Fitusiran for Hemophilia

(ATLAS-OLE Trial)

Recruiting at 233 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

281 Participants Needed

Trial Summary

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.

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 those with hemophilia, with or without inhibitors. ^{1 2 3 4 5}

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 along with Fitusiran, indicating the need for caution when combining it with other hemostatic agents. ^{1 2 3 4 6}

How is the drug Fitusiran different from other hemophilia treatments?

Fitusiran is unique because it uses RNA interference to target and lower antithrombin, a natural anticoagulant, which helps rebalance blood clotting in people with hemophilia A or B. 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, reducing the treatment burden and improving bleeding control. ^{1 2 3 4 5}

What is the purpose of this trial?

Primary Objective: To characterize the long-term safety and tolerability of fitusiran Secondary Objectives: * To characterize the efficacy and long-term efficacy of fitusiran as assessed by the frequency of: * Bleeding episodes * Spontaneous bleeding episodes * Joint bleeding episodes * To characterize the effects of fitusiran on health-related quality of life (HRQOL) measures in participants ≥17 years of age

Research Team

Clinical Sciences & Operations

Principal Investigator

Sanofi

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

References

1. 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]

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

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

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

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

4. 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]

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

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

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

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