Alphanate in Immune Tolerance Induction Therapy
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|ClinicalTrials.gov Identifier: NCT03095287|
Recruitment Status : Recruiting
First Posted : March 29, 2017
Last Update Posted : March 30, 2020
This is a multicenter, multinational, prospective, single-arm, nonrandomized, open-label study of approximately 25 male subjects with congenital hemophilia A who will receive their first (primary) immune tolerance induction (ITI) treatment with Alphanate.
The study consists of 2 phases:
- An ITI Treatment Phase in which all eligible subjects will receive ITI treatment with Alphanate for a period of up to 33 months. Upon confirmation of complete immune tolerization, subjects will then enter a 12-month Prophylactic Phase. If, after 33 months of ITI, a subject has achieved partial immune tolerance, the subject will enter a 12-month Prophylactic Phase.
- A 12-month Prophylactic Phase for all subjects who meet the criteria for complete or partial success to continue on a prophylactic dosing regimen of Alphanate.
|Condition or disease||Intervention/treatment||Phase|
|Hemophilia A, Congenital||Biological: Alphanate||Phase 2|
Male subjects <12 years of age presenting with an inhibitor titer >0.6 to <10 Bethesda Units (BU) will be screened before the planned start of ITI treatment. Subjects continuing to meet the entrance criteria will enter the ITI Treatment Phase and receive daily doses of Alphanate 100 IU/kg/day for up to 33 months, with a one-time option to increase to a dosing regimen of 200 IU/kg/day at any time after 90 days of ITI treatment.
Subjects will continue to receive their daily Alphanate dose for up to 33 months until the titer is negative (<0.6 BU) on 2 consecutive assessments and treatment success is confirmed by FVIII:C pharmacokinetic assessments, at which time they will enter the 12 month Prophylactic Phase.
In addition, subjects who have achieved partial immune tolerance at the completion of 33 months of ITI treatment will enter the 12-month Prophylactic Phase. Subjects who do not achieve partial immune tolerance at the completion of 33 months of ITI treatment will be discontinued as treatment failures.
The Prophylactic Phase begins with an 8 week taper period for subjects tolerized with 100 IU/kg/day or with a 12-week taper period for subjects tolerized with 200 IU/kg/day to bring the dose down in a step-wise manner to a prophylactic dose of Alphanate 50 IU/kg every other day or 3 times per week, at the investigator's discretion. During the Prophylactic Phase, subjects will be monitored monthly for the first 4 months and then every 2 months for the remaining 8 months to assess sustainability of immune tolerance.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||25 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Multicenter Phase 2 Open-Label, Single-Arm, Prospective, Interventional Study of Plasma-Derived Factor VIII/VWF (Alphanate®) in Immune Tolerance Induction Therapy in Subjects With Congenital Hemophilia A|
|Actual Study Start Date :||January 3, 2018|
|Estimated Primary Completion Date :||October 2021|
|Estimated Study Completion Date :||October 2022|
Daily intravenous infusion of Alphanate 100 IU/kg/day
Daily intravenous infusion of Alphanate 100 IU/kg/day
Other Name: Factor VIII/von Willebrand Factor
- Complete immune tolerance [ Time Frame: Up to 33 months of treatment ]Proportion of subjects achieving complete immune tolerance within 33 months of initiation of ITI treatment. Complete immune tolerance is defined as achieving undetectable inhibitor, FVIII:C plasma recovery of at least 66% of the predicted normal value, and FVIII-C half-life of at least 6 hours.
- Complete or partial immune tolerance [ Time Frame: Up to 33 months of treatment ]Proportion of subjects who achieve either complete or partial immune tolerance within 33 months of initiation of ITI. Partial immune tolerance is defined as achieving inhibitor level <5 BU or FVIII:C plasma recovery <66% of the predicted normal value or FVIII:C half-life of <6 hours and having a clinical response to FVIII therapy.
- Complete or partial immune tolerance without relapse [ Time Frame: Up to 12 months ]Proportion of subjects who maintain complete immune tolerance or partial immune tolerance without relapse during the Prophylactic Phase. For subjects who have achieved complete immune tolerance, relapse is defined as a return of FVIII inhibitor titer to detectable levels or FVIII:C recovery <66% of the predicted normal value or FVIII:C half-life <6 hours. For subjects who have achieved partial immune tolerance, relapse is defined as an increase of FVIII inhibitor titer to at least 5 BU.
- Frequency of bleeding events [ Time Frame: Up to 45 months ]Annualized frequencies of bleeding events during the ITI Treatment Phase and the Prophylactic Phase
- Treatment-emergent adverse events [ Time Frame: Up to 45 months ]Incidence of treatment-emergent adverse events during the ITI Treatment Phase and Prophylactic Phase
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03095287
|Contact: Donna Babiar||+1 email@example.com|
|Contact: Michael Woodward||+34 firstname.lastname@example.org|