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

• Sponsor: Bio Products Laboratory (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01811875
• Collaborator: (none)
• Enrollment: 7
• Locations: 4
• Arm: 1
• Actual Duration (Months): 33.3
• Patients Per Site: 1.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Primary objective: To assess post-marketing immunogenicity of Optivate® by monitoring plasma inhibitor levels for at least 100 Exposure Days (EDs) for each subject.

Secondary objectives: To assess efficacy and tolerability by monitoring FVIII recovery and adverse events

Condition or Disease	Intervention/Treatment	Phase
Haemophilia A	Biological: Optivate 500IU	Phase 4

Detailed Description

The primary efficacy endpoint is to assess immunogenicity of Optivate® by monitoring plasma inhibitor level for at least 100 EDs for each subject.

FVIII inhibitor evaluation FVIII inhibitor screen data will be listed. FVIII quantitative inhibitor results will be listed. Shift tables will present the number of subjects with positive (≥ 0.6 BU) and negative (< 0.6 BU) results and those for whom the results change during the study. The number of exposure days until development of inhibitors will be summarised.

For the secondary endpoints: Descriptive statistics will be presented on the number of recoveries at each timepoint and for each subject. These will be presented for each visit and for each subject and then for each batch of FVIII/ Optivate® used. All the AE data (from CRF and study diary) will be pooled together and reported in terms of the type, duration, treatment and/or severity.

Study Design

• Study Type: Interventional
• Actual Enrollment: 7 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Multicentre, Non-controlled, Prospective, Post-Marketing Safety Study Following Long-Term Prophylactic OptivateTreatment in Subjects With Severe Haemophilia A
• Actual Study Start Date: Nov 21, 2014
• Actual Primary Completion Date: Aug 31, 2017
• Actual Study Completion Date: Aug 31, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Optivate 500IU Optivate 500IU	Biological: Optivate 500IU

Outcome Measures

Primary Outcome Measures

1. Number of Participants That Did Not Develop Inhibitors to FVIII (<0.6BU) [At least 100 Exposure Days for each subject. Subjects will attend 5 visits over a period of up to 12 months]

   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).

Secondary Outcome Measures

1. Recovery With Prior FVIII Concentrate (Screening Visit) Versus Recovery With First Dose With Optivate® (Visit 1) for the Protocol Population. [Screening and Visit 1 (up to 4 weeks)]

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

2. Optivate® Recovery Across Visits 1 to 4 for the Protocol Population. [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.

3. Optivate® Therapy to Treat Breakthrough Bleeds Per Subject Per Year in the Protocol Population. [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.

4. 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]

   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.

5. Overall Consumption of Optivate®: Total Dose in IU/kg of Optivate® Per Subject for Prophylactic Use. [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.

6. 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]

   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.

7. Overall Consumption of Optivate®: Total Number of Infusions for Prophylactic Use Per Subject in the Protocol Population. [Over a period of 12 months]

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

8. Overall Consumption of Optivate®: Total Number of Infusions to Treat a Bleed Per Subject in the Protocol Population. [Over a period of 12 months]

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

9. Overall Consumption of Optivate®: Overall Mean Dose in IU/kg of Optivate® Per Subject/Year for Prophylactic Use in the Protocol Population. [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.

10. Treatment Emergent Adverse Events (Non-serious) in the Safety Population [Over a period of 12 months]

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

11. Treatment Emergent Adverse Events (Serious) in Safety Population [Over a period of 12 months]

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

12. Number of Participants With Inhibitor Development in Safety Population (Measured by ≥0.6 Bethesda Units) [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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Written informed consent or, if less than 18 years of age written assent (where possible) and their parent/guardian's written informed consent.

• Severe haemophilia A (< 1%# FVIII:C).

• Previously Treated Patients (PTPs) with > 150 exposure days on prior Factor VIII therapy (of which at least the last 50 EDs or 2 years treatment can be confirmed by way of subject records).

• Immunocompetent with CD4 count > 200 / µl.

• HIV negative or a viral load < 200 particles / µl.

• subjects suffering from severe haemophilia A (<2%) may be enrolled, but only after approval by BPL. Subjects with a Factor VIII of <2% may not constitute more than 50% of the total patient population. A separate statistical evaluation will be conducted for the <1% and <2% populations.

Exclusion Criteria:

• • History of inhibitor development to FVIII or a positive result on the Nijmegen Bethesda at screening (quantitative result of > 0.6 BU) prior to the administration of Optivate®.

• Known or suspected hypersensitivity to the investigational medicinal product or its excipients.

• Clinically significant liver disease, renal disease, or coagulopathy other than haemophilia A.

• History of unreliability or non cooperation (including not being able to complete the study diary).

• Participating in, or have taken part in another trial within the last 30 days.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fundacion BIOS	Barranquilla		Colombia	80-216
2	Hospital general de Medellin	Medellin		Colombia	32-102
3	HZRM Haemophilia Centre Rhine Main	Darmstadt	Mörfelden-Walldorf	Germany	64546
4	Wojewodzki Szpital Specjalistyczny im. M. Kopernika	Lodz		Poland	93-513

Sponsors and Collaborators

• Bio Products Laboratory

Investigators

• Study Director: Eric Wolford, Bio Products Laboratory

Study Documents (Full-Text)

• Study Protocol - Nov 30, 2015
• Statistical Analysis Plan - May 21, 2013

More Information

Publications

None provided.

• Responsible Party: Bio Products Laboratory
• ClinicalTrials.gov Identifier: NCT01811875
• Other Study ID Numbers: 8VWF07
• First Posted: Mar 15, 2013
• Last Update Posted: Jul 22, 2021
• Last Verified: Jul 1, 2021

• Keywords provided by Bio Products Laboratory: Haemophilia A
• Additional relevant MeSH terms: Hemophilia A

Study Results

Participant Flow

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

Arm/Group Title	Optivate 500IU
Arm/Group Description	Optivate 500IU Optivate 500IU
Period Title: Overall Study
STARTED	7
COMPLETED	5
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Optivate 500IU
Arm/Group Description	Optivate 500IU Optivate 500IU
Overall Participants	7
Age (Count of Participants)
<=18 years	2 28.6%
Between 18 and 65 years	5 71.4%
>=65 years	0 0%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	23.6 (7.37)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	7 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 71.4%
Not Hispanic or Latino	2 28.6%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
Colombia	4 57.1%
Poland	2 28.6%
Germany	1 14.3%

Outcome Measures

1. Primary Outcome

Title	Number of Participants That Did Not Develop Inhibitors to FVIII (<0.6BU)
Description	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).
Time Frame	At least 100 Exposure Days for each subject. Subjects will attend 5 visits over a period of up to 12 months

Outcome Measure Data

Analysis Population Description

Patients who completed at least 100 exposure days to Optivate.

Arm/Group Title	Optivate 500IU
Arm/Group Description	Optivate 500IU Optivate 500IU
Measure Participants	5
Count of Participants [Participants]	5 71.4%

2. Secondary Outcome

Title	Recovery With Prior FVIII Concentrate (Screening Visit) Versus Recovery With First Dose With Optivate® (Visit 1) for the Protocol Population.
Description	Recovery with prior FVIII concentrate (Screening Visit) versus recovery with first dose with Optivate® (Visit 1) for the protocol population.
Time Frame	Screening and Visit 1 (up to 4 weeks)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Optivate 500IU
Arm/Group Description	Optivate 500IU Optivate 500IU
Measure Participants	5
Mean (95% Confidence Interval) [IU/dL per IU/kg]	-0.91

3. Secondary Outcome

Title	Optivate® Recovery Across Visits 1 to 4 for the Protocol Population.
Description	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.
Time Frame	Visits 1 to 4 (Up to 100 Optivate exposure days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Optivate 500IU
Arm/Group Description	Optivate 500IU Optivate 500IU
Measure Participants	5
Mean (95% Confidence Interval) [IU/dL per IU/kg]	-0.01

4. Secondary Outcome

Title	Optivate® Therapy to Treat Breakthrough Bleeds Per Subject Per Year in the Protocol Population.
Description	Optivate® therapy to treat number of breakthrough bleeds per subject per year in the protocol population over a period of 12 months.
Time Frame	Over a period of 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Optivate 500IU
Arm/Group Description	Optivate 500IU Optivate 500IU
Measure Participants	5
Mean (Standard Deviation) [Bleeds per subject per year]	3.99 (2.961)

5. Secondary Outcome

Title	Overall Consumption of Optivate®: Number of Exposure Days for Each Subject Per Year/Subject in the Per Protocol Population.
Description	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.
Time Frame	Over a period of 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Optivate 500IU
Arm/Group Description	Optivate 500IU Optivate 500IU
Measure Participants	5
Mean (Standard Deviation) [Days]	116.2 (18.12)

6. Secondary Outcome

Title	Overall Consumption of Optivate®: Total Dose in IU/kg of Optivate® Per Subject for Prophylactic Use.
Description	Overall consumption of Optivate®: Total dose in IU/kg of Optivate® per subject for prophylactic use over a period of 12 months.
Time Frame	Over a period of 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Optivate 500IU
Arm/Group Description	Optivate 500IU Optivate 500IU
Measure Participants	5
Mean (Standard Deviation) [IU/kg]	3639.97 (993.464)

7. Secondary Outcome

Title	Overall Consumption of Optivate®: Total Dose in IU/kg of Optivate® Per Subject to Treat a Bleed in the Protocol Population.
Description	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.
Time Frame	Over a period of 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Optivate 500IU
Arm/Group Description	Optivate 500IU Optivate 500IU
Measure Participants	5
Mean (Standard Deviation) [IU/kg]	97.72 (117.086)

8. Secondary Outcome

Title	Overall Consumption of Optivate®: Total Number of Infusions for Prophylactic Use Per Subject in the Protocol Population.
Description	Overall consumption of Optivate®: Total number of infusions for prophylactic use per subject in the protocol population.
Time Frame	Over a period of 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Optivate 500IU
Arm/Group Description	Optivate 500IU Optivate 500IU
Measure Participants	5
Mean (Standard Deviation) [Infusions]	116.8 (17.66)

9. Secondary Outcome

Title	Overall Consumption of Optivate®: Total Number of Infusions to Treat a Bleed Per Subject in the Protocol Population.
Description	Total number of infusions to treat a bleed per subject in the protocol population.
Time Frame	Over a period of 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Optivate 500IU
Arm/Group Description	Optivate 500IU Optivate 500IU
Measure Participants	5
Mean (Standard Deviation) [Infusions]	2.4 (3.21)

10. Secondary Outcome

Title	Overall Consumption of Optivate®: Overall Mean Dose in IU/kg of Optivate® Per Subject/Year for Prophylactic Use in the Protocol Population.
Description	Overall consumption of Optivate®: Overall mean dose in IU/kg of Optivate® per subject/year for prophylactic use in the protocol population.
Time Frame	Over a period of 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Optivate 500IU
Arm/Group Description	Optivate 500IU Optivate 500IU
Measure Participants	5
Mean (Standard Deviation) [IU/kg]	3890.02 (1033.993)

11. Secondary Outcome

Title	Treatment Emergent Adverse Events (Non-serious) in the Safety Population
Description	Treatment emergent adverse events (non-serious) in the safety population.
Time Frame	Over a period of 12 months

Outcome Measure Data

Analysis Population Description

A total of 3 patients experienced treatment emergent adverse events.

Arm/Group Title	Optivate 500IU
Arm/Group Description	Optivate 500IU Optivate 500IU
Measure Participants	7
Number [treatment emergent events]	5

12. Secondary Outcome

Title	Treatment Emergent Adverse Events (Serious) in Safety Population
Description	Treatment emergent adverse events (serious) in safety population over a period of 12 months
Time Frame	Over a period of 12 months

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Optivate 500IU
Arm/Group Description	Optivate 500IU Optivate 500IU
Measure Participants	7
Number [treatment emergent events]	1

13. Secondary Outcome

Title	Number of Participants With Inhibitor Development in Safety Population (Measured by ≥0.6 Bethesda Units)
Description	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).
Time Frame	Over a period of 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Optivate 500IU
Arm/Group Description	Optivate 500IU Optivate 500IU
Measure Participants	7
Count of Participants [Participants]	0 0%

Adverse Events

Time Frame	Over a period of 12 months
Adverse Event Reporting Description	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.
Arm/Group Title	Optivate 500IU
Arm/Group Description	Optivate 500IU Optivate 500IU
All Cause Mortality
	Optivate 500IU
	Affected / at Risk (%)	# Events
Total	1/7 (14.3%)
Serious Adverse Events
	Optivate 500IU
	Affected / at Risk (%)	# Events
Total	2/7 (28.6%)
Injury, poisoning and procedural complications
Fatal road traffic accident	1/7 (14.3%)	1
Respiratory, thoracic and mediastinal disorders
Asthmatic crisis	1/7 (14.3%)	1
Other (Not Including Serious) Adverse Events
	Optivate 500IU
	Affected / at Risk (%)	# Events
Total	3/7 (42.9%)
Blood and lymphatic system disorders
ANEMIA	1/7 (14.3%)	1
General disorders
GENERAL PAIN	1/7 (14.3%)	1
Infections and infestations
COMMON COLD	1/7 (14.3%)	1
Injury, poisoning and procedural complications
ANKLE TRAUMA	1/7 (14.3%)	1
SOFT TISSUE TRAUMA LEFT HAND	1/7 (14.3%)	1
Musculoskeletal and connective tissue disorders
HEMARTHROSIS OF RIGHT ELBOW	1/7 (14.3%)	1
JOINT PAIN	1/7 (14.3%)	1
HEMARTHROSIS OF RIGHT KNEE	1/7 (14.3%)	1
Respiratory, thoracic and mediastinal disorders
BRONCHOSPASM	1/7 (14.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.