APOLLO-B: A Study to Evaluate Patisiran in Participants With Transthyretin Amyloidosis With Cardiomyopathy (ATTR Amyloidosis With Cardiomyopathy)

March 8, 2024 updated by: Alnylam Pharmaceuticals

APOLLO-B: A Phase 3, Randomized, Double-blind, Placebo-controlled Multicenter Study to Evaluate the Efficacy and Safety of Patisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy (ATTR Amyloidosis With Cardiomyopathy)

The purpose of this study is to evaluate the efficacy and safety of patisiran in participants with ATTR amyloidosis with cardiomyopathy.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

360

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Córdoba, Argentina
        • Clinical Trial Site
      • Rosario, Argentina, S2000DSR
        • Clinical Trial Site
      • Rosario, Argentina, S2000DTC
        • Clinical Trial Site
      • Rosario, Argentina, S2000PBJ
        • Clinical Trial Site
  • Australia
      • Box Hill, Australia
        • Clinical Trial Site
      • Westmead, Australia
        • Clinical Trial Site
  • Belgium
      • Aalst, Belgium
        • Clinical Trial Site
      • Hasselt, Belgium
        • Clinical Trial Site
      • Liège, Belgium
        • Clinical Trial Site
      • Roeselare, Belgium
        • Clinical Trial Site
  • Brazil
      • Porto Alegre, Brazil
        • Clinical Trial Site
      • Ribeirão Preto, Brazil
        • Clinical Trial Site
      • Rio De Janeiro, Brazil
        • Clinical Trial Site
      • São Paulo, Brazil, 05403-000
        • Clinical Trial Site
      • São Paulo, Brazil, 14048-900
        • Clinical Trial Site
      • São Paulo, Brazil
        • Clinical Trial Site
  • Bulgaria
      • Sofia, Bulgaria
        • Clinical Trial Site
  • Chile
      • Santiago, Chile
        • Clinical Trial Site
  • Czechia
      • Brno, Czechia
        • Clinical Trial Site
      • Prague, Czechia
        • Clinical Trial Site
      • Praha, Czechia
        • Clinical Trial Site
      • Praha 2, Czechia
        • Clinical Trial Site
  • Denmark
      • Aarhus, Denmark
        • Clinical Trial Site
      • Copenhagen, Denmark
        • Clinical Trial Site
      • Odense, Denmark
        • Clinical Trial Site
  • France
      • Créteil, France
        • Clinical Trial Site
      • Rennes, France
        • Clinical Trial Site
      • Toulouse, France
        • Clinical Trial Site
  • Hong Kong
      • Lai Chi Kok, Hong Kong
        • Clinical Trial Site
  • Italy
      • Bologna, Italy
        • Clinical Trial Site
      • Firenze, Italy
        • Clinical Trial Site
      • Messina, Italy
        • Clinical Trial Site
      • Pavia, Italy
        • Clinical Trial Site
  • Japan
      • Fukuoka, Japan
        • Clinical Trial Site
      • Kumamoto, Japan
        • Clinical Trial Site
      • Kurume, Japan
        • Clinical Trial Site
      • Matsumoto, Japan
        • Clinical Trial Site
      • Nagoya, Japan
        • Clinical Trial Site
      • Osaka, Japan
        • Clinical Trial Site
      • Tokyo, Japan
        • Clinical Trial Site
  • Korea, Republic of
      • Seoul, Korea, Republic of
        • Clinical Trial Site
  • Mexico
      • Mexico City, Mexico
        • Clinical Trial Site
  • Netherlands
      • Groningen, Netherlands
        • Clinical Trial Site
      • Maastricht, Netherlands
        • Clinical Trial Site
  • New Zealand
      • Christchurch, New Zealand
        • Clinical Trial Site
      • Hamilton, New Zealand
        • Clinical Trial Site
  • Portugal
      • Viseu, Portugal
        • Clinical Trial Site
  • Sweden
      • Stockholm, Sweden
        • Clinical Trial Site
  • Taiwan
      • Taipei, Taiwan
        • Clinical Trial Site
  • United Kingdom
      • Birmingham, United Kingdom
        • Clinical Trial Site
      • Cardiff, United Kingdom
        • Clinical Trial Site
      • Glasgow, United Kingdom
        • Clinical Trial Site
      • London, United Kingdom
        • Clinical Trial Site
      • Manchester, United Kingdom
        • Clinical Trial Site
      • Stockton-on-Tees, United Kingdom
        • Clinical Trial Site
  • United States
    • California
      • Los Angeles, California, United States, 90048
        • Clinical Trial Site
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Clinical Trial Site
      • Evanston, Illinois, United States, 60201
        • Clinical Trial Site
    • Kansas
      • Kansas City, Kansas, United States, 66103-2937
        • Clinical Trial Site
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Clinical Trial Site
    • Massachusetts
      • Boston, Massachusetts, United States, 02118
        • Clinical Trial Site
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Clinical Trial Site
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Clinical Trial Site
    • New York
      • New York, New York, United States, 10029
        • Clinical Trial Site
      • New York, New York, United States, 10034
        • Clinical Trial Site
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Clinical Trial Site
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19140
        • Clinical Trial Site
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Clinical Trial Site
    • Texas
      • Dallas, Texas, United States, 75246
        • Clinical Trial Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Documented diagnosis of ATTR amyloidosis with cardiomyopathy, classified as either hereditary ATTR amyloidosis with cardiomyopathy or wild-type ATTR amyloidosis with cardiomyopathy
  • Medical history of heart failure with at least 1 prior hospitalization for heart failure, or current clinical evidence (signs and symptoms of heart failure)
  • Clinically stable with no cardiovascular related hospitalizations within 6 weeks of study start
  • Has never taken tafamidis before (tafamidis naïve) or currently on tafamidis for ≥6 months with evidence of disease progression while on tafamidis treatment
  • Able to complete ≥150 m on the 6-minute walk test
  • Screening N-terminal pro B-type natriuretic peptide (NT-proBNP), a blood marker of heart failure severity, >300 ng/L and <8500 ng/L; in participants with permanent or persistent atrial fibrillation, screening NT-proBNP> 600 ng/L and <8500 ng/L

Exclusion Criteria:

  • Known primary amyloidosis (AL) or leptomeningeal amyloidosis.
  • Received prior TTR lowering treatment
  • New York Heart Association heart failure classification of III and at high risk
  • New York Heart Association heart failure classification of IV
  • Neuropathy requiring cane or stick to walk, or is wheelchair bound
  • Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m^2
  • Abnormal liver function
  • Has hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection
  • Has non-amyloid disease that significantly affects ability to walk (e.g., severe chronic obstructive pulmonary disease, severe arthritis, or peripheral vascular disease affecting ambulation)
  • Prior or planned heart, liver, or other organ transplant
  • Other cardiomyopathy not related to ATTR amyloidosis

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Patisiran
Participants will be administered multiple doses of patisiran in the double-blind and open-label extension period.
Drug: Patisiran
Patisiran will be administered by intravenous (IV) infusion.
Other Names:
  • ALN-TTR02
  • patisiran-LNP
Placebo Comparator: Placebo
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.
Drug: Patisiran
Patisiran will be administered by intravenous (IV) infusion.
Other Names:
  • ALN-TTR02
  • patisiran-LNP
Drug: Placebo
Normal saline (0.9% NaCl) matching volume of patisiran doses will be administered intravenously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline at Month 12 in Six-Minute Walk Test (6-MWT)
Time Frame: Baseline, Month 12
Distance in meters walked in 6 minutes, longer distances indicate greater functional capacity. Missing 6MWT values due to non-COVID-19 death or inability to walk due to ATTR disease progression were imputed using the worst 10th percentile change observed in the DB period. Missing 6-MWT values due to other reasons are multiply imputed to create 100 complete datasets. The change from baseline is averaged across the 100 complete datasets.
Baseline, Month 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline at Month 12 in Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) Score
Time Frame: Baseline, Month 12
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.
Baseline, Month 12
Composite Endpoint of All-Cause Mortality, Frequency of Cardiovascular (CV) Events (CV Hospitalizations and Urgent Heart Failure [HF] Visits) and Change From Baseline in 6-MWT Analyzed by Win Ratio
Time Frame: Up to Month 12
The composite endpoint was analyzed using the stratified win ratio method, stratified by baseline tafamidis use. This method combines all-cause mortality, frequency of CV events (CV hospitalizations and HF visits) and change from baseline in 6-MWT in a hierarchical fashion. This method makes within-stratum pairwise comparisons for all patisiran-placebo participant pairs in a sequential manner (first mortality, then CV events, then 6-MWT), with later steps evaluated only in the case of a tie on the prior step. Within each stratum, the win ratio is the total number of 'winners' divided by the total number of 'losers' in the active group. A win ratio >1 represents a favorable outcome for patisiran.
Up to Month 12
Composite Endpoint of All-Cause Mortality and Frequency of All-Cause Hospitalizations and Urgent HF Visits in Participants Not on Tafamidis at Baseline
Time Frame: Up to Month 12
The hazard rate of all-cause mortality and all-cause hospitalizations and urgent HF visits will be compared between treatment groups using an Andersen-Gill model. A hazard ratio <1 represents a favorable outcome for patisiran.
Up to Month 12
Composite Endpoint of All-cause Mortality and Frequency of All-cause Hospitalizations and Urgent HF Visits in All Participants
Time Frame: Up to Month 12
The hazard rate of all-cause mortality and all-cause hospitalizations and urgent HF visits was compared between treatment groups using a modified Andersen-Gill model. A hazard ratio <1 represents a favorable outcome for patisiran.
Up to Month 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alnylam Pharmaceuticals

Investigators

  • Study Director: Medical Director, Alnylam Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 4, 2019

Primary Completion (Actual)

June 20, 2022

Study Completion (Estimated)

March 1, 2027

Study Registration Dates

First Submitted

June 24, 2019

First Submitted That Met QC Criteria

June 24, 2019

First Posted (Actual)

June 25, 2019

Study Record Updates

Last Update Posted (Actual)

March 12, 2024

Last Update Submitted That Met QC Criteria

March 8, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ALN-TTR02-011
  • 2019-001458-24 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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