Clinical trial NCT03997383: APOLLO-B: A Study to Evaluate Patisiran in Participants With Transthyretin Amyloidosis With Cardiomyopathy (ATTR Amyloidosis With Cardiomyopathy)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Transthyretin Amyloidosis (ATTR) With Cardiomyopathy
Keywords: RNAi therapeutic
Transthyretin
TTR
Amyloidosis
Cardiomyopathy
ATTR
Lead sponsor: Alnylam Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2019-06-25
Enrollment: 360
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline at Month 12 in Six-Minute Walk Test (6-MWT)
timeFrame: Baseline, Month 12
Secondary outcomes:
measure: Change From Baseline at Month 12 in Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) Score
timeFrame: Baseline, Month 12
measure: 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
timeFrame: Up to Month 12
measure: Composite Endpoint of All-Cause Mortality and Frequency of All-Cause Hospitalizations and Urgent HF Visits in Participants Not on Tafamidis at Baseline
timeFrame: Up to Month 12
measure: Composite Endpoint of All-cause Mortality and Frequency of All-cause Hospitalizations and Urgent HF Visits in All Participants
timeFrame: Up to Month 12
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Clinical Trial Site
state: California
city: Chicago
country: United States
facility: Clinical Trial Site
state: Illinois
city: Evanston
country: United States
facility: Clinical Trial Site
state: Illinois
city: Kansas City
country: United States
facility: Clinical Trial Site
state: Kansas
city: Baltimore
country: United States
facility: Clinical Trial Site
state: Maryland
city: Boston
country: United States
facility: Clinical Trial Site
state: Massachusetts
city: Rochester
country: United States
facility: Clinical Trial Site
state: Minnesota
city: Saint Louis
country: United States
facility: Clinical Trial Site
state: Missouri
city: New York
country: United States
facility: Clinical Trial Site
state: New York
city: New York
country: United States
facility: Clinical Trial Site
state: New York
city: Cleveland
country: United States
facility: Clinical Trial Site
state: Ohio
city: Philadelphia
country: United States
facility: Clinical Trial Site
state: Pennsylvania
city: Nashville
country: United States
facility: Clinical Trial Site
state: Tennessee
city: Dallas
country: United States
facility: Clinical Trial Site
state: Texas
city: Córdoba
country: Argentina
facility: Clinical Trial Site
city: Rosario
country: Argentina
facility: Clinical Trial Site
city: Rosario
country: Argentina
facility: Clinical Trial Site
city: Rosario
country: Argentina
facility: Clinical Trial Site
city: Box Hill
country: Australia
facility: Clinical Trial Site
city: Westmead
country: Australia
facility: Clinical Trial Site
city: Aalst
country: Belgium
facility: Clinical Trial Site
city: Hasselt
country: Belgium
facility: Clinical Trial Site
city: Liège
country: Belgium
facility: Clinical Trial Site
city: Roeselare
country: Belgium
facility: Clinical Trial Site
city: Porto Alegre
country: Brazil
facility: Clinical Trial Site
city: Ribeirão Preto
country: Brazil
facility: Clinical Trial Site
city: Rio De Janeiro
country: Brazil
facility: Clinical Trial Site
city: São Paulo
country: Brazil
facility: Clinical Trial Site
city: São Paulo
country: Brazil
facility: Clinical Trial Site
city: São Paulo
country: Brazil
facility: Clinical Trial Site
city: Sofia
country: Bulgaria
facility: Clinical Trial Site
city: Santiago
country: Chile
facility: Clinical Trial Site
city: Brno
country: Czechia
facility: Clinical Trial Site
city: Prague
country: Czechia
facility: Clinical Trial Site
city: Praha 2
country: Czechia
facility: Clinical Trial Site
city: Praha
country: Czechia
facility: Clinical Trial Site
city: Aarhus
country: Denmark
facility: Clinical Trial Site
city: Copenhagen
country: Denmark
facility: Clinical Trial Site
city: Odense
country: Denmark
facility: Clinical Trial Site
city: Créteil
country: France
facility: Clinical Trial Site
city: Rennes
country: France
facility: Clinical Trial Site
city: Toulouse
country: France
facility: Clinical Trial Site
city: Lai Chi Kok
country: Hong Kong
facility: Clinical Trial Site
city: Bologna
country: Italy
facility: Clinical Trial Site
city: Firenze
country: Italy
facility: Clinical Trial Site
city: Messina
country: Italy
facility: Clinical Trial Site
city: Pavia
country: Italy
facility: Clinical Trial Site
city: Fukuoka
country: Japan
facility: Clinical Trial Site
city: Kumamoto
country: Japan
facility: Clinical Trial Site
city: Kurume
country: Japan
facility: Clinical Trial Site
city: Matsumoto
country: Japan
facility: Clinical Trial Site
city: Nagoya
country: Japan
facility: Clinical Trial Site
city: Osaka
country: Japan
facility: Clinical Trial Site
city: Tokyo
country: Japan
facility: Clinical Trial Site
city: Seoul
country: Korea, Republic of
facility: Clinical Trial Site
city: Mexico City
country: Mexico
facility: Clinical Trial Site
city: Groningen
country: Netherlands
facility: Clinical Trial Site
city: Maastricht
country: Netherlands
facility: Clinical Trial Site
city: Christchurch
country: New Zealand
facility: Clinical Trial Site
city: Hamilton
country: New Zealand
facility: Clinical Trial Site
city: Viseu
country: Portugal
facility: Clinical Trial Site
city: Stockholm
country: Sweden
facility: Clinical Trial Site
city: Taipei
country: Taiwan
facility: Clinical Trial Site
city: Birmingham
country: United Kingdom
facility: Clinical Trial Site
city: Cardiff
country: United Kingdom
facility: Clinical Trial Site
city: Glasgow
country: United Kingdom
facility: Clinical Trial Site
city: London
country: United Kingdom
facility: Clinical Trial Site
city: Manchester
country: United Kingdom
facility: Clinical Trial Site
city: Stockton-on-Tees
country: United Kingdom
facility: Clinical Trial Site
Study officials:
affiliation: Alnylam Pharmaceuticals
name: Medical Director
role: STUDY_DIRECTOR
References: