Emicizumab for Hemophilia A

(AHAEmi Trial)

Recruiting at 16 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

51 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a phase II multicenter open-label, single-arm prospective study to evaluate the efficacy of prophylactic emicizumab administered on a scheduled basis to prevent bleeds in patients with acquired hemophilia A (AHA).

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.

What data supports the effectiveness of the drug Emicizumab for Hemophilia A?

Research shows that Emicizumab is effective in restoring hemostasis (the process to stop bleeding) in patients with Hemophilia A by mimicking the function of a missing protein, leading to improved outcomes in both those with and without inhibitors. ^{1 2 3 4 5}

Is emicizumab safe for humans?

Emicizumab has been shown to be safe in humans, with its safety proven in multiple trials, including long-term studies lasting up to 5.8 years in patients with severe hemophilia A. ^{1 3 5 6 7}

How is the drug Emicizumab unique for treating Hemophilia A?

Emicizumab is unique because it is a bispecific antibody that mimics the function of missing factor VIII by bridging activated factor IX and factor X, helping to prevent bleeding in Hemophilia A patients. Unlike traditional treatments, it can be administered subcutaneously (under the skin) and is effective for patients with or without factor VIII inhibitors. ^{1 5 8 9 10}

Research Team

Rebecca Kruse-Jarres, MD, MPH

Principal Investigator

University of Washington

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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 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 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, 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]

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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Emicizumab Prophylaxis in Patients Who Have Hemophilia A without Inhibitors. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Safety evaluation of emicizumab prophylaxis in individuals with haemophilia A. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Emicizumab prophylaxis among infants and toddlers with severe hemophilia A and inhibitors-a single-center cohort. [2020]

4. United States 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). [2023]

5. England 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. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Emicizumab prophylaxis in haemophilia patients older than 50 years with cardiovascular risk factors: Real-world data. [2021]

7. England 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. [2021]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Emicizumab-kxwh: First Global Approval. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Detailed analysis of anti-emicizumab antibody decreasing drug efficacy, using plasma samples from a patient with hemophilia A. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Real-world use of emicizumab in patients with haemophilia A: Bleeding outcomes and surgical procedures. [2021]