARY outcome

Timeframe: Visits 1 to 4 (Up to 100 Optivate exposure days)

A recovery assessment was conducted at each study visit. Recovery assessments were only conducted after a 3-day washout period and when the subject was not actively bleeding.

At the Screening Visit, subjects who had completed a 3-day washout period and were not actively bleeding were dosed with 30 IU/kg of their prior FVIII concentrate. The dose was measured to the nearest 0.1 mL. Blood samples for the recovery assessment were to be collected at the following time points:

• Predose
• 15 minutes postinfusion (±5 minutes).
• 30 minutes postinfusion (±5 minutes).
• 1 hour postinfusion (±10 minutes). Actual times of sample collection were to be recorded in the CRF

At visits 1, 2, 3 and 4 subjects were dosed with 30 IU/kg of Optivate and blood samples for recovery assessments were taken at the same timepoints as specified above. An ANOVA model (analysis of variance) was used to calculate the adjusted mean for recovery across visits 1 to 4.

Outcome measures

Measure	Optivate 500IU n=5 Participants Optivate 500IU Optivate 500IU
Optivate® Recovery Across Visits 1 to 4 for the Protocol Population.	-0.01 IU/dL per IU/kg Interval -1.72 to 1.7

SECONDARY outcome

Timeframe: Over a period of 12 months

Optivate® therapy to treat number of breakthrough bleeds per subject per year in the protocol population over a period of 12 months.

Outcome measures

Measure	Optivate 500IU n=5 Participants Optivate 500IU Optivate 500IU
Optivate® Therapy to Treat Breakthrough Bleeds Per Subject Per Year in the Protocol Population.	3.99 Bleeds per subject per year Standard Deviation 2.961

SECONDARY outcome

Timeframe: Over a period of 12 months

Overall consumption of Optivate®: Number of exposure days for each subject per year/subject in the per protocol population over a period of 12 months.

Outcome measures

Measure	Optivate 500IU n=5 Participants Optivate 500IU Optivate 500IU
Overall Consumption of Optivate®: Number of Exposure Days for Each Subject Per Year/Subject in the Per Protocol Population.	116.2 Days Standard Deviation 18.12

SECONDARY outcome

Timeframe: Over a period of 12 months

Overall consumption of Optivate®: Total dose in IU/kg of Optivate® per subject for prophylactic use over a period of 12 months.

Outcome measures

Measure	Optivate 500IU n=5 Participants Optivate 500IU Optivate 500IU
Overall Consumption of Optivate®: Total Dose in IU/kg of Optivate® Per Subject for Prophylactic Use.	3639.97 IU/kg Standard Deviation 993.464

SECONDARY outcome

Timeframe: Over a period of 12 months

Overall consumption of Optivate®: Total dose in IU/kg of Optivate® per subject to treat a bleed in the protocol population over a period of 12 months.

Outcome measures

Measure	Optivate 500IU n=5 Participants Optivate 500IU Optivate 500IU
Overall Consumption of Optivate®: Total Dose in IU/kg of Optivate® Per Subject to Treat a Bleed in the Protocol Population.	97.72 IU/kg Standard Deviation 117.086

SECONDARY outcome

Timeframe: Over a period of 12 months

Overall consumption of Optivate®: Total number of infusions for prophylactic use per subject in the protocol population.

Outcome measures

Measure	Optivate 500IU n=5 Participants Optivate 500IU Optivate 500IU
Overall Consumption of Optivate®: Total Number of Infusions for Prophylactic Use Per Subject in the Protocol Population.	116.8 Infusions Standard Deviation 17.66

SECONDARY outcome

Timeframe: Over a period of 12 months

Total number of infusions to treat a bleed per subject in the protocol population.

Outcome measures

Measure	Optivate 500IU n=5 Participants Optivate 500IU Optivate 500IU
Overall Consumption of Optivate®: Total Number of Infusions to Treat a Bleed Per Subject in the Protocol Population.	2.4 Infusions Standard Deviation 3.21

SECONDARY outcome

Timeframe: Over a period of 12 months

Overall consumption of Optivate®: Overall mean dose in IU/kg of Optivate® per subject/year for prophylactic use in the protocol population.

Outcome measures

Measure	Optivate 500IU n=5 Participants Optivate 500IU Optivate 500IU
Overall Consumption of Optivate®: Overall Mean Dose in IU/kg of Optivate® Per Subject/Year for Prophylactic Use in the Protocol Population.	3890.02 IU/kg Standard Deviation 1033.993

SECONDARY outcome

Timeframe: Over a period of 12 months

Population: A total of 3 patients experienced treatment emergent adverse events.

Treatment emergent adverse events (non-serious) in the safety population.

Outcome measures

Measure	Optivate 500IU n=7 Participants Optivate 500IU Optivate 500IU
Treatment Emergent Adverse Events (Non-serious) in the Safety Population	5 treatment emergent events

SECONDARY outcome

Timeframe: Over a period of 12 months

Population: One patient experienced a treatment emergent adverse event (serious).

Treatment emergent adverse events (serious) in safety population over a period of 12 months

Outcome measures

Measure	Optivate 500IU n=7 Participants Optivate 500IU Optivate 500IU
Treatment Emergent Adverse Events (Serious) in Safety Population	1 treatment emergent events

SECONDARY outcome

Timeframe: Over a period of 12 months

Inhibitor Development: Positive FVIII inhibitor status in safety population measured by ≥0.6 Bethesda units (this was a safety measurement but was assessed as a primary efficacy endpoint).

Outcome measures

Measure	Optivate 500IU n=7 Participants Optivate 500IU Optivate 500IU
Number of Participants With Inhibitor Development in Safety Population (Measured by ≥0.6 Bethesda Units)	0 Participants

Adverse Events

Optivate 500IU

Serious events: 2 serious events

Other events: 3 other events

Deaths: 1 deaths

Serious adverse events

Measure	Optivate 500IU n=7 participants at risk Optivate 500IU Optivate 500IU
Injury, poisoning and procedural complications Fatal road traffic accident	14.3% 1/7 • Number of events 1 • Over a period of 12 months Patients had an electronic diary where they could enter any adverse events they experienced in between study visits. Adverse events were assessed at each study visit otherwise. The 9 adverse events (non-serious) recorded include non-treatment emergent and treatment emergent events.
Respiratory, thoracic and mediastinal disorders Asthmatic crisis	14.3% 1/7 • Number of events 1 • Over a period of 12 months Patients had an electronic diary where they could enter any adverse events they experienced in between study visits. Adverse events were assessed at each study visit otherwise. The 9 adverse events (non-serious) recorded include non-treatment emergent and treatment emergent events.

Other adverse events

Measure	Optivate 500IU n=7 participants at risk Optivate 500IU Optivate 500IU
Infections and infestations COMMON COLD	14.3% 1/7 • Number of events 1 • Over a period of 12 months Patients had an electronic diary where they could enter any adverse events they experienced in between study visits. Adverse events were assessed at each study visit otherwise. The 9 adverse events (non-serious) recorded include non-treatment emergent and treatment emergent events.
Injury, poisoning and procedural complications ANKLE TRAUMA	14.3% 1/7 • Number of events 1 • Over a period of 12 months Patients had an electronic diary where they could enter any adverse events they experienced in between study visits. Adverse events were assessed at each study visit otherwise. The 9 adverse events (non-serious) recorded include non-treatment emergent and treatment emergent events.
Respiratory, thoracic and mediastinal disorders BRONCHOSPASM	14.3% 1/7 • Number of events 1 • Over a period of 12 months Patients had an electronic diary where they could enter any adverse events they experienced in between study visits. Adverse events were assessed at each study visit otherwise. The 9 adverse events (non-serious) recorded include non-treatment emergent and treatment emergent events.
Injury, poisoning and procedural complications SOFT TISSUE TRAUMA LEFT HAND	14.3% 1/7 • Number of events 1 • Over a period of 12 months Patients had an electronic diary where they could enter any adverse events they experienced in between study visits. Adverse events were assessed at each study visit otherwise. The 9 adverse events (non-serious) recorded include non-treatment emergent and treatment emergent events.
Blood and lymphatic system disorders ANEMIA	14.3% 1/7 • Number of events 1 • Over a period of 12 months Patients had an electronic diary where they could enter any adverse events they experienced in between study visits. Adverse events were assessed at each study visit otherwise. The 9 adverse events (non-serious) recorded include non-treatment emergent and treatment emergent events.
Musculoskeletal and connective tissue disorders HEMARTHROSIS OF RIGHT ELBOW	14.3% 1/7 • Number of events 1 • Over a period of 12 months Patients had an electronic diary where they could enter any adverse events they experienced in between study visits. Adverse events were assessed at each study visit otherwise. The 9 adverse events (non-serious) recorded include non-treatment emergent and treatment emergent events.
General disorders GENERAL PAIN	14.3% 1/7 • Number of events 1 • Over a period of 12 months Patients had an electronic diary where they could enter any adverse events they experienced in between study visits. Adverse events were assessed at each study visit otherwise. The 9 adverse events (non-serious) recorded include non-treatment emergent and treatment emergent events.
Musculoskeletal and connective tissue disorders JOINT PAIN	14.3% 1/7 • Number of events 1 • Over a period of 12 months Patients had an electronic diary where they could enter any adverse events they experienced in between study visits. Adverse events were assessed at each study visit otherwise. The 9 adverse events (non-serious) recorded include non-treatment emergent and treatment emergent events.
Musculoskeletal and connective tissue disorders HEMARTHROSIS OF RIGHT KNEE	14.3% 1/7 • Number of events 1 • Over a period of 12 months Patients had an electronic diary where they could enter any adverse events they experienced in between study visits. Adverse events were assessed at each study visit otherwise. The 9 adverse events (non-serious) recorded include non-treatment emergent and treatment emergent events.

Additional Information

European Medical Affairs Lead

Bio Products Laboratory Ltd

Phone: +44 20 8957 2200

Email: medinfo@bpl.co.uk

Results disclosure agreements

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