FVIII + Emicizumab for Hemophilia A

(PRIORITY Trial)

Age: < 18

Sex: Male

Trial Phase: Phase 4

Sponsor: Children's Hospital Los Angeles

Must be taking: Emicizumab

Disqualifiers: Age >12, Partial tolerance, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

52 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Research Team

Guy Young, MD

Principal Investigator

Professor of Pediatrics, Director of Hemostasis and Thrombosis Center

Eligibility Criteria

This trial is for boys aged 12 or younger with severe or moderate hemophilia A who have had a high inhibitor response (>5 BU) but achieved immune tolerance. They must be currently on emicizumab or agree to switch to it, and within one year of successful immune tolerance induction as per ISTH criteria.

Inclusion Criteria

I am 12 years old or younger.

I am a male with severe or moderate hemophilia A.

History of a high titer (>5 BU) inhibitor

Exclusion Criteria

History per the investigator's discretion of non-compliance to prior therapy.

I am older than 12 years.

I do not want to receive IV treatments for clotting.

Treatment Details

Interventions

• Emicizumab
• FVIII

Trial Overview The study tests if continuing weekly FVIII therapy alongside emicizumab is necessary to maintain immune tolerance in children post-successful ITI compared to just using emicizumab alone. It's a randomized, controlled study with two groups followed for up to two years.

Participant Groups

Group I: Emicizumab + FVIII weekly Active Control 2 Interventions

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.

Group II: Emicizumab only Active Control 1 Intervention

Participants will only receive emicizumab prophylaxis.

Emicizumab is already approved in United States, European Union for the following indications:

Approved in United States as Hemlibra for:

• Hemophilia A
• Hemophilia A with inhibitors

Approved in European Union as Hemlibra for:

• Hemophilia A
• Hemophilia A with inhibitors

Who Is Running the Clinical Trial?

Children's Hospital Los Angeles

Lead Sponsor

Trials

257

Recruited

5,075,000+

Grifols Biologicals, LLC

Industry Sponsor

Trials

33

Recruited

9,500+