Trial Outcomes & Findings for Alphanate in Immune Tolerance Induction Therapy (NCT NCT03095287)

NCT ID: NCT03095287

Last Updated: 2021-11-23

Results Overview

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

2 participants

Primary outcome timeframe

Up to 32.5 months

Results posted on

2021-11-23

Participant Flow

Participants took part in the study at two sites in India from 03 January 2018 (first participant enrolled to receive the study drug) to 18 September 2020 (last participant completed).

Male participants with diagnosis of Congenital Hemophilia A were enrolled in a single arm to receive alphanate. The study was to be conducted in 2 phases: Immune Tolerance Induction Phase followed by Prophylactic Phase. However, due to the limited enrollment, the study was terminated prior to the start of Prophylactic Phase.

Participant milestones

Participant milestones
Measure	Alphanate Participants entered the immune tolerance induction (ITI) phase and received alphanate IV at a starting dose of 100 IU/kg/day. Dose could be uptitrated to 200 IU/kg/day based on investigator's discretion. The maximum duration of treatment was 32 months and 2 weeks.
Overall Study STARTED	2
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Alphanate Participants entered the immune tolerance induction (ITI) phase and received alphanate IV at a starting dose of 100 IU/kg/day. Dose could be uptitrated to 200 IU/kg/day based on investigator's discretion. The maximum duration of treatment was 32 months and 2 weeks.
Overall Study Treatment Failure	1
Overall Study Adverse Event	1

Baseline Characteristics

Alphanate in Immune Tolerance Induction Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Alphanate n=2 Participants Participants entered the immune tolerance induction (ITI) phase and received alphanate IV at a starting dose of 100 IU/kg/day. Dose could be uptitrated to 200 IU/kg/day based on investigator's discretion. The maximum duration of treatment was 32 months and 2 weeks.
Age, Categorical <=18 years	2 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 32.5 months

Population: Data for this outcome measure was not collected and analysed, as the study was early terminated by the sponsor due to limited enrollment (non-safety related decision).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 32.5 months

Population: Data for this outcome measure was not collected and analysed, as the study was early terminated by the sponsor due to limited enrollment (non-safety related decision).

Complete immune tolerance was defined as the participants achieving 2 consecutive undetectable inhibitor titers (\<0.6 BU) performed within 2 weeks of each other, Factor VIII activity (FVIII:C) in vivo plasma recovery ≥66% of the predicted normal value and FVIII:C half-life ≥6 hours after a 72-hour FVIII treatment-free period. Partial immune tolerance was defined as participants achieving reduction of inhibitor titer to \<5 BU confirmed at 2 consecutive assessments within 2 weeks of each other, FVIII:C in vivo plasma recovery of \<66% of the predicted normal value or FVIII:C half-life of \<6 hours after a 72-hour FVIII treatment-free period and clinical response to FVIII therapy.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 12 months during prophylactic phase

Population: Data for this outcome measure was not collected and analysed, as the study was early terminated by the sponsor due to limited enrollment (non-safety related decision).

Relapse during the prophylactic phase for participants who have achieved complete immune tolerance was defined as a return of FVIII inhibitor titer to detectable levels (≥0.6 BU) or FVIII:C recovery \<66% of the predicted normal value or FVIII:C half-life \<6 hours, confirmed by repeat assessment within approximately 2 weeks. Relapse for participants who have achieved partial immune tolerance was defined as an increase of FVIII inhibitor titer to ≥5 BU, confirmed by repeat assessment within approximately 2 weeks.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 32.5 months

Population: This study was terminated, and the data is not reported for this outcome measure to maintain participant's confidentiality.

Annualized frequencies of bleeding events during the ITI Treatment Phase and the Prophylactic Phase

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 32.5 months

Incidence of treatment-emergent adverse events during the ITI Treatment Phase and Prophylactic Phase

Outcome measures

Outcome data not reported

Adverse Events

Alphanate

Serious events: 2 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Alphanate n=2 participants at risk Participants entered the ITI phase and received alphanate IV at a starting dose of 100 IU/kg/day. Dose could be uptitrated to 200 IU/kg/day based on investigator's discretion. The maximum duration of treatment was 32 months and 2 weeks.
Infections and infestations Lower respiratory tract infection	50.0% 1/2 • From first dose up to 32.5 months Safety population included all participants who received any amount of alphanate.
Injury, poisoning and procedural complications Subdural hemorrhage	50.0% 1/2 • From first dose up to 32.5 months Safety population included all participants who received any amount of alphanate.
Infections and infestations Device related infection	50.0% 1/2 • From first dose up to 32.5 months Safety population included all participants who received any amount of alphanate.
Investigations Hepatitis C Antibody positive	50.0% 1/2 • From first dose up to 32.5 months Safety population included all participants who received any amount of alphanate.

Other adverse events

Other adverse events
Measure	Alphanate n=2 participants at risk Participants entered the ITI phase and received alphanate IV at a starting dose of 100 IU/kg/day. Dose could be uptitrated to 200 IU/kg/day based on investigator's discretion. The maximum duration of treatment was 32 months and 2 weeks.
Vascular disorders Thrombophlebitis	50.0% 1/2 • From first dose up to 32.5 months Safety population included all participants who received any amount of alphanate.
General disorders Pyrexia	100.0% 2/2 • From first dose up to 32.5 months Safety population included all participants who received any amount of alphanate.
Investigations Transaminases increased	50.0% 1/2 • From first dose up to 32.5 months Safety population included all participants who received any amount of alphanate.
Blood and lymphatic system disorders Anaemia	50.0% 1/2 • From first dose up to 32.5 months Safety population included all participants who received any amount of alphanate.
Nervous system disorders Headache	50.0% 1/2 • From first dose up to 32.5 months Safety population included all participants who received any amount of alphanate.
Musculoskeletal and connective tissue disorders Pain in extremity	50.0% 1/2 • From first dose up to 32.5 months Safety population included all participants who received any amount of alphanate.
Musculoskeletal and connective tissue disorders Joint swelling	50.0% 1/2 • From first dose up to 32.5 months Safety population included all participants who received any amount of alphanate.
Injury, poisoning and procedural complications Ligament sprain	50.0% 1/2 • From first dose up to 32.5 months Safety population included all participants who received any amount of alphanate.
Infections and infestations Varicella	50.0% 1/2 • From first dose up to 32.5 months Safety population included all participants who received any amount of alphanate.
Infections and infestations Upper respiratory tract infection	50.0% 1/2 • From first dose up to 32.5 months Safety population included all participants who received any amount of alphanate.
Injury, poisoning and procedural complications Joint injury	50.0% 1/2 • From first dose up to 32.5 months Safety population included all participants who received any amount of alphanate.
Infections and infestations Nasopharyngitis	50.0% 1/2 • From first dose up to 32.5 months Safety population included all participants who received any amount of alphanate.

Additional Information

Rhonda Griffin

Grifols Therapeutics LLC

Phone: 919-316-6693

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Site may publish results from the Study, after providing Sponsor thirty days' notice prior to submitting a manuscript or other materials related to the Study to any outside party. At Sponsors' request, Site will remove any Confidential Information (other than Study results), and Site will upon Sponsors' request, delay publication or presentation for a period of up to one hundred twenty days to allow Sponsor to protect its interests in any Sponsor Inventions.
Publication restrictions are in place

Restriction type: OTHER