Hemlibra for Mild Hemophilia A

Overseen By Usha Sirimalle, MS

Age: < 65

Sex: Male

Trial Phase: Phase 4

Sponsor: Indiana Hemophilia &Thrombosis Center, Inc.

Must not be taking: Systemic immunomodulators

Disqualifiers: Female, CVD, TMA, HIV, 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

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a single arm, phase 4, prospective, open-label, United States single-center study to determine the hemostatic characteristics of Hemlibra (emicizumab) as measured by coagulation laboratory parameters in the mild hemophilia A male patient population with endogenous altered FVIII (baseline FVIII activity of \>5% to 30%). The safety and hemostatic efficacy of Hemlibra (emicizumab) in this patient population will be investigated. Secondary outcomes will assess changes in joint health and quality of life in treated patients.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are using systemic immunomodulators or certain investigational drugs. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the drug Hemlibra (Emicizumab) for mild 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, factor VIII, which helps blood to clot. It has been shown to improve outcomes in patients with and without inhibitors, suggesting it could be beneficial for those with mild Hemophilia A as well. ^{1 2 3 4 5}

Is Hemlibra (Emicizumab) generally safe for humans?

Emicizumab (Hemlibra) has been studied for its safety in people with hemophilia A, including those with severe cases, over long periods (up to 5.8 years). These studies have shown that it is generally safe for use in humans. ^{1 2 6 7 8}

How is the drug Emicizumab (Hemlibra) different from other treatments for mild Hemophilia A?

Emicizumab (Hemlibra) 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 that require frequent intravenous infusions, Emicizumab is administered subcutaneously (under the skin), making it more convenient for patients. ^{1 6 9 10 11}

Research Team

Amy Shapiro, MD

Principal Investigator

Indiana Hemophilia &Thrombosis Center, Inc.

Eligibility Criteria

This trial is for males aged 5-45 with mild congenital hemophilia A (FVIII level >5% to 30%), without FVIII inhibitors or history of them. Participants must have documented bleeding events and be willing to undergo specific challenges if they've had no prior adverse reactions. Exclusions include previous emicizumab use, other investigational drugs recently, certain cardiovascular risks, additional bleeding disorders, drug/alcohol abuse, and significant hypersensitivity to monoclonal antibodies.

Inclusion Criteria

Diagnosis of mild congenital hemophilia A (baseline FVIII level of >5% to 30%) without a current FVIII inhibitor or a history of FVIII inhibitor

Willingness to undergo a Stimate/DDAVP challenge (only if the subject reports no adverse event associated with prior Stimate [DDAVP/desmopressin acetate] use); Stimate/DDAVP challenge will not be performed if the patient has a documented history of lack of response as defined by an increase of FVIII < 2 times baseline level

Signed informed consent form from the subject, parent or guardian

Exclusion Criteria

Receipt of any of the following: Hemlibra (emicizumab) in a prior investigational study, An investigational drug to treat or reduce the risk of hemophilic bleeds within 5 half-lives of last drug administration, A non-hemophilia-related investigational drug within last 30 days or 5 half-lives, whichever is shorter, Any other investigational drug currently being administered or planned to be administered, Inability to comply with the study protocol in the opinion of the Study Investigator

Use of systemic immunomodulators (eg, interferon) at enrollment or planned use during the study, with the exception of anti-retroviral therapy

Concomitant disease, condition, significant abnormality on screening evaluations or laboratory tests, or treatment that could interfere with the conduct of the study, or that would, in the opinion of the Study Investigator, pose an additional unacceptable risk in administering study drug to the patient

Timeline

Screening

Participants are screened for eligibility to participate in the trial

Up to 4 weeks

1 visit (in-person)

Part A: Loading Dose Administration

Administration of 4 weekly loading doses of Hemlibra (emicizumab) and collection of baseline laboratory data

1 month

4 visits (in-person)

Part A: Maintenance Hemlibra Therapy

Collection of laboratory data and monitoring of bleeding events, quality of life, and joint health

12 months

3 visits (in-person) at months 4, 7, and 13

Part B: Extended Hemlibra Therapy

Continuation of Hemlibra treatment to acquire additional data on bleeding events, quality of life, and joint health

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 35 months

Treatment Details

Interventions

• Emicizumab

Trial Overview The study tests Hemlibra (emicizumab) in a single-arm phase 4 trial focusing on its blood clotting effects in mild hemophilia A patients. It aims to determine safety and effectiveness by monitoring coagulation lab parameters, changes in joint health, and quality of life improvements.

Participant Groups

Group I: Single Arm Experimental Treatment 1 Intervention

Patients with mild hemophilia A (without inhibitors) will be treated with prophylactic emicizumab. The clinical hemostatic efficacy and safety will be assessed. Secondary outcomes will assess changes in quality of life and joint health in treated patients.

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?

Indiana Hemophilia &Thrombosis Center, Inc.

Lead Sponsor

Trials

6

Recruited

690+

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

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, a treatment for hemophilia A, complicates the dosing of Factor VIII concentrates during bleeding emergencies, but regression models can help estimate FVIII activity in patients under this treatment.

Using data from 27 plasma samples, the study developed models that accurately predict FVIII levels, which could be crucial for managing bleeding situations or surgical procedures in patients receiving emicizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regression Analysis to Estimate the Factor VIII Activity of Patients with Hemophilia A Without Inhibitor who Received Emicizumab Therapy. Hatayama, Y., Motokura, T., Hosoda, Y., 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 a humanized bispecific IgG antibody developed over 10 years to treat Hemophilia A by mimicking the cofactor activity of FVIII, addressing the limitations of conventional FVIII treatments.

The antibody has shown clinical benefits in trials since 2012 and is now approved in multiple countries, significantly improving the quality of life for patients with Hemophilia A.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emicizumab, a humanized bispecific antibody to coagulation factors IXa and X with a factor VIIIa-cofactor activity. Kitazawa, T., Shima, M.[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 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, 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 can effectively manage bleeding events in patients with hemophilia A, allowing for minor bleeding and low-risk procedures to be treated without factor replacement therapy.

For major bleeding events and high-risk surgeries, additional factor VIII replacement is necessary, especially in the initial days, while continuing emicizumab treatment throughout the procedure and recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of bleeding events and invasive procedures in patients with haemophilia A without inhibitors treated with emicizumab. Fontana, P., Alberio, L., Albisetti, 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]

Emicizumab, a factor VIII mimetic used for treating Hemophilia A, has a unique mechanism of action that alters the results of standard coagulation tests, necessitating specific laboratory guidelines for monitoring.

The UKHCDO guidelines provide essential recommendations for clinical and laboratory staff on how to accurately measure factor VIII levels and emicizumab itself, ensuring effective treatment and monitoring for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Laboratory coagulation tests and emicizumab treatment A United Kingdom Haemophilia Centre Doctors' Organisation guideline. Jenkins, PV., Bowyer, A., Burgess, C., et al.[2020]

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

Regression Analysis to Estimate the Factor VIII Activity of Patients with Hemophilia A Without Inhibitor who Received Emicizumab Therapy. [2022]

4. England pubmed.ncbi.nlm.nih.gov

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

5. Japan pubmed.ncbi.nlm.nih.gov

Emicizumab, a humanized bispecific antibody to coagulation factors IXa and X with a factor VIIIa-cofactor activity. [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. United States pubmed.ncbi.nlm.nih.gov

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

8. 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]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Management of bleeding events and invasive procedures in patients with haemophilia A without inhibitors treated with emicizumab. [2021]

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

Emicizumab-kxwh: First Global Approval. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Laboratory coagulation tests and emicizumab treatment A United Kingdom Haemophilia Centre Doctors' Organisation guideline. [2020]