Emicizumab for Hemophilia A

(HAVEN 7 Trial)

Not currently recruiting at 68 trial locations

Overseen By Reference Study ID Number: MO41787 https://forpatients.roche.com/

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must not be taking: Immunomodulators, Investigational drugs

Disqualifiers: Other bleeding disorders, Severe bleed, HIV, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: 2

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called emicizumab for babies with severe hemophilia A, a condition where blood doesn't clot properly due to low levels of a protein called factor VIII. The goal is to assess how well emicizumab prevents bleeding and its safety for long-term use. Babies under 12 months old, who have had little or no treatment for hemophilia A, might be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering a chance to contribute to a potentially groundbreaking treatment.

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

The trial does not specify if you need to stop taking your current medications. However, you cannot use systemic immunomodulators (medications that affect the immune system) during the study.

Is there any evidence suggesting that emicizumab is likely to be safe for humans?

Research has shown that emicizumab is generally safe for people with hemophilia A. One study found that patients taking emicizumab experienced fewer bleeding episodes than those not taking it. Another study found that long-term use of emicizumab did not cause serious side effects, such as blood clots. These findings suggest that emicizumab is safe for humans, with no major negative effects reported. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Emicizumab is unique because it offers a new mechanism of action for treating Hemophilia A. Unlike traditional treatments that often involve regular infusions of clotting factors, Emicizumab works by mimicking the activity of these factors, bridging the gap between other co-factors to promote blood clotting. This could mean fewer injections and a more stable control of bleeding episodes for patients. Researchers are excited because this approach not only simplifies treatment but also has the potential to improve the quality of life for those living with Hemophilia A.

What evidence suggests that emicizumab might be an effective treatment for hemophilia A?

Studies have shown that emicizumab effectively treats hemophilia A, a condition where blood doesn't clot properly due to low levels of factor VIII. Research indicates that emicizumab reduces bleeding episodes in people with hemophilia A, regardless of resistance to factor VIII. In previous studies, patients using emicizumab experienced significantly fewer bleeding episodes compared to those not using the treatment. These results remained consistent in both short-term and long-term follow-ups, suggesting that emicizumab could be a reliable option for managing severe hemophilia A. ^{6 7 8 9 10}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

This trial is for babies from birth to 12 months with severe Hemophilia A (FVIII level <1%) without inhibitors. They must be previously untreated or minimally treated, weigh at least 3 kg, have no history of FVIII inhibitor or thrombotic disease, and not be infected with HIV or hepatitis. Parents must commit to the study's requirements.

Inclusion Criteria

I have records of all hemophilia treatments I've received since birth.

A negative test for FVIII inhibitor locally assessed during the 2-week screening period

I have not received much or any treatment for my condition.

Exclusion Criteria

History of clinically significant hypersensitivity associated with specific therapies

I do not have any severe bleeding, like a brain bleed.

I have a genetic or acquired condition that increases my risk of blood clots.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive emicizumab at 3 mg/kg every 2 weeks for 52 weeks

52 weeks

Visits every 2 weeks

Long-term Follow-up

Participants continue to receive emicizumab with varying dosages over a 7-year period

7 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Emicizumab

Trial Overview The study tests Emicizumab's effectiveness and safety in preventing bleeding episodes in young children with Hemophilia A. It involves a weekly injection for one year followed by a long-term follow-up period where dosage frequency may vary.

How Is the Trial Designed?

Group I: Emicizumab Experimental Treatment 1 Intervention

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?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Published Research Related to This Trial

Emicizumab significantly shortened the activated partial thromboplastin time (APTT) in patients with severe hemophilia A after the first dose, indicating its effectiveness in improving blood clotting.

The standard one-stage APTT-based FVIII activity assay (sOSA) produced inaccurately high FVIII activity levels when using emicizumab, suggesting it should not be used for monitoring, while modified OSA (mOSA) effectively quantified emicizumab concentration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of emicizumab on APTT, one-stage and chromogenic assays of factor VIII in artificially spiked plasma and in samples from haemophilia A patients with inhibitors. Bowyer, A., Kitchen, S., Maclean, R.[2020]

In a multicenter study of 93 patients with hemophilia A, the annualized bleeding rates significantly decreased from 4.4 (with inhibitors) and 1.6 (without inhibitors) to just 0.4 after starting treatment with emicizumab, indicating its strong efficacy in preventing bleeding.

The study found no serious drug-related adverse events, thrombotic events, or deaths, highlighting the safety of emicizumab, especially in the largest cohort of children under 12 years without inhibitors treated to date.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world use of emicizumab in patients with haemophilia A: Bleeding outcomes and surgical procedures. McCary, I., Guelcher, C., Kuhn, J., et al.[2021]

Emicizumab is an effective treatment for hemophilia A, significantly reducing bleeding events compared to on-demand treatment and traditional factor VIII prophylaxis, making it a valuable alternative for patients.

The safety profile of emicizumab is generally excellent, with only a few reported cases of thrombotic events, indicating it is a well-tolerated option for managing hemophilia A.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety evaluation of emicizumab prophylaxis in individuals with haemophilia A. Wang, CP., Young, G., Thornburg, CD.[2022]

In a phase 3 trial with 152 participants, emicizumab significantly reduced the annualized bleeding rate in hemophilia A patients without factor VIII inhibitors, showing a 96% reduction compared to no prophylaxis.

Emicizumab was well-tolerated, with the most common side effect being low-grade injection-site reactions, and it did not lead to serious complications like thrombotic events or the development of factor VIII inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emicizumab Prophylaxis in Patients Who Have Hemophilia A without Inhibitors. Mahlangu, J., Oldenburg, J., Paz-Priel, I., et al.[2022]

Emicizumab, administered weekly for up to 5.8 years, was found to be safe with most adverse events being mild and unrelated to the treatment, indicating a favorable safety profile for patients with severe hemophilia A.

The treatment significantly reduced annualized bleeding rates (ABRs) and improved patients' perceptions of bleeding severity and their overall quality of life, with most patients reporting improvements in daily life and reduced anxiety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of emicizumab for up to 5.8 years and patients' perceptions of symptoms and daily life: A phase 1/2 study in patients with severe haemophilia A. Shima, M., Nagao, A., Taki, M., et al.[2021]

In the Phase 3b STASEY study involving 195 participants with hemophilia A, emicizumab prophylaxis demonstrated a favorable safety profile, with no new safety signals identified and only 3.6% of participants discontinuing treatment due to adverse events.

Emicizumab significantly reduced bleeding episodes, with 82.6% of participants experiencing zero treated bleeds over a median exposure of 103.1 weeks, indicating its efficacy in restoring hemostasis in patients with FVIII inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of long-term emicizumab prophylaxis in hemophilia A with factor VIII inhibitors: A phase 3b, multicenter, single-arm study (STASEY). Jiménez-Yuste, V., Peyvandi, F., Klamroth, R., et al.[2023]

Emicizumab is safe and effective in preventing bleeding in very young children with hemophilia A, as shown in a study of 11 children with a median age of 26 months followed for 36 weeks, where none experienced spontaneous bleeds.

While emicizumab was sufficient for most patients to maintain hemostasis, caution is advised during surgeries, as some procedures may still require additional treatment to prevent bleeding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emicizumab prophylaxis among infants and toddlers with severe hemophilia A and inhibitors-a single-center cohort. Barg, AA., Avishai, E., Budnik, I., et al.[2020]

Emicizumab-kxwh (Hemlibra®) is a bispecific monoclonal antibody that effectively restores the function of missing activated FVIII in patients with hemophilia A, facilitating better blood clotting.

It is approved in the USA for routine prophylaxis to prevent bleeding episodes in hemophilia A patients with FVIII inhibitors, and is currently undergoing phase 3 trials for those without FVIII inhibitors, indicating its potential broad application in hemophilia treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emicizumab-kxwh: First Global Approval. Scott, LJ., Kim, ES.[2019]

In a case study of an adult hemophilia A patient with FVIII inhibitors, the efficacy of emicizumab decreased due to the development of anti-drug antibodies (ADAs) that neutralized its activity, leading to repeated bleeding events.

The study found that the concentration of emicizumab in the patient's plasma decreased over time, and the presence of ADAs was linked to accelerated clearance of the drug, which ultimately reduced its effectiveness in managing bleeding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detailed analysis of anti-emicizumab antibody decreasing drug efficacy, using plasma samples from a patient with hemophilia A. Kaneda, M., Kawasaki, R., Matsumoto, N., et al.[2023]

In a study of 17 elderly patients with Haemophilia A, emicizumab was found to be well tolerated and significantly reduced the annualized bleeding rate, indicating its efficacy in this population.

No serious adverse events like thrombosis or thrombotic microangiopathy were reported, suggesting that emicizumab is a safe option for elderly patients, even those with cardiovascular risk factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emicizumab prophylaxis in haemophilia patients older than 50 years with cardiovascular risk factors: Real-world data. Misgav, M., Brutman-Barazani, T., Budnik, I., et al.[2021]

Citations

1. 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.

2. 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.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6596376/

Emicizumab for the treatment of haemophilia A Preliminary results, including ABR, efficacy and safety, were consistent with those of the three previous HAVEN studies. In particular, 56% of patients with or ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2475037924000530

Long-term outcomes with emicizumab in hemophilia A ... This HAVEN 3 and 4 study analysis evaluates long-term outcomes of emicizumab prophylaxis in people with HA without FVIII inhibitors at study closure.

5. emicizumabinfo.com emicizumabinfo.com/patient/scientific-data/long-term-data.html

Long-Term Data - Hemlibra® (emicizumab-kxwh) Long-Term Safety and Efficacy of Emicizumab for up to 5.8 Years and Patients' Perceptions of Symptoms and Daily Life: A Phase 1/2 Study in Patients With Severe ...

6. ashpublications.org ashpublications.org/blood/article/124/20/3165/33262/Anti-factor-IXa-X-bispecific-antibody-ACE910

Anti-factor IXa/X bispecific antibody ACE910 prevents joint ... ACE910 is expected to prevent spontaneous bleeds and joint damage in hemophilia A patients even with weekly SC dosing, although appropriate clinical ...

7. nejm.org nejm.org/doi/full/10.1056/NEJMoa1511769

Factor VIII–Mimetic Function of Humanized Bispecific ... Emicizumab (ACE910), a humanized bispecific antibody mimicking the cofactor function of factor VIII, was developed to abate these problems.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6524866/

Emicizumab, A Bispecific Antibody to Factors IX/IXa and X/ ... A Phase III multicenter trial showed that emicizumab prophylaxis was associated with a significantly lower rate of bleeding events than no prophylaxis or ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S1538783622002914

An anti‐factor IXa/factor X bispecific antibody, emicizumab ... Emicizumab, an anti‐FIXa/FX bispecific antibody, significantly reduces bleeding events in congenital hemophilia A (HA) with and without inhibitors.

10. ashpublications.org ashpublications.org/bloodadvances/article-abstract/1/22/1891/15690

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