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: 8

Duration: 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the best way to treat children with hemophilia A, a condition where blood doesn’t clot properly, particularly in those who have developed inhibitors (antibodies that stop treatment from working). Researchers aim to determine if using emicizumab (a humanized bispecific antibody) alone is as effective as combining it with another treatment, FVIII, for maintaining tolerance (the body's acceptance of the treatment). Children with hemophilia A and inhibitors who have successfully completed a specific treatment process are suitable candidates for this trial. Participants will receive either emicizumab alone or with FVIII and will be monitored for up to two years. As a Phase 4 trial, this study involves an FDA-approved treatment and seeks to understand how it can benefit more patients.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop your current medications. However, you must be on emicizumab or willing to switch to it as part of the study.

What is the safety track record for these treatments?

Research has shown that emicizumab is generally safe for people with hemophilia A. Long-term use of emicizumab has been well tolerated, with no reports of serious blood clotting problems. This is crucial because people with hemophilia A can experience bleeding issues.

For those considering both emicizumab and FVIII (factor VIII), direct safety information is limited, but emicizumab alone has a strong safety record. Factor VIII is already approved for treating hemophilia A, so its use is well understood.

Overall, evidence suggests that emicizumab is safe for most patients. However, discussing any concerns with a healthcare provider before joining a trial is always important. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for Hemophilia A because they combine emicizumab with Factor VIII (FVIII) in a novel way. Emicizumab stands out because it mimics the function of FVIII, which is deficient in Hemophilia A patients, but it does so without being FVIII itself, offering a new mechanism of action. The combination of emicizumab with weekly FVIII doses can potentially enhance bleeding prevention more effectively than current standard treatments like FVIII concentrates alone. This innovative approach may offer more stable protection against bleeding episodes, which is a significant improvement over traditional therapies.

What evidence suggests that this trial's treatments could be effective for hemophilia A?

Studies have shown that emicizumab works very well for people with hemophilia A, whether or not they have inhibitors. It greatly reduces bleeding episodes, and some patients don't experience any bleeds at all. This marks a significant improvement over traditional treatments. In this trial, participants will receive either emicizumab alone or in combination with FVIII. When combined with FVIII, emicizumab remains effective, significantly reducing yearly bleeding rates compared to FVIII alone. These findings suggest that emicizumab, with or without additional FVIII, provides strong protection against bleeds for those with hemophilia A. ^{1 3 6 7 8}

Who Is on the Research Team?

Guy Young, MD

Principal Investigator

Professor of Pediatrics, Director of Hemostasis and Thrombosis Center

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either emicizumab plus weekly FVIII or emicizumab alone for prophylaxis

2 years

Monthly visits for the first 4 months, then every 2 months until the first year, at 18 months, and at the end of the study

Follow-up

Participants are monitored for inhibitor recurrence and safety

2 years

Monthly visits for the first 4 months, then every 2 months until the first year, at 18 months, and at the end of the study

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. hemlibra-hcp.com hemlibra-hcp.com/efficacy/clinical-trial-results.html

Clinical Trials | HEMLIBRA® (emicizumab-kxwh) Learn how HEMLIBRA® (emicizumab-kxwh) was studied in hemophilia A patients with and without factor VIII inhibitors in our clinical trials.

2. hemlibra.com hemlibra.com/about/clinical-trial-results.html

HEMLIBRA® (emicizumab-kxwh) Clinical Trial Results View study results and discover how HEMLIBRA® (emicizumab-kxwh) may help people with hemophilia A with or without factor VIII inhibitors.

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1703068

Emicizumab Prophylaxis in Hemophilia A with Inhibitors Emicizumab prophylaxis was associated with a significantly lower rate of bleeding events than no prophylaxis among participants with hemophilia A with ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11063855/

Emicizumab: the hemophilia A game-changer - PMC Results from clinical trials and real-world data are encouraging, showing efficacy and achievement of zero bleeds in a substantial proportion of patients. Hence ...

5. icer.org icer.org/wp-content/uploads/2020/10/ICER_Hemophilia_Final_Evidence_Report_041618.pdf

Emicizumab for Hemophilia A with Inhibitors: Effectiveness ... • Long-term outcomes were not measured in the trials of emicizumab. It is possible that reducing bleeding events will also reduce joint ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5728143/

Long-term safety and efficacy of emicizumab in a phase 1/2 ... Key Points. Long-term, once-weekly emicizumab was well tolerated with no thromboembolic adverse events in patients with hemophilia A.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03020160

NCT03020160 | A Study to Evaluate the Efficacy, Safety, ... This multicenter, open-label, non-randomized study will assess the efficacy, safety, pharmacokinetics, and pharmacodynamics of emicizumab administered at a ...

8. haematologica.org haematologica.org/article/view/haematol.2022.282099

Emicizumab: the hemophilia A game-changer One infant experienced major bleeding after circumcision while on emicizumab, and this episode was associated with suboptimal levels of thrombin ...