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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares two standard treatments for people with Hemophilia A, a condition where blood doesn't clot properly due to low levels of a protein called factor VIII. Participants will be randomly assigned to receive either an extended half-life factor VIII treatment (such as Adynovate or Eloctate) or a non-factor treatment called emicizumab. The goal is to determine which treatment works better or has fewer side effects. People with moderate to severe Hemophilia A who are already on or have not started preventive treatment might be a good fit for this trial. As a Phase 4 trial, the treatments are already FDA-approved and proven effective, and this research helps understand how they benefit more patients.

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 is the safety track record for these treatments?

Research shows that the treatments in this trial—Adynovate, Eloctate, and Emicizumab—are generally safe for people with Hemophilia A.

Studies involving 365 patients indicate that Adynovate is well-tolerated. Some individuals might experience mild reactions like headaches or nausea, but these are uncommon.

Eloctate has also been studied in people with Hemophilia A, and its safety aligns with similar treatments. The most common mild side effects include headaches and joint pain.

Emicizumab has been used for over ten years, with safety data from this period. The most common mild side effects are reactions at the injection site, such as redness or itching. Serious effects are rare.

All these treatments have a strong safety record for people with Hemophilia A. If side effects occur, they are usually mild and manageable. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for Hemophilia A because they offer unique approaches to managing the condition. Adynovate and Eloctate are extended half-life factor VIII therapies, meaning they stay in the bloodstream longer than standard treatments, potentially reducing the frequency of infusions needed. Emicizumab, on the other hand, is a non-factor product that works by mimicking the activity of factor VIII without being a factor VIII protein itself. This can be particularly beneficial for patients with inhibitors against factor VIII, offering an alternative pathway to manage bleeding. Overall, these treatments aim to improve convenience and effectiveness for those living with Hemophilia A.

What is the effectiveness track record for these treatments for Hemophilia A?

Research has shown that both Adynovate and Eloctate, part of the extended half-life factor VIII-based replacement therapy arm in this trial, effectively reduce bleeding episodes in people with Hemophilia A. Adynovate helps prevent bleeding with twice-weekly use, resulting in two or fewer bleeds per year. Similarly, Eloctate improves joint health and lowers the risk of bleeding, offering long-term benefits for patients. Another treatment option in this trial, Emicizumab, part of the non-factor VIII-based replacement therapy arm, has significantly reduced bleeding events, with some patients experiencing no bleeds at all. These treatments are well-established and effective options for managing Hemophilia A. ^{5 6 7 8 9}

Who Is on the Research Team?

Jessica Garcia, MD

Principal Investigator

University of Texas Southwestern Medical Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

Citations

1. adynovatepro.com adynovatepro.com/prophylaxis

Prophylaxis Data - ADYNOVATE® In clinical trials, ADYNOVATE demonstrated the ability to help prevent bleeding episodes using a prophylaxis regimen.

2. adynovate.com adynovate.com/prophylaxis

ADYNOVATE® Prophylaxis Treatment. In these ADYNOVATE clinical studies, patients receiving twice-weekly prophylaxis, ADYNOVATE demonstrated 2 bleeds or less per year in children and adults.†. † ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02078427

NCT02078427 | ADVATE/ ADYNOVI Hemophilia A ... The purpose of the study is to document the natural history of hemophilia A disease and long-term outcomes in terms of effectiveness, safety and quality of ...

4. fda.gov fda.gov/media/123626/download

Adynovate 2019 Safety and Utilization Review Efficacy and safety of pegylated full- length recombinant factor VIII with extended half- life for perioperative haemostasis in hemophilia A patients.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10391132/

A Real-World Analysis of Commonly Prescribed FVIII ... Patients with hemophilia A are commonly treated with replacement recombinant factor VIII (rFVIII) products, which can be standard-acting or long-acting.

6. adynovate.com adynovate.com/safety-information

ADYNOVATE®: Safety Information. ADYNOVATE safety has been evaluated in 7 clinical studies in children and adults with severe hemophilia A.1. Understanding inhibitors. Your body may form ...

7. adynovatepro.com adynovatepro.com/safety-profile

Safety Profile - ADYNOVATE® The safety of ADYNOVATE was evaluated in patients (children and adults) (N=365) with severe hemophilia A who received at least 1 dose of ADYNOVATE in 6 ...

8. fda.gov fda.gov/media/94470/download

Package Insert - ADYNOVATE The pooled safety database described in this section reflects exposure of ADYNOVATE in 478 previously treated patients (PTPs) and previously untreated patients ...

9. adynovate.com adynovate.com/

ADYNOVATE®: Hemophilia A Treatment Do not use ADYNOVATE if you: Are allergic to mice or hamster protein; Are allergic to any ingredients in ADYNOVATE or ADVATE [Antihemophilic Factor (Recombinant)].