Trial Outcomes & Findings for INdividualized ITI Based on Fviii(ATE) Protection by VWF (NCT NCT03204539)

NCT ID: NCT03204539

Last Updated: 2020-05-29

Results Overview

This endpoint was chosen because a shorter time to negative inhibitor should decrease monthly break-through bleeding frequency in the early phase of ITI

Recruitment status

TERMINATED

Study phase

PHASE4

Target enrollment

1 participants

Primary outcome timeframe

completion of immune tolerance induction, up to 18 months

Results posted on

2020-05-29

Participant Flow

Only 1 participant enrolled, but did not complete study due to early study termination.

Participant milestones

Participant milestones
Measure	Alternative Treatment Half of the participants will be randomized to blinded individualized lot selection for ITI. Wilate: Wilate® is a high-purity (i.e. 100 IU FVIII/mg total protein) pdVWF/FVIII complex concentrate.Wilate® possesses all the important features asked for in ITI, namely high purity, a very high pathogen safety profile, and an excellent protection of its FVIII by VWF - all achieved through unique, novel, and innovative techniques.	Standard Treatment The other half of the participants will receive random lot selection for ITI. Wilate: Wilate® is a high-purity (i.e. 100 IU FVIII/mg total protein) pdVWF/FVIII complex concentrate.Wilate® possesses all the important features asked for in ITI, namely high purity, a very high pathogen safety profile, and an excellent protection of its FVIII by VWF - all achieved through unique, novel, and innovative techniques.
Overall Study STARTED	0	1
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Alternative Treatment Half of the participants will be randomized to blinded individualized lot selection for ITI. Wilate: Wilate® is a high-purity (i.e. 100 IU FVIII/mg total protein) pdVWF/FVIII complex concentrate.Wilate® possesses all the important features asked for in ITI, namely high purity, a very high pathogen safety profile, and an excellent protection of its FVIII by VWF - all achieved through unique, novel, and innovative techniques.	Standard Treatment The other half of the participants will receive random lot selection for ITI. Wilate: Wilate® is a high-purity (i.e. 100 IU FVIII/mg total protein) pdVWF/FVIII complex concentrate.Wilate® possesses all the important features asked for in ITI, namely high purity, a very high pathogen safety profile, and an excellent protection of its FVIII by VWF - all achieved through unique, novel, and innovative techniques.
Overall Study Loss of funding	0	1

Baseline Characteristics

INdividualized ITI Based on Fviii(ATE) Protection by VWF

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Alternative Treatment Half of the participants will be randomized to blinded individualized lot selection for ITI. Wilate: Wilate® is a high-purity (i.e. 100 IU FVIII/mg total protein) pdVWF/FVIII complex concentrate.Wilate® possesses all the important features asked for in ITI, namely high purity, a very high pathogen safety profile, and an excellent protection of its FVIII by VWF - all achieved through unique, novel, and innovative techniques.	Standard Treatment n=1 Participants The other half of the participants will receive random lot selection for ITI. Wilate: Wilate® is a high-purity (i.e. 100 IU FVIII/mg total protein) pdVWF/FVIII complex concentrate.Wilate® possesses all the important features asked for in ITI, namely high purity, a very high pathogen safety profile, and an excellent protection of its FVIII by VWF - all achieved through unique, novel, and innovative techniques.	Total n=1 Participants Total of all reporting groups
Age, Customized Age	—	5 years n=7 Participants	5 years n=5 Participants
Sex: Female, Male Female	—	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	—	1 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	—	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	—	1 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	—	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	—	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	—	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	—	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	—	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	—	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) More than one race	—	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	—	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	—	1 participants n=7 Participants	1 participants n=5 Participants

PRIMARY outcome

Timeframe: completion of immune tolerance induction, up to 18 months

Population: Study terminated, and no participants completed study. No outcome measure data to report.

This endpoint was chosen because a shorter time to negative inhibitor should decrease monthly break-through bleeding frequency in the early phase of ITI

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: completion of immune tolerance induction, up to 18 months

Population: Study terminated, and no participants completed study. No outcome measure data to report.

Secondary endpoints include time to achieve partial and complete success as defined according to the following criteria: * Inhibitor titer \<0.6 BU. * Incremental in vivo FVIII recovery in the normal range \[≥66% of normal (1.5% per IU/kg), equal to 0.99%per IU/kg\] with samples taken prior to and 15 or 30 minutes after concentrate treatment. The recovery assessment should be done without any wash-out period. * Half-life of FVIII \>6 hours. The half-life assessment should be done in a non-bleeding status without any wash-out period. Complete Success (CS) of ITI: All three criteria above met. Partial Success (PS) of ITI: The first two of the three criteria above met. Partial Response (PR) of ITI: One of the three criteria above met. Partial Failure (PF) of ITI: Inhibitor still present, but titer is decreased to \<5 BU in contrast to ≥5 BU before start. Complete Failure (CF) of ITI: None of the above mentioned criteria met, and the inhibitor titer is still ≥5 BU.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: one year after completion of immune tolerance induction, up to 30 months

Population: Study terminated, and no participants completed study. No outcome measure data to report.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: completion of immune tolerance induction, up to 18 months

Population: Study terminated, and no participants completed study. No outcome measure data to report.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: completion of immune tolerance induction, up to 18 months

Population: Study terminated, and no participants completed study. No outcome measure data to report.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: completion of immune tolerance induction, up to 18 months

Population: Study terminated, and no participants completed study. No outcome measure data to report.

measured with the Haemo-QOL questionnaire

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: completion of immune tolerance induction, up to 18 months

Population: Study terminated, and no participants completed study. No outcome measure data to report.

We will be looking at drug accountability reports/ logs which will reflect each subject's usage of Wilate

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: completion of immune tolerance induction, up to 18 months

Population: Study terminated, and no participants completed study. No outcome measure data to report.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: screening/baseline

Population: Study terminated, and no participants completed study. No outcome measure data to report.

If subject consents, the following assays will be performed: epitope mapping immunogenotyping/HLA genotyping FVIII genetic testing

Outcome measures

Outcome data not reported

Adverse Events

Alternative Treatment

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Standard Treatment

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Alternative Treatment Half of the participants will be randomized to blinded individualized lot selection for ITI. Wilate: Wilate® is a high-purity (i.e. 100 IU FVIII/mg total protein) pdVWF/FVIII complex concentrate.Wilate® possesses all the important features asked for in ITI, namely high purity, a very high pathogen safety profile, and an excellent protection of its FVIII by VWF - all achieved through unique, novel, and innovative techniques.	Standard Treatment n=1 participants at risk The other half of the participants will receive random lot selection for ITI. Wilate: Wilate® is a high-purity (i.e. 100 IU FVIII/mg total protein) pdVWF/FVIII complex concentrate.Wilate® possesses all the important features asked for in ITI, namely high purity, a very high pathogen safety profile, and an excellent protection of its FVIII by VWF - all achieved through unique, novel, and innovative techniques.
Infections and infestations Sepsis	— 0/0 • 6 months Only 1 participant enrolled in study (Standard treatment arm) due to loss of funding.	100.0% 1/1 • Number of events 1 • 6 months Only 1 participant enrolled in study (Standard treatment arm) due to loss of funding.

Other adverse events

Other adverse events
Measure	Alternative Treatment Half of the participants will be randomized to blinded individualized lot selection for ITI. Wilate: Wilate® is a high-purity (i.e. 100 IU FVIII/mg total protein) pdVWF/FVIII complex concentrate.Wilate® possesses all the important features asked for in ITI, namely high purity, a very high pathogen safety profile, and an excellent protection of its FVIII by VWF - all achieved through unique, novel, and innovative techniques.	Standard Treatment n=1 participants at risk The other half of the participants will receive random lot selection for ITI. Wilate: Wilate® is a high-purity (i.e. 100 IU FVIII/mg total protein) pdVWF/FVIII complex concentrate.Wilate® possesses all the important features asked for in ITI, namely high purity, a very high pathogen safety profile, and an excellent protection of its FVIII by VWF - all achieved through unique, novel, and innovative techniques.
Infections and infestations Fever	— 0/0 • 6 months Only 1 participant enrolled in study (Standard treatment arm) due to loss of funding.	100.0% 1/1 • Number of events 1 • 6 months Only 1 participant enrolled in study (Standard treatment arm) due to loss of funding.
General disorders Headache	— 0/0 • 6 months Only 1 participant enrolled in study (Standard treatment arm) due to loss of funding.	100.0% 1/1 • Number of events 1 • 6 months Only 1 participant enrolled in study (Standard treatment arm) due to loss of funding.

Additional Information

Dr. Jonathan Ducore

UC Davis

Phone: 916-734-3461

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place