Fitusiran for Hemophilia

(ATLAS-NEO Trial)

Recruiting at 98 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

79 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests fitusiran, a medication that helps reduce bleeding in male adults and adolescents with hemophilia A or B. It works by lowering antithrombin levels to improve blood clotting.

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 Fitusiran generally safe for humans?

Fitusiran is generally well tolerated, with minor local injection site reactions reported. However, there was a case of fatal thrombosis (blood clot) in a patient with severe hemophilia A who used high doses of clotting factor with fitusiran, indicating the need for caution when combining treatments. ^{1 2 3 4 5}

How does the drug Fitusiran differ from other hemophilia treatments?

Fitusiran is unique because it uses RNA interference to target and lower antithrombin, which helps rebalance blood clotting in people with hemophilia A or B, regardless of inhibitor status. Unlike traditional treatments that require frequent intravenous infusions of clotting factors, Fitusiran is administered subcutaneously (under the skin) and can be given weekly or monthly, potentially reducing the treatment burden. ^{1 3 4 5 6}

What data supports the effectiveness of the drug Fitusiran for treating hemophilia?

Research shows that Fitusiran helps reduce bleeding in people with hemophilia A and B by lowering antithrombin levels, which improves blood clotting. Clinical trials have demonstrated that Fitusiran can decrease the number of bleeding episodes, making it a promising treatment option for hemophilia patients. ^{1 3 4 5 6}

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

Co-existing thrombophilic disorder

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

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

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]

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]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of fitusiran prophylaxis in people with haemophilia A or haemophilia B with inhibitors (ATLAS-INH): a multicentre, open-label, randomised phase 3 trial. [2023]

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

Antithrombin lowering in hemophilia: a closer look at fitusiran. [2023]

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

An investigational RNAi therapeutic targeting antithrombin for the treatment of hemophilia A and B. [2021]

4. England 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. [2023]

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

Targeting of Antithrombin in Hemophilia A or B with RNAi Therapy. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Current challenges of pharmacovigilance in bleeding disorders: converting the burden to benefit. [2013]