Fitusiran for Hemophilia

(ATLAS-NEO Trial)

Not currently recruiting at 113 trial locations

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

Age: Any Age

Sex: Male

Trial Phase: Phase 3

Sponsor: Sanofi

Disqualifiers: Thromboembolism, Liver disease, HIV, 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: 39

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called fitusiran for individuals with hemophilia A or B, a condition that impairs blood clotting and leads to frequent bleeding episodes. The trial aims to assess how fitusiran affects the frequency of these episodes compared to standard treatments. Participants will switch from their current treatment to fitusiran to determine if it reduces bleeding. Those with severe hemophilia A or B who experience frequent bleeding episodes despite current treatments might be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the potential availability of a new treatment.

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

The trial does not specify if you need to stop your current medications. However, since participants are switching from their prior standard of care treatment, it is likely that you will need to change your current hemophilia treatment to fitusiran.

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

Research has shown that fitusiran is generally safe for people with hemophilia. Studies have found that it can help control bleeding over the long term. Most reported side effects were mild, such as headaches or injection site reactions, occurring in about 5% of participants. Importantly, recent research has improved fitusiran's use, enhancing safety while effectively controlling bleeding. Overall, evidence suggests that fitusiran is safe for people with hemophilia, but discussing any concerns with a healthcare provider is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Fitusiran is unique because it targets antithrombin, reducing its levels to help rebalance clotting in people with hemophilia, unlike traditional treatments that directly replace missing clotting factors or use bypassing agents. This mechanism can potentially reduce the frequency of bleeding episodes more effectively. Additionally, Fitusiran is administered subcutaneously, either once monthly or every other month, offering a more convenient dosing schedule compared to the frequent infusions required by standard treatments. Researchers are excited about Fitusiran because it could simplify hemophilia management and improve patient quality of life.

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

Research has shown that fitusiran can greatly reduce bleeding in people with hemophilia. In earlier studies, patients who received monthly fitusiran injections experienced fewer bleeding episodes compared to those who used treatments only when needed. Another study found that fitusiran effectively lowered the number of bleeding incidents over a year, meaning participants bled less often. The treatment works by reducing the amount of antithrombin, a protein that usually slows down blood clotting, which helps the blood to clot more easily. Overall, fitusiran appears promising for better bleed control in people with hemophilia. Participants in this trial will receive fitusiran prophylaxis either once every other month or once monthly. ^{4 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 male teens and adults with severe Hemophilia A or B, who've had at least 4 bleeding episodes in the last 6 months. They must be willing to follow study rules and give consent. Those with liver disease, thrombophilic disorders, certain viral infections, low CD4 counts if HIV positive, poor kidney function, other bleeding disorders besides hemophilia or a history of blood clots can't join.

Inclusion Criteria

I have severe hemophilia A or B, confirmed by tests or medical records.

I've needed treatment for bleeding at least 4 times in the last 6 months.

Willing and able to comply with the study requirements and to provide written informed consent and assent in the case of participants under the age of legal consent, per local and national requirements

Exclusion Criteria

I have had blood clots not related to a vein catheter.

Co-existing thrombophilic disorder

Known to be HIV positive with CD4 count <200 cells/μL

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

8 weeks

Standard of Care (SOC)

Participants receive on-demand or prophylactic treatment with clotting factor concentrates (CFCs) or bypassing agents (BPAs)

24 weeks

3 visits (in-person), 12 visits (telephone)

Fitusiran Treatment

Participants receive subcutaneous fitusiran prophylaxis once every other month or once monthly

144 weeks

36 visits (in-person), 72 visits (telephone)

Antithrombin (AT) Follow-up

Participants are monitored for antithrombin recovery after treatment

24 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Fitusiran

Trial Overview The trial tests Fitusiran injections under the skin against standard treatments (clotting factors or bypassing agents) for preventing bleeds in Hemophilia patients. It's an open-label study where participants switch from their current treatment to Fitusiran for about three years after a six-month observation period on their usual care.

How Is the Trial Designed?

Group I: All participants Experimental Treatment 3 Interventions

In standard of care (SOC) period, participants will receive on-demand or prophylactic treatment with clotting factor concentrates (CFCs) or bypassing agents (BPAs) for 6 months (from Day -168 to Day -1). In fitusiran treatment period, participants will receive subcutaneous fitusiran prophylaxis once every other month (Q2M) or once monthly (QM) for 36 months (from Day 1 to Day 1009). In case of bleeding events participants will receive IV CFCs or BPAs. Participants may receive Antithrombin concentrate (ATIIIC) as rescue medicine. .

Who Is Running the Clinical Trial?

Sanofi

Lead Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

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]

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]

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]

Citations

1. 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) ...

2. 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 ...

3. 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 ...

4. 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 ...

5. 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.

6. 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 ... Fitusiran prophylaxis maintained long-term bleeding control in participants with hemophilia A or B, with or without inhibitors.

7. sanofi.com sanofi.com/en/media-room/press-releases/2020/2020-06-19-13-00-00-2050713

Sanofi announces positive long-term efficacy and safety ... Long-term exploratory data show prophylactic treatment with fitusiran provides a sustained reduction in annual bleed rates in moderate to severe ...

8. pro.campus.sanofi pro.campus.sanofi/us/products/qfitlia/safety

QFITLIA® (fitusiran) Safety | For US HCPs The safety of Qfitlia has been extensively studied in the largest hemophilia preapproval clinical program1,2. Adverse reactions reported in ≥5% of patients ...

9. 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).