Emicizumab for Hemophilia A

(Beyond ABR Trial)

Recruiting at 54 trial locations

Overseen By Reference Study ID Number: MO42623 https://forpatients.roche.com/

Age: Any Age

Sex: Any

Trial Phase: Phase 4

Sponsor: Hoffmann-La Roche

Must be taking: FVIII prophylaxis

Must not be taking: Investigational drugs

Disqualifiers: Other bleeding disorders, Joint procedures, Osteoarthritis, Cardiovascular disease, 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: 36 months

136 Participants Needed

Trial Summary

What is the purpose of this trial?

Study MO42623 is a Phase IV, multicenter, open-label, three cohort study designed to evaluate the impact of emicizumab prophylaxis on overall health, physical activity, and joint outcomes in participants aged ≥13 and \<70 years with severe hemophilia A without factor VIII (FVIII) inhibitors or moderate hemophilia A without FVIII inhibitors who are receiving FVIII prophylaxis and who will start emicizumab treatment as part of this study.

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 must have been on standard FVIII prophylaxis for at least the last 24 weeks to participate.

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

Research shows that Emicizumab is effective in improving blood clotting in people with Hemophilia A by mimicking the function of a missing protein, leading to better 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 clinical trials for patients with hemophilia A, including those with and without inhibitors. Long-term studies have also supported its safety over several years of use. ^{1 2 4 6 7}

How is the drug Emicizumab different from other treatments for Hemophilia A?

Emicizumab is unique because it is a bispecific antibody that mimics the function of a missing protein (factor VIII) by connecting two other proteins (factor IX and factor X) to help blood clot, and it is given as a subcutaneous injection (under the skin) rather than intravenously (into a vein) like many other treatments. ^{1 2 8 9 10}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for individuals aged 13-69 with severe or moderate Hemophilia A without Factor VIII inhibitors. They must have no history of FVIII inhibitory antibodies in the last 5 years, adequate organ function, and agree to use contraception if applicable. Excluded are those planning major joint procedures, with uncontrolled diseases like cardiovascular issues or HIV not managed by medication, or who've had certain treatments that might interfere with the study.

Inclusion Criteria

My blood, liver, and kidney functions are all within normal ranges.

For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception during the treatment period and for at least 24 weeks after the final dose of emicizumab

I have severe or moderate hemophilia A and was on prophylaxis if moderate.

Exclusion Criteria

Pregnant or breastfeeding, or intending to become pregnant during the study

My HIV is not controlled by medication.

I have a bleeding disorder but not severe or moderate hemophilia A without previous long-term treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants start emicizumab prophylaxis to evaluate its impact on overall health, physical activity, and joint outcomes

36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• Emicizumab

Trial Overview The trial is testing Emicizumab prophylaxis on overall health, physical activity, and joint outcomes in participants. It's an open-label Phase IV study where all participants receive Emicizumab to see how it affects their condition compared to previous standard treatments they were receiving.

Participant Groups

Group I: Cohort 3, Hemophilia A and with Osteochondral Damage: Emicizumab Experimental Treatment 1 Intervention

Cohort 3 comprises participants with severe or moderate hemophilia A and with osteochondral damage (HEAD-US bone and cartilage score of ≥1) in at least one index joint and with any synovitis score.

Group II: Cohort 2, Hemophilia A and with Synovitis Only: Emicizumab Experimental Treatment 1 Intervention

Cohort 2 comprises participants with severe or moderate hemophilia A and with synovitis (HEAD-US synovitis score of ≥1) in at least one index joint and no osteochondral damage (HEAD-US bone and cartilage score of 0).

Group III: Cohort 1, Hemophilia A and Without Arthropathy: Emicizumab Experimental Treatment 1 Intervention

Cohort 1 comprises participants with severe or moderate hemophilia A and with no synovitis and no osteochondral damage (Haemophilia Early Arthropathy Detection with Ultrasound \[HEAD-US\] score of 0) in all index joints.

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

Findings from Research

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 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]

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]

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]

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]

References

1. 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]

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

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

3. England pubmed.ncbi.nlm.nih.gov

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

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

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

5. 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]

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. 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]

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

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

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

Emicizumab-kxwh: First Global Approval. [2019]