A Multi-center, Prospective Study Evaluating the Rate of Inhibitor Recurrence Following Successful ITI in Patients Receiving Ongoing Once Per Weekly Factor VIII Therapy Along With Emicizumab and in Patients Who Discontinue FVIII Therapy and Are on Emicizumab for Prophylaxis

CHLA-20-00189

This study will enroll children who have hemophilia A with inhibitors who successfully completed immune tolerance induction per the ISTH criteria (negative inhibitor titer, recovery \>66% of expected, and half-life of \>6 hours with their current FVIII concentrate). Previous to emicizumab, there was only one option for these patients which was to continue FVIII therapy in a prophylaxis mode to prevent bleeding. There was a sense that the ongoing FVIII served to maintain tolerance however no evidence for this notion exists and in fact what limited data is available suggests that continuing FVIII may not be necessary simply to maintain tolerance. To figure out this question, this will be a randomized, controlled 2 arm study which will randomize patients post-successful ITI to emicizumab plus weekly FVIII (for maintenance of tolerance) versus emicizumab alone. Patients will be followed for up to 2 years. We aim to enroll 52 subjects. The FVIII weekly arm can use any factor VIII concentrate and emicizumab is standard of care for inhibitor and non-inhibitor patients.

2020-09-21

2024-09-20

2025-04-20

Active (not recruiting)

Early phase I

52

Inclusion Criteria: * Age ≤12 years at the time of signing the informed consent * Male patients with severe (\<1%) or moderate (\<2%) hemophilia A * History of a high titer (\>5 BU) inhibitor * Within 1 year of successful ITI, according to ISTH definitions (inhibitor titer \<0.6 BU, recovery more than 60% of expected, and half-life of \>6 hours). Successful ITI has been achieved with any FVIII concentrate. * Currently on emicizumab or willing to alter their prophylaxis treatment to emicizumab per study protocol. Exclusion Criteria: * Age \>12 years at the time of signing the informed consent * Partial tolerance (not meeting criteria for complete tolerance per ISTH) * History of anti-drug antibodies to emicizumab * Unwilling to receive exposure to intravenous FVIII concentrates. * History per the investigator's discretion of non-compliance to prior therapy.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE4'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'PREVENTION', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 52, 'type': 'ESTIMATED'}}

2023-10-05