NCT03997383

Brief Summary

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

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
360

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Sep 2019

Longer than P75 for phase_3

Geographic Reach
22 countries

90 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 24, 2019

Completed
1 day until next milestone

First Posted

Study publicly available on registry

June 25, 2019

Completed
2 months until next milestone

Study Start

First participant enrolled

September 4, 2019

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 20, 2022

Completed
1.3 years until next milestone

Results Posted

Study results publicly available

October 18, 2023

Completed
2.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 24, 2025

Completed
Last Updated

April 20, 2026

Status Verified

March 1, 2026

Enrollment Period

2.8 years

First QC Date

June 24, 2019

Results QC Date

June 20, 2023

Last Update Submit

March 30, 2026

Conditions

Keywords

RNAi therapeuticTransthyretinTTRAmyloidosisCardiomyopathyATTR

Outcome Measures

Primary Outcomes (1)

  • Change From Baseline at Month 12 in Six-Minute Walk Test (6-MWT)

    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 Outcomes (4)

  • Change From Baseline at Month 12 in Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) Score

    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

    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

    Up to Month 12

  • Composite Endpoint of All-cause Mortality and Frequency of All-cause Hospitalizations and Urgent HF Visits in All Participants

    Up to Month 12

Study Arms (2)

Patisiran

EXPERIMENTAL

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

Drug: Patisiran

Placebo

PLACEBO COMPARATOR

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: PlaceboDrug: Patisiran

Interventions

Normal saline (0.9% NaCl) matching volume of patisiran doses will be administered intravenously.

Placebo

Patisiran will be administered by intravenous (IV) infusion.

Also known as: ALN-TTR02, patisiran-lipid nanoparticle (LNP)
PatisiranPlacebo

Eligibility Criteria

Age18 Years - 85 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (90)

Clinical Trial Site

Los Angeles, California, 90048, United States

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Chicago, Illinois, 60637, United States

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Skokie, Illinois, 60076, United States

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Iowa City, Iowa, 52242, United States

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Kansas City, Kansas, 66160, United States

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Baltimore, Maryland, 21224, United States

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Boston, Massachusetts, 02118, United States

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Burlington, Massachusetts, 10805, United States

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Rochester, Minnesota, 55905, United States

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St Louis, Missouri, 63110, United States

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New York, New York, 10029, United States

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New York, New York, 10032, United States

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Cleveland, Ohio, 44195, United States

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Philadelphia, Pennsylvania, 19104, United States

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Philadelphia, Pennsylvania, 19140, United States

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Pittsburgh, Pennsylvania, 15212, United States

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Nashville, Tennessee, 37232, United States

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Dallas, Texas, 75246, United States

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Norfolk, Virginia, 23507, United States

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Buenos Aires, C1039AAO, Argentina

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Buenos Aires, C1428AQK, Argentina

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Córdoba, X5000KEH, Argentina

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Rosario, S2000DSR, Argentina

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Rosario, S2000DTC, Argentina

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Rosario, S2000PBJ, Argentina

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San Juan Bautista, B1888AAE, Argentina

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Santa Fe, S3000FWO, Argentina

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Box Hill, 3128, Australia

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Westmead, 2145, Australia

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Woolloongabba, 4021, Australia

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Aalst, 9300, Belgium

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Hasselt, 3500, Belgium

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Liège, 4000, Belgium

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Roeselare, 8800, Belgium

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Porto Alegre, 90035-030, Brazil

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Ribeirão Preto, 14026-900, Brazil

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Ribeirão Preto, 14048-900, Brazil

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Rio de Janeiro, 22280-000, Brazil

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São Paulo, 04012-909, Brazil

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São Paulo, 05403-000, Brazil

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Sofia, 1680, Bulgaria

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Sofia, 1784, Bulgaria

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Stara Zagora, 6000, Bulgaria

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Providencia/ Santiago, 7500587, Chile

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Brno, 656 91, Czechia

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Prague, 120 00, Czechia

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Prague, 128 08, Czechia

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Prague, 140 21, Czechia

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Aarhus N, 8200, Denmark

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Copenhagen, 2100, Denmark

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Odense C, 5000, Denmark

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Clichy, 92110, France

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Créteil, 94010, France

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Rennes, 35033, France

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Toulouse, 31059, France

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Lai Chi Kok, 999077, Hong Kong

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Bologna, 40138, Italy

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Florence, 50134, Italy

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Messina, 98125, Italy

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Pavia, 27100, Italy

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Bunkyō City, 113-8655, Japan

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Fukuoka, 812-8582, Japan

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Kumamoto, 860-8556, Japan

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Kurume, 830-0011, Japan

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Matsumoto, 390-8621, Japan

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Nagoya, 466-8560, Japan

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Suita, 565-8565, Japan

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Mexico City, 14080, Mexico

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Groningen, 9713 GZ, Netherlands

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Maastricht, 6229 HX, Netherlands

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Christchurch, 8011, New Zealand

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Hamilton, 3204, New Zealand

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Gdansk, 80-382, Poland

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Katowice, 40-635, Poland

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Lódz, 90-127, Poland

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Warsaw, 01-192, Poland

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Warsaw, 04-628, Poland

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Porto, 4099-001, Portugal

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Senhora da Hora, 4464-513, Portugal

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Viseu, 3504-509, Portugal

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Seoul, 3080, South Korea

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Stockholm, 17164, Sweden

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Taipei, 11217, Taiwan

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Bellshill, ML4 3NJ, United Kingdom

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Birmingham, B15 2SQ, United Kingdom

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Cardiff, CF15 9SS, United Kingdom

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Hexham, NE46 1QJ, United Kingdom

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London, NW3 2PF, United Kingdom

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London, SE1 1YR, United Kingdom

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Manchester, M15 6SE, United Kingdom

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Related Publications (2)

  • Mesquita CT, Schwartzmann P, Correia EB, Simoes MV, Biolo A, Duque DR, Jay PY, Fernandes F. Patisiran Treatment in the Brazilian Subpopulation of the Phase 3 APOLLO-B Study in Transthyretin Amyloidosis with Cardiomyopathy: Post Hoc Analysis. Arq Bras Cardiol. 2025 Mar;122(4):e20240568. doi: 10.36660/abc.20240568. English, Portuguese.

  • Maurer MS, Kale P, Fontana M, Berk JL, Grogan M, Gustafsson F, Hung RR, Gottlieb RL, Damy T, Gonzalez-Duarte A, Sarswat N, Sekijima Y, Tahara N, Taylor MS, Kubanek M, Donal E, Palecek T, Tsujita K, Tang WHW, Yu WC, Obici L, Simoes M, Fernandes F, Poulsen SH, Diemberger I, Perfetto F, Solomon SD, Di Carli M, Badri P, White MT, Chen J, Yureneva E, Sweetser MT, Jay PY, Garg PP, Vest J, Gillmore JD; APOLLO-B Trial Investigators. Patisiran Treatment in Patients with Transthyretin Cardiac Amyloidosis. N Engl J Med. 2023 Oct 26;389(17):1553-1565. doi: 10.1056/NEJMoa2300757.

MeSH Terms

Conditions

Amyloidosis, Hereditary, Transthyretin-RelatedAmyloidosisCardiomyopathies

Interventions

patisiran

Condition Hierarchy (Ancestors)

Proteostasis DeficienciesMetabolic DiseasesNutritional and Metabolic DiseasesHeart DiseasesCardiovascular Diseases

Results Point of Contact

Title
Chief Medical Officer
Organization
Alnylam Pharmaceuticals Inc.

Study Officials

  • Medical Director

    Alnylam Pharmaceuticals

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 24, 2019

First Posted

June 25, 2019

Study Start

September 4, 2019

Primary Completion

June 20, 2022

Study Completion

December 24, 2025

Last Updated

April 20, 2026

Results First Posted

October 18, 2023

Record last verified: 2026-03

Data Sharing

IPD Sharing
Will share

Access to Anonymized individual participant data that support these results is made available 12 months after study completion and not less than 12 months after the product and indication have been approved in the US and/or the EU. Access to data may be declined where there is likelihood a patient could be identified or other feasibility issue, where there is a potential conflict of interest, a planned business activities or an actual or potential competitive risk. Data will be provided contingent upon the approval of a research proposal and the execution of a data sharing agreement. Timeframes for data access may vary and can take up to 6 months or more. Requests for access to data can be submitted via the website www.vivli.org. Questions can also be directed to datasharing@alnylam.com.

Locations