Novel Replacement Therapies for Hemophilia A

Overseen By Jessica Garcia, MD

Age: < 18

Sex: Any

Trial Phase: Phase 4

Sponsor: Jessica Garcia

Must not be taking: Bisphosphonates, Corticosteroids, Estrogen, others

Disqualifiers: FVIII inhibitor, Target joints, Synovectomy, 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

Compensation: Varies

Number of Visits: 4

Duration: 12 months

28 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a prospective, randomized control trial in which each patient will be randomly assigned to receive either extended half-life factor VIII based replacement therapy or non-FVIII based replacement therapy, which are both standard of care treatment for persons with Hemophilia A.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are using medications that affect bone and mineral metabolism, like corticosteroids or thyroid hormone therapy.

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

Research shows that Efmoroctocog alfa and Emicizumab are effective in treating Hemophilia A. Efmoroctocog alfa has an extended half-life, making it effective for bleeding prevention, while Emicizumab helps restore blood clotting by mimicking a missing protein function. ^{1 2 3 4 5}

Is the treatment generally safe for humans?

Efmoroctocog alfa and Emicizumab have been studied in clinical trials for hemophilia A and are generally well tolerated. Efmoroctocog alfa showed some occurrence of inhibitors (immune responses) in about one-third of previously untreated patients, while Emicizumab has been used safely in patients with and without inhibitors. ^{1 2 5 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 missing factor VIII, allowing it to be administered subcutaneously (under the skin) once a week, unlike traditional treatments that require frequent intravenous infusions. This makes it more convenient and less burdensome for patients, especially those with inhibitors. ^{2 3 4 8 9}

Research Team

Jessica Garcia, MD

Principal Investigator

University of Texas Southwestern Medical Center

Eligibility Criteria

This trial is for young individuals under 18 with moderate to severe Hemophilia A, either on standard treatments or not yet treated. It's not for those with FVIII inhibitors, a history of joint surgery (synovectomy), more than one target joint, or conditions affecting bone health.

Inclusion Criteria

I have moderate or severe hemophilia A and may or may not be on standard treatment.

I am under 18 years old.

Exclusion Criteria

I have had issues with two or more specific joints.

I do not have conditions like hyperparathyroidism or Paget's disease that affect bone health.

Subjects with documented FVIII inhibitor

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either extended half-life factor VIII based replacement therapy or non-FVIII based replacement therapy

12 months

4 visits (in-person) at baseline, 1 month, 6 months, and 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Adynovate
• Eloctate
• Emicizumab

Trial Overview The study compares two types of Hemophilia A treatments: extended half-life factor VIII replacement therapy and non-FVIII based therapy. Patients are randomly chosen to receive one of these standard care options.

Participant Groups

Group I: Extended half-life factor VIII-based replacement therapy Active Control 2 Interventions

Subjects who are either already on prophylactic standard half-life FVIII products or have not started prophylactic treatment will be randomized to start prophylactic extended half-life FVIII products or non-factor product (emicizumab). Both therapies are considered the current standard of care. The study has 4 planned visits at baseline, 1 month, 6 months, and 12 months. They will coincide with the standard of care visits.

Group II: Non-Factor VIII-based replacement therapy Active Control 1 Intervention

Subjects who are either already on prophylactic standard half-life FVIII products or have not started prophylactic treatment will be randomized to start prophylactic extended half-life FVIII products or non-factor product (emicizumab). Both therapies are considered the current standard of care. The study has 4 planned visits at baseline, 1 month, 6 months, and 12 months. They will coincide with the standard of care visits.

Adynovate is already approved in United States for the following indications:

Approved in United States as Adynovate for:

• Hemophilia A

Who Is Running the Clinical Trial?

Jessica Garcia

Lead Sponsor

Trials

1

Recruited

30+

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Findings from Research

Efmoroctocog alfa (Elocta) is a recombinant factor VIII-Fc fusion protein that has a longer half-life than traditional factor VIII treatments, making it effective for managing bleeding in patients with severe hemophilia A, as shown in pivotal phase III studies involving adults, adolescents, and children.

Patients using efmoroctocog alfa for prophylaxis experienced a significant reduction in injection frequency compared to previous treatments, which may enhance treatment adherence without increasing the risk of immunogenicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efmoroctocog Alfa: A Review in Haemophilia A. Frampton, JE.[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]

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]

A study of 774 patients with hemophilia A revealed that the most common dosing frequency for both efmoroctocog alfa and rurioctocog alfa pegol was twice weekly, indicating a standard treatment regimen for these extended half-life factor VIII products.

Patients using efmoroctocog alfa had a higher mean weekly consumption of 105.4 IU/kg compared to 96.8 IU/kg for rurioctocog alfa pegol, suggesting that while both treatments are effective, there may be differences in dosing requirements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Real-World Dose and Consumption for Two Extended Half-Life Recombinant Factor VIII Products for the Treatment of Hemophilia A in the United States. Wu, Y., Sun, SX., Fan, T.[2022]

In a phase 3 trial involving 109 male participants with hemophilia A and factor VIII inhibitors, emicizumab prophylaxis significantly reduced annualized bleeding rates by 87% compared to no prophylaxis, with a rate of 2.9 events versus 23.3 events (P<0.001).

Emicizumab also demonstrated a 79% reduction in bleeding rates compared to previous bypassing-agent prophylaxis in participants who had received it, indicating its efficacy as a preventive treatment for bleeding in hemophilia A.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emicizumab Prophylaxis in Hemophilia A with Inhibitors. Oldenburg, J., Mahlangu, JN., Kim, B., et al.[2022]

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]

Efmoroctocog alfa (Elocta®) is an effective extended half-life recombinant factor VIII treatment for patients with severe hemophilia A, showing similar or reduced bleeding rates compared to standard half-life products while requiring fewer injections.

In clinical practice, efmoroctocog alfa has been well tolerated, although approximately one-third of previously untreated patients developed inhibitors, indicating a need for monitoring in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efmoroctocog Alfa: A Review in Haemophilia A. Frampton, JE.[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, a bispecific antibody designed to mimic the function of FVIIIa, significantly reduces annual bleeding rates in patients with hemophilia A, even in those with inhibitors, and allows for once-weekly subcutaneous administration, improving patient quality of life.

While emicizumab has shown promising efficacy, there were reports of thrombotic complications in some patients when used with activated prothrombin complex concentrates, highlighting the need for further safety studies and monitoring protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Emicizumab, a bispecific antibody mimicking factor VIII: a novel alternative therapy for hemophilia A with inhibitors]. Nogami, K.[2019]

References

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

Efmoroctocog Alfa: A Review in Haemophilia A. [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

Safety and efficacy of long-term emicizumab prophylaxis in hemophilia A with factor VIII inhibitors: A phase 3b, multicenter, single-arm study (STASEY). [2023]

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

Comparison of Real-World Dose and Consumption for Two Extended Half-Life Recombinant Factor VIII Products for the Treatment of Hemophilia A in the United States. [2022]

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

Emicizumab Prophylaxis in Hemophilia A with Inhibitors. [2022]

6. 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]

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

Efmoroctocog Alfa: A Review in Haemophilia A. [2022]

8. England pubmed.ncbi.nlm.nih.gov

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

9. Japan pubmed.ncbi.nlm.nih.gov

[Emicizumab, a bispecific antibody mimicking factor VIII: a novel alternative therapy for hemophilia A with inhibitors]. [2019]