HELIOS-B: A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy

• ClinicalTrials.gov Identifier: NCT04153149
• Recruitment Status: Active, not recruiting
• First Posted: November 6, 2019
• Last Update Posted: February 13, 2024
• Sponsor: Alnylam Pharmaceuticals
• Information provided by (Responsible Party): Alnylam Pharmaceuticals

Tracking Information

• First Submitted Date: November 4, 2019
• First Posted Date: November 6, 2019
• Last Update Posted Date: February 13, 2024
• Actual Study Start Date: November 26, 2019
• Estimated Primary Completion Date: February 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 1, 2020)

Composite Endpoint of All-Cause Mortality and Recurrent Cardiovascular (CV) Events (CV Hospitalizations and Urgent Heart Failure [HF] Visits) [ Time Frame: 30-36 months ]

All-cause mortality and recurrent CV events (CV hospitalizations and urgent HF visits) will be compared between treatment groups using an Andersen-Gill model.

Original Primary Outcome Measures (submitted: November 4, 2019)

Composite Endpoint of All-Cause Mortality and Frequency of Recurrent Cardiovascular (CV) Hospitalizations [ Time Frame: 30-36 months ]

All-cause mortality and frequency of CV hospitalizations will be compared between treatment groups using an Andersen-Gill model.

Current Secondary Outcome Measures (submitted: July 1, 2020)

• Change from Baseline in 6-Minute Walk Test (6-MWT) at Month 30 [ Time Frame: Baseline, Month 30 ]
• Change from Baseline in the Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) at Month 30 [ Time Frame: Baseline, Month 30 ]
  The KCCQ is a 23-item self-administered questionnaire quantifying 6 domains (symptoms, physical function, quality of life, social limitation, self-efficacy, and symptom stability) and 2 summary scores (clinical and overall summary [OS]). Scores are transformed to a range of 0-100, in which higher scores reflect better health status.
• Change from Baseline in Mean Left Ventricular (LV) Wall Thickness by Echocardiographic Assessment at Month 30 [ Time Frame: Baseline, Month 30 ]
• Change from Baseline in Global Longitudinal Strain by Echocardiographic Assessment at Month 30 [ Time Frame: Baseline and Month 30 ]
• Composite Endpoint of All-Cause Mortality and Recurrent All-cause Hospitalizations and Urgent HF Visits [ Time Frame: 30-36 months ]
  All-cause mortality and recurrent all-cause hospitalizations and urgent HF visits will be compared between treatment groups using an Andersen-Gill model.
• All-cause Mortality [ Time Frame: 30-36 months ]
• Rate of Recurrent CV Events (CV Hospitalizations and Urgent HF Visits) [ Time Frame: 30-36 months ]
• Change from Baseline in N-terminal prohormone B-type Natriuretic Peptide (NTproBNP) at Month 30 [ Time Frame: Baseline, Month 30 ]

Original Secondary Outcome Measures (submitted: November 4, 2019)

• Change from Baseline in 6-Minute Walk Test (6-MWT) at Month 30 [ Time Frame: Baseline, Month 30 ]
• Change from Baseline in the Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) at Month 30 [ Time Frame: Baseline, Month 30 ]
  The KCCQ is a 23-item self-administered questionnaire quantifying 6 domains (symptoms, physical function, quality of life, social limitation, self-efficacy, and symptom stability) and 2 summary scores (clinical and overall summary [OS]). Scores are transformed to a range of 0-100, in which higher scores reflect better health status.
• Change from Baseline in Mean Left Ventricular (LV) Wall Thickness by Echocardiographic Assessment at Month 30 [ Time Frame: Baseline, Month 30 ]
• Change from Baseline in Global Longitudinal Strain by Echocardiographic Assessment at Month 30 [ Time Frame: Baseline and Month 30 ]
• Composite Endpoint of All-Cause Mortality and Recurrent All-cause Hospitalizations [ Time Frame: 30-36 months ]
  All-cause mortality and frequency of recurrent all-cause hospitalizations will be compared between treatment groups using an Andersen-Gill model.
• All-cause Mortality [ Time Frame: 30-36 months ]
• Frequency of Recurrent CV Hospitalizations [ Time Frame: 30-36 months ]
• Change from Baseline in N-terminal prohormone B-type Natriuretic Peptide (NTproBNP) at Month 30 [ Time Frame: Baseline, Month 30 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: HELIOS-B: A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy
• Official Title: HELIOS-B: A Phase 3, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy (ATTR Amyloidosis With Cardiomyopathy)
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Transthyretin Amyloidosis (ATTR) With Cardiomyopathy

Intervention

• Drug: Vutrisiran
  Vutrisiran 25 mg will be administered by SC injection q3M.
  Other Name: ALN-TTRSC02
• Drug: Sterile Normal Saline (0.9% NaCl)
  Sterile normal saline (0.9% NaCl) will be administered by SC injection q3M.

Study Arms

• Experimental: Vutrisiran 25 mg
  Participants will receive vutrisiran 25 mg administered subcutaneously (SC) once every 3 months (q3M) during the double-blind period.
  Intervention: Drug: Vutrisiran
• Placebo Comparator: Placebo
  Participants will receive placebo during the double-blind period.
  Intervention: Drug: Sterile Normal Saline (0.9% NaCl)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: August 17, 2021): 655
• Original Estimated Enrollment (submitted: November 4, 2019): 600
• Estimated Study Completion Date: December 2026
• Estimated Primary Completion Date: February 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Has a documented diagnosis of transthyretin (ATTR) amyloidosis with cardiomyopathy, classified as either hereditary ATTR (hATTR) amyloidosis with cardiomyopathy or wild-type ATTR (wtATTR) amyloidosis with cardiomyopathy meeting pre-specified diagnostic criteria
• Has medical history of heart failure (HF) with at least 1 prior hospitalization for HF OR clinical evidence of HF

Exclusion Criteria:

• Has known primary amyloidosis or leptomeningeal amyloidosis
• Has New York Heart Association (NYHA) Class IV heart failure
• Has NYHA Class III heart failure AND is at high risk based on pre-specified criteria
• Has a polyneuropathy disability (PND) Score IIIa, IIIb, or IV at the Screening visit
• Has estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m^2
• Has received prior TTR-lowering treatment
• Has other non-TTR cardiomyopathy, hypertensive cardiomyopathy, cardiomyopathy due to valvular heart disease, or cardiomyopathy due to ischemic heart disease

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Austria, Belgium, Canada, Croatia, Czechia, Denmark, France, Germany, Hungary, Ireland, Israel, Japan, Korea, Republic of, Latvia, Lithuania, Netherlands, Norway, Peru, Poland, Portugal, Spain, Sweden, United Kingdom, United States
• Removed Location Countries: Colombia, Lebanon, Malaysia, Moldova, Republic of, Saudi Arabia, Slovenia, Thailand

Administrative Information

• NCT Number: NCT04153149
• Other Study ID Numbers: ALN-TTRSC02-003; 2019-003153-28 ( EudraCT Number )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Alnylam Pharmaceuticals
• Original Responsible Party: Same as current
• Current Study Sponsor: Alnylam Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Alnylam Pharmaceuticals

• PRS Account: Alnylam Pharmaceuticals
• Verification Date: February 2024