Preventing Inhibitor Recurrence Indefinitely

NCT04621916 | Unknown Phase 4 FDA Drug

• 1 other identifier: CHLA-20-00189
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hemophilia A; Immune Tolerance

Outcome Measures

Primary Outcomes (1)

• Inhibitor recurrence

  FVIII inhibitor level will be checked on certain time points during the study.

  The goal is to complete all study procedures in 2 years.

Study Arms (2)

Emicizumab + FVIII weekly

ACTIVE COMPARATOR

In addition to emicizumab prophylaxis,participants will receive non-prophylactic exposure to FVIII concentrates through weekly 50 IU/kg ±10% doses - the choice of FVIII concentrate is at the discretion of the PI.

Drug: FVIII; Drug: Emicizumab

Emicizumab only

ACTIVE COMPARATOR

Participants will only receive emicizumab prophylaxis.

Drug: Emicizumab

Interventions

FVIII DRUG

This study will evaluate the inhibitor recurrence with or without ongoing FVIII exposure in patients with hemophilia A on emicizumab prophylaxis after a successful immune tolerance induction.

Emicizumab + FVIII weekly

Emicizumab DRUG

This study will evaluate the inhibitor recurrence with or without ongoing FVIII exposure in patients with hemophilia A on emicizumab prophylaxis after a successful immune tolerance induction.

Emicizumab + FVIII weekly; Emicizumab only

Eligibility Criteria

• Age: 0 Years - 12 Years
• Gender Eligibility Details: Since Hemophilia is a X-linked bleeding disorder occurring mostly in males we expected to mostly enroll male-identified subjects.
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Children's Hospital Los Angeles: lead
• Grifols Biologicals, LLC: collaborator

Study Sites (1)

Childrens Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

MeSH Terms

Conditions

Hemophilia A

Interventions

emicizumab

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Guy Young, MD

  Professor of Pediatrics, Director of Hemostasis and Thrombosis Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, professor

Study Record Dates

• First Submitted: November 3, 2020
• First Posted: November 9, 2020
• Study Start: September 21, 2020
• Primary Completion: September 20, 2024
• Study Completion: April 20, 2025
• Last Updated: October 5, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

US (1)