Emicizumab for Hemophilia A

(AHAEmi Trial)

Not currently recruiting at 18 trial locations

Overseen By Sarah Ruuska, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Washington

Must be taking: Emicizumab

Must not be taking: aPCC, Investigational drugs

Disqualifiers: Congenital hemophilia A, Lupus anticoagulant, Severe infection, 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

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests emicizumab, a bispecific antibody, to determine its effectiveness in preventing bleeding in individuals with acquired hemophilia A, a condition where blood doesn't clot properly. The goal is to assess how well emicizumab works when administered regularly. Suitable candidates for this trial include those currently experiencing bleeding due to acquired hemophilia A and willing to adhere to a treatment schedule with emicizumab. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have been treated with certain investigational drugs or aPCC recently, and you should not be on current treatment for thromboembolic disease.

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

Research has shown that emicizumab is generally well-tolerated by people with hemophilia A. One study found that most patients experienced fewer bleeding events with emicizumab compared to those without it. Long-term data indicate that emicizumab effectively controls bleeding for up to 5.8 years.

Serious side effects are rare. Common side effects include mild reactions at the injection site and headaches. Long-term studies have not identified any new safety concerns. The FDA has already approved emicizumab for other types of hemophilia A, supporting its safety. Overall, emicizumab appears to be a safe and effective treatment option. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for hemophilia A?

Emicizumab is unique because it works differently than most traditional treatments for Hemophilia A, which often involve factor VIII replacement therapy. Instead of replacing the missing clotting factor, emicizumab acts as a bispecific antibody, bridging factors IXa and X to facilitate blood clotting. This novel mechanism allows for subcutaneous administration, making it more convenient than the frequent intravenous infusions required by standard therapies. Researchers are excited about emicizumab because it has the potential to offer more stable protection against bleeding with fewer disruptions to daily life.

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

Research shows that emicizumab, the treatment under study in this trial, reduces bleeding episodes in people with hemophilia A. Earlier studies demonstrated that emicizumab significantly lowered the number of bleeds, even in patients with inhibitors to factor VIII, proteins crucial for blood clotting. Specifically, data from these studies indicated that up to 56% of patients experienced no bleeding episodes while using this treatment. Emicizumab acts like factor VIII, aiding proper blood clotting. Long-term studies have also shown that its benefits and safety remain consistent over time. ^{1 2 3 6 7}

Who Is on the Research Team?

Rebecca Kruse-Jarres, MD, MPH

Principal Investigator

University of Washington

Are You a Good Fit for This Trial?

Adults diagnosed with acquired Hemophilia A, evidenced by reduced FVIII activity and positive FVIII inhibitor, can join this trial. They must be willing to adhere to emicizumab prophylaxis, not have used certain clotting treatments recently, and women of childbearing age should use effective contraception or abstain from sex.

Inclusion Criteria

Ability to comply with the study protocol, in the investigator's judgment

Plan to be adherent to emicizumab prophylaxis during the study

Signed Informed Consent/Assent Form

Exclusion Criteria

Pregnant or breast-feeding women

Addiction or other diseases that preclude the patient from appropriately assessing the nature and scope as well as possible consequences of the clinical study by the discretion of the investigator

Concurrent disease, treatment, or abnormality in clinical laboratory tests that could interfere with the conduct of the study, may pose additional risk, or would, in the opinion of the local investigator, preclude the patient's safe participation in and completion of the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive emicizumab with two loading doses followed by weekly subcutaneous administration for 12 weeks

12 weeks

Weekly visits (in-person)

Extended Treatment

If partial remission is not achieved, an additional 12 weeks of emicizumab may be given

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including adverse events and mortality

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Emicizumab

Trial Overview The study is testing the effectiveness of emicizumab given regularly to prevent bleeding in patients with acquired Hemophilia A. It's a phase II trial where all participants receive the same treatment without being compared to another group.

How Is the Trial Designed?

Group I: Experimental-treatment Experimental Treatment 1 Intervention

Treatment with emicizumab

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?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

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]

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]

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]

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]

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]

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]

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 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 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]

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. 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 ...

5. 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.

6. gene.com gene.com/media/press-releases/14959/2022-07-11/new-data-from-phase-iii-haven-6-study-re

Genentech: Press Releases | Monday, Jul 11, 2022 Hemlibra continues to demonstrate clinically meaningful bleed control, with 66.7% of participants with moderate or mild hemophilia A experiencing zero treated ...

7. 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 ...