Fitusiran for Hemophilia

(ATLAS-OLE Trial)

Not currently recruiting at 247 trial locations

Overseen By Trial Transparency email recommended (Toll free number for US & Canada)

Age: Any Age

Sex: Male

Trial Phase: Phase 3

Sponsor: Genzyme, a Sanofi Company

Must not be taking: Factor concentrates, BPAs

Disqualifiers: Surgery, Liver disease, Thromboembolism, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 48 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines fitusiran, a treatment designed to improve life for individuals with severe hemophilia A or B. It evaluates the long-term safety of fitusiran and its effectiveness in reducing bleeding episodes, including joint bleeds. The trial also assesses whether the treatment enhances participants' quality of life. It is suitable for males aged 12 and older with severe hemophilia who have completed a previous fitusiran Phase 3 trial. As a Phase 3 trial, this study represents the final step before FDA approval, providing participants an opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude those using certain hemophilia treatments like factor concentrates or bypassing agents regularly. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that fitusiran is likely to be safe for humans?

Research has shown that fitusiran appears promising in terms of safety for people with hemophilia. In earlier studies, fitusiran was administered as a monthly shot. The results demonstrated a significant reduction in bleeding episodes compared to standard treatments, suggesting that fitusiran effectively manages bleeding.

One study found that adjusting the target levels of antithrombin, a protein that helps control bleeding, enhanced fitusiran's safety while still preventing bleeding. This adjustment improved fitusiran's safety profile for patients.

Another study examined the long-term safety of fitusiran and found it to be well tolerated. While potential risks exist with any treatment, these studies provide encouraging signs that fitusiran is generally safe for people with hemophilia. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for hemophilia?

Unlike the standard of care for hemophilia, which often involves regular intravenous infusions of clotting factor concentrates, Fitusiran is unique because it is administered as a subcutaneous injection. This treatment offers a new mechanism of action by targeting antithrombin, a protein that normally inhibits blood clotting, to enhance the body’s ability to form clots. Researchers are excited about Fitusiran because it has the potential to simplify treatment regimens with once-monthly or every-other-month dosing, potentially improving patients' quality of life and adherence to therapy.

What evidence suggests that fitusiran might be an effective treatment for hemophilia?

Research has shown that fitusiran reduces bleeding episodes in people with hemophilia A or B. Studies have found that fitusiran lowers antithrombin levels, a protein that controls blood clotting, which then increases thrombin production. This process helps blood clot more normally. Data indicates that people treated with fitusiran experienced fewer bleeds overall, including spontaneous and joint bleeds. Various studies have tested the treatment, showing positive effects on reducing bleeding frequency and potentially improving quality of life for those with hemophilia. Participants in this trial will receive fitusiran as a subcutaneous injection once monthly or every other month. ^{2 6 7 8 9}

Who Is on the Research Team?

Clinical Sciences & Operations

Principal Investigator

Sanofi

Are You a Good Fit for This Trial?

This trial is for males aged 12 or older with severe hemophilia A or B who have finished a Phase 3 fitusiran study. They must be able to consent and follow the study rules. It's not for those on certain other treatments, with liver issues, history of blood clots, recent surgery, or in gene therapy trials.

Inclusion Criteria

I am 12 years old or older.

You have severe hemophilia A or B and have already participated in a Phase 3 clinical trial for fitusiran.

I can sign the consent form and follow the study rules.

Exclusion Criteria

I use treatments other than factor concentrates or BPAs for my hemophilia.

I have a serious liver condition.

I had surgery within the last 14 days or am receiving treatment for bleeding after surgery.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive fitusiran as a subcutaneous injection once monthly or every other month

48 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

42 months

Open-label extension

Participants may continue receiving fitusiran until it becomes commercially available

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Fitusiran

Trial Overview The trial tests the long-term safety and effectiveness of Fitusiran in managing bleeding episodes in hemophilia patients. It looks at how often bleeding occurs and its impact on quality of life over time.

How Is the Trial Designed?

Group I: Fitusiran Experimental Treatment 1 Intervention

Participants will be administered fitusiran as a subcutaneous injection once monthly or every other month for up to 48 months post initiation of modified IMP dose/frequency or until fitusiran becomes commercially available, whichever comes first.

Who Is Running the Clinical Trial?

Genzyme, a Sanofi Company

Lead Sponsor

Trials

528

Recruited

186,000+

David Meeker

Genzyme, a Sanofi Company

Chief Executive Officer since 2011

MD from the University of Vermont Medical School, Advanced Management Program at Harvard Business School

Jean-Paul Kress

Genzyme, a Sanofi Company

Chief Medical Officer since 2015

MD from Faculte Necker-Enfants Malades, Paris

Published Research Related to This Trial

In a phase 3 study involving 120 male participants with severe hemophilia A or B, fitusiran prophylaxis significantly reduced the annualized bleeding rate to 3.1 compared to 31.0 in those receiving on-demand clotting factor concentrates, demonstrating its efficacy in managing bleeding episodes.

Approximately 51% of participants receiving fitusiran had no treated bleeds during the study, indicating a strong potential for fitusiran to transform hemophilia management, with no treatment-related thrombosis or deaths reported, highlighting its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fitusiran prophylaxis in people with severe haemophilia A or haemophilia B without inhibitors (ATLAS-A/B): a multicentre, open-label, randomised, phase 3 trial. Srivastava, A., Rangarajan, S., Kavakli, K., et al.[2023]

Safety surveillance studies are crucial for monitoring the safety of new biological therapies for bleeding disorders, particularly in tracking potential new infectious agents and the development of inhibitors in hemophilia treatment.

The European Haemophilia Safety Surveillance (EUHASS) project aims to establish long-term monitoring of coagulation factor products, addressing challenges like patient recruitment and disease severity assessment through national and international registries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current challenges of pharmacovigilance in bleeding disorders: converting the burden to benefit. Lassila, R., Armstrong, E.[2013]

Fitusiran is an RNA interference therapy that effectively lowers antithrombin levels in patients with hemophilia A and B, leading to improved thrombin generation and reduced bleeding rates, as demonstrated in clinical trials.

While fitusiran is generally well tolerated, caution is advised when used with high doses of clotting factors, as it may increase the risk of thrombosis, highlighting the importance of careful management in patients with severe hemophilia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An investigational RNAi therapeutic targeting antithrombin for the treatment of hemophilia A and B. Machin, N., Ragni, MV.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39642315/

Long-term safety and efficacy of fitusiran prophylaxis, and ... Here, we present the results of a completed phase 2 open-label extension study, which evaluated the long-term safety and efficacy of fitusiran ...

2. ashpublications.org ashpublications.org/bloodadvances/article/9/5/1147/534349/Long-term-safety-and-efficacy-of-fitusiran

Long-term safety and efficacy of fitusiran prophylaxis, and ... The results of this long-term study indicate that fitusiran prophylaxis was effective at reducing AT and restoring sufficient TG to achieve hemostasis and ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0006497125005403

Safety and efficacy of a fitusiran antithrombin-based dose ... Fitusiran lowers AT to increase thrombin generation and restore hemostasis in people with hemophilia A/B with or without inhibitors. •. The AT- ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03549871?intr=fitusiran&rank=6&tab=results

A Study of Fitusiran in Severe Hemophilia A and B Patients ... Study had 2 main periods: 6-month factor/bypassing agent (BPA) prophylaxis period & 7-month fitusiran treatment period (1-month onset and 6-month fitusiran ...

5. sanofi.com sanofi.com/en/media-room/press-releases/2021/2021-12-14-14-00-00-2351761

Data from two Phase 3 studies demonstrating fitusiran ... Data from two Phase 3 studies demonstrating fitusiran significantly reduced bleeds in people with hemophilia A or B, with or without inhibitors ...

6. ashpublications.org ashpublications.org/blood/article/145/25/2966/535965/Safety-and-efficacy-of-a-fitusiran-antithrombin

Safety and efficacy of a fitusiran antithrombin-based dose ... In completed phase 3 trials, once-monthly 80 mg fitusiran prophylaxis significantly reduced annualized bleeding rate (ABR) vs on-demand CFC/bypassing agent (BPA) ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03754790

NCT03754790 | Long-term Safety and Efficacy Study of ... Long-term Safety and Efficacy Study of Fitusiran in Patients With Hemophilia A or B, With or Without Inhibitory Antibodies to Factor VIII or IX (ATLAS-OLE).

8. sciencedirect.com sciencedirect.com/science/article/pii/S2531137924012811

SAFETY AND EFFICACY OF THE FITUSIRAN REVISED ... In this study, the fitusiran AT-DR targeting AT levels of 15%–35% improved the safety profile substantially versus the ODR and maintained bleed protection.

9. sanofi.com sanofi.com/en/media-room/press-releases/2023/2023-04-04-05-00-00-2640246

Press Release: Two fitusiran Phase 3 studies published in ... The ATLAS A/B study published in The Lancet Haematology showed 51% of participants without inhibitors (40 out of 79) who received fitusiran 80mg ...