Fitusiran for Pediatric Hemophilia

(ATLAS-PEDS Trial)

Not currently recruiting at 52 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, fitusiran, for young boys with severe hemophilia A or B, a blood disorder that makes it difficult to stop bleeding. Researchers aim to determine the right dose and assess safety by monitoring side effects and how the body processes the drug. The trial seeks boys under 12 with severe hemophilia and specific antibodies that reduce the effectiveness of standard treatments. Participants will receive fitusiran at regular intervals to evaluate its impact on managing their condition. As a Phase 3 trial, this is the final step before FDA approval, providing participants an opportunity to access a potentially groundbreaking treatment early.

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.

Is there any evidence suggesting that fitusiran is likely to be safe for pediatric patients with hemophilia?

Research has shown that fitusiran, a treatment under study for hemophilia, has promising safety results. In one study, patients who received fitusiran monthly experienced fewer bleeding episodes compared to those using treatments only as needed. This suggests fitusiran could offer a safer and more effective way to manage bleeding in hemophilia.

Another study found that adjusting the fitusiran dosage improved its safety, making it easier for patients to tolerate while still preventing bleeding. The research focused on patient tolerance and found the treatment to be well-tolerated with manageable side effects.

Overall, evidence from these studies suggests that fitusiran is safe and well-tolerated by patients. This is encouraging for those considering joining trials for this treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Fitusiran is unique because it targets antithrombin, a protein that normally inhibits blood clotting, which is a different mechanism compared to standard treatments like factor replacement therapy. This approach is promising because it can potentially increase blood clotting ability without the need for frequent infusions of clotting factors. Researchers are excited about Fitusiran because it offers the possibility of more stable protection against bleeding with less frequent dosing, which could significantly improve the quality of life for individuals with hemophilia.

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

Research has shown that fitusiran, the treatment under study in this trial, is a promising option for hemophilia. In earlier studies, fitusiran greatly reduced the number of bleeding episodes in patients. For example, one study found a 71% reduction in bleeding for patients without inhibitors, meaning patients experienced fewer bleeding incidents. Fitusiran works by lowering a protein called antithrombin, which usually reduces clotting. This action helps the body stop bleeding more effectively. Additionally, the treatment has proven to be safer than traditional therapies. Overall, these findings strongly support fitusiran's effectiveness in managing hemophilia. ^{2 3 4 6 7}

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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

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]

Citations

1. 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.

2. 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) ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03974113

Fitusiran Prophylaxis in Male Pediatric Subjects Aged 1 to ... 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

4. checkrare.com checkrare.com/phase-3-studies-lead-to-approval-of-fitusiran-for-hemophilia-a-and-b/

Phase 3 Studies Lead to Approval of Fitusiran for ... Key results included a 71% bleed reduction in annualized bleed rate (ABR) for patients without inhibitors treated with fitusiran compared to ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40053895/

Safety and efficacy of a fitusiran antithrombin-based dose ... This phase 3 open-label extension study (ATLAS-OLE) evaluated safety and efficacy of an AT-based dose regimen (AT-DR) in males aged ≥12 years with severe ...

6. 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 ...

7. publications.aap.org publications.aap.org/aapgrandrounds/article/50/3/35/193729/Fitusiran-Prophylaxis-Reduces-Bleeding-in

Fitusiran Prophylaxis Reduces Bleeding in Hemophilia ... The authors conclude that fitusiran prophylaxis resulted in a significant reduction of bleeding episodes in males with hemophilia A or B with ...