Vutrisiran vs Patisiran for Amyloidosis

Recruiting at 57 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Alnylam Pharmaceuticals

Disqualifiers: Liver transplant, Other amyloidosis, Heart failure, 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: 3

Duration: 18 months

164 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. However, if you have received prior TTR-lowering treatment, you may not be eligible to participate.

What data supports the effectiveness of the drugs Vutrisiran and Patisiran for treating amyloidosis?

Vutrisiran has shown to significantly reduce transthyretin (TTR) levels in healthy subjects, which is promising for treating amyloidosis. Patisiran has been effective in improving symptoms and quality of life in patients with hereditary transthyretin amyloidosis, even after liver transplantation, by reducing TTR production. ^{1 2 3 4 5}

What is the purpose of this trial?

This trial is testing vutrisiran, an under-the-skin injection, in patients with a genetic condition called hATTR amyloidosis. The medication aims to lower harmful protein levels in their bodies. Vutrisiran is administered as a periodic subcutaneous injection.

Research Team

Medical Director

Principal Investigator

Alnylam Pharmaceuticals

Eligibility Criteria

This trial is for adults aged 18-85 with hereditary transthyretin amyloidosis, a condition where abnormal proteins build up in the body. Participants should have specific levels of neurologic impairment and physical functioning, and not have received other TTR-lowering treatments or had a liver transplant.

Inclusion Criteria

I am mostly able to care for myself.

I have hATTR amyloidosis with a TTR mutation.

My nerve function score is within acceptable limits.

Exclusion Criteria

You have important liver function test abnormalities.

My heart condition significantly limits my physical activity.

I have received treatment to lower TTR levels before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive vutrisiran SC injection every 3 months or patisiran IV injection every 3 weeks during the 18-month Treatment Period

18 months

Every 3 months (SC) or every 3 weeks (IV)

Randomized Treatment Extension (RTE)

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

Ongoing

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Patisiran
• Vutrisiran
• Vutrisiran (ALN-TTRSC02)

Trial Overview The study compares Vutrisiran, given as an injection under the skin every three months, to Patisiran, administered intravenously every three weeks. After 18 months, participants may receive Vutrisiran less frequently in an extension period.

Participant Groups

Group I: Vutrisiran + Vutrisiran (HELIOS-A) Experimental Treatment 1 Intervention

Participants will receive vutrisiran 25 mg subcutaneous (SC) injection once every 3 months (q3M) for 18 months during the Treatment Period followed by vutrisiran 50 mg SC injection once every 6 months (q6M) or vutrisiran 25 mg q3M during the Randomized Treatment Extension (RTE) Period. Upon implementation of Amendment 6, participants receiving vutrisiran SC 50 mg q6M will transition to vutrisiran SC 25 mg q3M at their next scheduled dosing.

Group II: Patisiran + Vutrisiran (HELIOS-A) Active Control 2 Interventions

Participants will receive patisiran 0.3 mg/kg intravenous (IV) infusion once every 3 weeks (q3w) for 18 months during the Treatment Period followed by vutrisiran 50 mg SC injection once q6M or vutrisiran 25 mg q3M during the RTE Period. Upon implementation of Amendment 6, participants receiving vutrisiran SC 50 mg q6M will transition to vutrisiran SC 25 mg q3M at their next scheduled dosing.

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

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

Vutrisiran: First Approval. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Pharmacodynamics of Patisiran in Patients with hATTR Amyloidosis and with Polyneuropathy After Liver Transplantation. [2023]

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

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

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

Patisiran treatment in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy after liver transplantation. [2023]