Vutrisiran for Transthyretin Amyloidosis with Cardiomyopathy

Recruiting at 100 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Alnylam Pharmaceuticals

Disqualifiers: Primary amyloidosis, NYHA Class IV, 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

Compensation: Varies

Number of Visits: 3

655 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Vutrisiran for treating transthyretin amyloidosis with cardiomyopathy?

Vutrisiran has shown to effectively reduce transthyretin levels in healthy subjects, which is promising for treating transthyretin amyloidosis. Additionally, similar drugs like patisiran have shown positive results in reducing heart-related symptoms in patients with transthyretin cardiac amyloidosis. ^{1 2 3 4 5}

Is Vutrisiran safe for humans?

Vutrisiran has been tested in healthy subjects and showed an acceptable safety profile, with the most common side effect being mild and temporary reactions at the injection site. This suggests it is generally safe for human use. ^{1 4 5 6 7}

How is the drug Vutrisiran different from other treatments for transthyretin amyloidosis with cardiomyopathy?

Vutrisiran is unique because it is a small interfering RNA (siRNA) drug that targets the liver to reduce transthyretin (TTR) protein levels, and it is administered subcutaneously (under the skin) once every three months, which is less frequent than many other treatments. ^{1 2 4 5 8}

What is the purpose of this trial?

This study will evaluate the efficacy and safety of vutrisiran 25 mg administered subcutaneously (SC) once every 3 months (q3M) compared to placebo in patients with ATTR amyloidosis with cardiomyopathy.

Research Team

Medical Director

Principal Investigator

Alnylam Pharmaceuticals

Eligibility Criteria

This trial is for patients with a confirmed diagnosis of transthyretin (ATTR) amyloidosis with cardiomyopathy, which includes inherited or wild-type forms. Participants should have a history of heart failure, evidenced by hospitalization or clinical signs. Those with primary or leptomeningeal amyloidosis, severe polyneuropathy, advanced heart failure, very low kidney function, prior TTR treatments, or other types of cardiomyopathies cannot join.

Inclusion Criteria

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

I have been diagnosed with a type of heart disease caused by transthyretin amyloidosis.

Exclusion Criteria

I have been diagnosed with primary or leptomeningeal amyloidosis.

I have a heart condition not caused by TTR amyloidosis.

I have severe nerve damage affecting my daily activities.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Double-blind Treatment

Participants receive vutrisiran 25 mg SC or placebo once every 3 months

Up to 36 months

Visits every 3 months

Randomized Treatment Extension (RTE)

Participants receive vutrisiran 25 mg SC every 3 months or 50 mg SC every 6 months

Duration not specified

Open-label Extension (OLE)

Participants receive vutrisiran 25 mg SC every 3 months

Duration not specified

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Vutrisiran

Trial Overview The study tests the effectiveness and safety of Vutrisiran given as an injection under the skin every three months compared to a placebo (saline solution). The goal is to see if Vutrisiran can help patients with ATTR amyloidosis affecting the heart.

Participant Groups

Group I: Vutrisiran 25 mg Experimental Treatment 1 Intervention

Participants will receive vutrisiran 25 mg administered subcutaneously (SC) once every 3 months (q3M) during the double-blind (DB) period. After the DB period, participants enter the open-label randomized treatment extension (RTE) period to receive vutrisiran 25 mg SC q3M or vutrisiran 50 mg SC every 6 months (q6M). After implementation of Amendment 4, participants from the DB period will enter the open-label treatment extension (OLE) period to receive vutrisiran 25 mg SC q3M and participants who were previously receiving vutrisiran 50 mg q6M in the RTE period, will be transitioned to vutrisiran 25 mg q3M in the OLE period.

Group II: Placebo Placebo Group 2 Interventions

Participants will receive placebo during the double-blind period. After the DB period, participants enter the RTE period to receive vutrisiran 25 mg SC q3M or vutrisiran 50 mg SC q6M. After implementation of Amendment 4, participants from the DB period will enter the OLE period to receive vutrisiran 25 mg SC q3M and participants who were previously receiving vutrisiran 50 mg q6M in the RTE period, will be transitioned to vutrisiran 25 mg q3M in the OLE period.

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

Findings from Research

A 78-year-old woman with hereditary transthyretin cardiac amyloidosis showed improvement after six months of treatment with patisiran, as indicated by decreased levels of N-terminal pro B-type natriuretic peptide and left ventricular mass index.

Patisiran appears to be a promising disease-modifying treatment for advanced hereditary transthyretin cardiac amyloidosis, but more research with larger groups of patients is needed to confirm its efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patisiran for advanced heart failure with hereditary transthyretin cardiac amyloidosis. Nakamura, M., Imamura, T., Kinugawa, K.[2021]

Vutrisiran, an RNA interference therapy targeting the TTR gene, has been shown to significantly reduce neuropathy impairment in patients with hereditary transthyretin-mediated amyloidosis, based on a pivotal phase 3 study.

The treatment is generally well tolerated, with the main side effects being pain in extremities and arthralgia, and it offers the convenience of subcutaneous administration every three months, making it a practical option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vutrisiran: A Review in Polyneuropathy of Hereditary Transthyretin-Mediated Amyloidosis. Nie, T., Heo, YA., Shirley, M.[2023]

References

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

Single-Dose Pharmacokinetics and Pharmacodynamics of Transthyretin Targeting N-acetylgalactosamine-Small Interfering Ribonucleic Acid Conjugate, Vutrisiran, in Healthy Subjects. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Specific Therapy for Transthyretin Cardiac Amyloidosis: A Systematic Literature Review and Evidence-Based Recommendations. [2021]

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

Overview of Current and Emerging Therapies for Amyloid Transthyretin Cardiomyopathy. [2023]

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

Vutrisiran: First Approval. [2022]

5. Japan pubmed.ncbi.nlm.nih.gov

Patisiran for advanced heart failure with hereditary transthyretin cardiac amyloidosis. [2021]

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

Italian Real-Life Experience of Patients with Hereditary Transthyretin Amyloidosis Treated with Patisiran. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of vutrisiran for patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy: a randomized clinical trial. [2023]

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

Vutrisiran: A Review in Polyneuropathy of Hereditary Transthyretin-Mediated Amyloidosis. [2023]