Patisiran for Cardiomyopathy

Not currently recruiting at 67 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Alnylam Pharmaceuticals

Must be taking: Tafamidis

Must not be taking: TTR lowering treatment

Disqualifiers: Primary amyloidosis, Heart failure IV, Neuropathy, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of a drug called patisiran for individuals with ATTR amyloidosis with cardiomyopathy, a condition that impairs the heart's ability to pump blood. Participants will receive either patisiran or a placebo to evaluate the drug's efficacy. Ideal candidates for this trial have a confirmed diagnosis of ATTR amyloidosis with cardiomyopathy, have experienced heart failure symptoms or hospitalization in the past, and have not had recent severe heart issues. As a Phase 3 trial, this study represents the final step before FDA approval, providing participants an opportunity to contribute to potentially groundbreaking treatment advancements.

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 mention that participants can be on tafamidis if they have been taking it for at least 6 months and still show disease progression.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that patisiran is generally well-tolerated by patients with ATTR amyloidosis, a condition where abnormal proteins accumulate in the body and affect the heart. Studies have found that patients taking patisiran for several months had better long-term survival rates and required fewer hospital visits compared to those on a placebo. Importantly, these patients maintained their physical abilities and had stable heart health indicators, such as NT-proBNP and Troponin I, which signal heart stress and damage.

Overall, these findings suggest that patisiran is both effective and safe for people with this condition. While all treatments can have side effects, current data indicates that patisiran has a good safety record in similar patient groups. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cardiomyopathy?

Unlike the standard treatments for cardiomyopathy, which typically include beta-blockers, ACE inhibitors, and diuretics, Patisiran offers a novel approach by targeting the genetic root of the condition. Patisiran is unique because it utilizes RNA interference to specifically silence the gene responsible for producing abnormal amyloid proteins that affect heart tissue. This innovative mechanism not only addresses the underlying cause rather than just the symptoms, but it also holds promise for slowing or even halting disease progression, which excites researchers about its potential impact on patient outcomes.

What evidence suggests that patisiran might be an effective treatment for cardiomyopathy?

Research has shown that patisiran can help treat heart problems caused by ATTR amyloidosis. In one study, patients who took patisiran maintained their ability to perform physical activities, indicating their condition did not worsen. Another study found that patients on patisiran experienced better health outcomes and lived longer than those on a placebo. In this trial, participants will receive either patisiran or a placebo. Patisiran also improved mobility and the ability to perform daily activities. It reduced the buildup of harmful proteins in the heart, a major aspect of the illness. Overall, evidence suggests that patisiran can be an effective treatment for this heart condition. ^{1 4 6 7 8}

Who Is on the Research Team?

Medical Director

Principal Investigator

Alnylam Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for adults with a heart condition called ATTR amyloidosis with cardiomyopathy. They should have had heart failure symptoms or hospitalization, be stable without recent cardiovascular hospitalizations, able to walk a short distance in 6 minutes, and not severely affected by other diseases like severe lung disease or arthritis. People who've had certain organ transplants or infections like hepatitis B/C or HIV can't join.

Inclusion Criteria

I have been hospitalized for heart failure before or currently show signs of it.

I can walk more than 150 meters in 6 minutes.

Your blood test for NT-proBNP shows levels above 300 ng/L and below 8500 ng/L. If you have atrial fibrillation, your NT-proBNP levels should be above 600 ng/L and below 8500 ng/L.

Exclusion Criteria

My heart condition is serious and considered high risk.

I need a cane or wheelchair to walk due to nerve damage.

I have been diagnosed with primary or leptomeningeal amyloidosis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive multiple doses of patisiran or placebo in the double-blind period

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants receive multiple doses of patisiran in the open-label extension period

What Are the Treatments Tested in This Trial?

Interventions

• Patisiran
• Placebo

Trial Overview The study tests the effectiveness and safety of Patisiran compared to a placebo in treating ATTR amyloidosis affecting the heart. Participants will either receive Patisiran or an inactive substance without knowing which one they're getting to see if there's an improvement in their heart condition.

How Is the Trial Designed?

Group I: Patisiran Experimental Treatment 1 Intervention

Participants will be administered multiple doses of patisiran in the double-blind and open-label extension period.

Group II: Placebo Placebo Group 2 Interventions

Participants will be administered multiple doses of placebo in the double-blind period. In the open-label extension period, participants will be administered multiple doses of patisiran.

Who Is Running the Clinical Trial?

Alnylam Pharmaceuticals

Lead Sponsor

Trials

81

Recruited

16,100+

Dr. Yvonne Greenstreet

Alnylam Pharmaceuticals

Chief Executive Officer since 2021

MD from the University of Leeds, MBA from INSEAD

Dr. Pushkal Garg

Alnylam Pharmaceuticals

Chief Medical Officer since 2016

MD from Columbia University

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2300757

Patisiran Treatment in Patients with Transthyretin Cardiac ... In this trial, administration of patisiran over a period of 12 months resulted in preserved functional capacity in patients with ATTR cardiac amyloidosis.

2. jamanetwork.com jamanetwork.com/journals/jamaneurology/fullarticle/2828606

Five-Year Results With Patisiran for Hereditary ... Patients who received patisiran in their parent study had better outcomes and survival than those receiving placebo.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11295162/

Effectiveness of patisiran after switching from tafamidis for ... During the 12 months following patisiran initiation, 28.6% of patients experienced improvement in orthostatic intolerance, 57.1% had no change, and 14.3% ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2772963X25002960

Benefits of Patisiran on Functional Capacity in ATTR ... Patisiran demonstrated a statistically significant improvement in functional capacity compared with placebo, evidenced by a treatment benefit with patisiran in ...

5. link.springer.com link.springer.com/article/10.1007/s44337-024-00066-y

A mini review of Patisiran's efficacy in the management ... Findings indicating a reduction in cardiac amyloid burden, regression of cardiac amyloid, and prevention of deterioration in various cardiac ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11894486/

A Randomized Clinical Trial With Open-Label Extension Previously published interim 12-month data showed sustained clinical stability for patients who received patisiran in the parent studies, and ...

7. academic.oup.com academic.oup.com/eurheartj/article/45/Supplement_1/ehae666.1039/7835362

Long-term effects of patisiran on survival and cardiac ... Compared with placebo, patients initially receiving patisiran had better long-term survival and fewer hospitalisations (hazard ratio [95% ...

8. investors.alnylam.com investors.alnylam.com/press-release?id=27561

Alnylam Presents 18-Month Results from the APOLLO-B ... Patients treated with patisiran through 18 months also appear to have maintained relative stability of NT-proBNP and Troponin I levels, measures ...