Fitusiran for Pediatric Hemophilia

(ATLAS-PEDS Trial)

Recruiting at 44 trial locations

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

Age: < 18

Sex: Male

Trial Phase: Phase 3

Sponsor: Genzyme, a Sanofi Company

Must not be taking: Emicizumab

Disqualifiers: Bleeding disorders, 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: Unknown

Duration: 256 weeks

32 Participants Needed

Trial Summary

What is the purpose of this trial?

Primary Objective: - To confirm appropriate dose levels of fitusiran when administered to male pediatric participants (ages 1 to \<12 years of age) with severe hemophilia A or B Secondary Objectives: * To characterize the safety and tolerability * To determine fitusiran plasma concentrations at selected time points

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 have used emicizumab (Hemlibra®) within 6 months before the trial starts.

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

Research shows that Fitusiran, which targets a protein called antithrombin, helps reduce bleeding in people with hemophilia A and B by improving blood clotting. Clinical trials have demonstrated that it lowers the rate of bleeding episodes, making it a promising treatment option. ^{1 2 3 4 5}

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 6}

Research Team

Clinical Sciences & Operations

Principal Investigator

Sanofi

Eligibility Criteria

This trial is for male children aged 1 to less than 12 with severe hemophilia A or B. They must have a history of inhibitor antibodies and meet specific blood test criteria. Participants need good vein access for blood draws, weigh between 8 to <45 kg, and be able to follow the study plan with parental consent.

Inclusion Criteria

My latest inhibitor test result is below 0.6 BU/mL, but I have records showing two previous results of 0.6 BU/mL or higher.

Severe hemophilia A or B (Factor VIII (FVIII) <1% or Factor IX (FIX) ≤2%)

Willing and able to comply with the study requirements and to provide signed written informed consent obtained from parent(s)/legal guardian (hereinafter the "parent") and written or oral assent obtained from participant, per local and national requirements

Exclusion Criteria

I have a blood clotting disorder.

I have Hepatitis B.

I currently have acute Hepatitis A or E.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a selected dose of fitusiran at regular intervals

256 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

24 weeks

Treatment Details

Interventions

• Fitusiran

Trial Overview The trial is testing appropriate dose levels of Fitusiran in young boys with severe hemophilia A or B. It aims to confirm dosing, assess safety and tolerability, and measure how much drug stays in the bloodstream over time.

Participant Groups

Group I: Fitusiran Experimental Treatment 1 Intervention

Participants will receive a selected dose of fitusiran at regular intervals, as per study protocol

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

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]

References

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

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

2. 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]

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

RNAi for the Treatment of People with Hemophilia: Current Evidence and Patient Selection. [2023]

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

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