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

Transthyretin Amyloidosis (ATTR) With Cardiomyopathy Clinical Trial

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03997383
• Other study ID #: ALN-TTR02-011
• Secondary ID: 2019-001458-24
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: September 4, 2019
• Est. completion date: March 2027

Study information

• Verified date: May 2024
• Source: Alnylam Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 360
• Est. completion date: March 2027
• Est. primary completion date: June 20, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Amyloid Neuropathies, Familial
• Amyloidosis
• Cardiomyopathies
• Transthyretin Amyloidosis (ATTR) With Cardiomyopathy

Intervention

Drug:
• Placebo
Normal saline (0.9% NaCl) matching volume of patisiran doses will be administered intravenously.
• Patisiran
Patisiran will be administered by intravenous (IV) infusion.

Locations

Country	Name	City	State
Argentina	Clinical Trial Site	Córdoba
Argentina	Clinical Trial Site	Rosario
Argentina	Clinical Trial Site	Rosario
Argentina	Clinical Trial Site	Rosario
Australia	Clinical Trial Site	Box Hill
Australia	Clinical Trial Site	Westmead
Belgium	Clinical Trial Site	Aalst
Belgium	Clinical Trial Site	Hasselt
Belgium	Clinical Trial Site	Liège
Belgium	Clinical Trial Site	Roeselare
Brazil	Clinical Trial Site	Porto Alegre
Brazil	Clinical Trial Site	Ribeirão Preto
Brazil	Clinical Trial Site	Rio De Janeiro
Brazil	Clinical Trial Site	São Paulo
Brazil	Clinical Trial Site	São Paulo
Brazil	Clinical Trial Site	São Paulo
Bulgaria	Clinical Trial Site	Sofia
Chile	Clinical Trial Site	Santiago
Czechia	Clinical Trial Site	Brno
Czechia	Clinical Trial Site	Prague
Czechia	Clinical Trial Site	Praha
Czechia	Clinical Trial Site	Praha 2
Denmark	Clinical Trial Site	Aarhus
Denmark	Clinical Trial Site	Copenhagen
Denmark	Clinical Trial Site	Odense
France	Clinical Trial Site	Créteil
France	Clinical Trial Site	Rennes
France	Clinical Trial Site	Toulouse
Hong Kong	Clinical Trial Site	Lai Chi Kok
Italy	Clinical Trial Site	Bologna
Italy	Clinical Trial Site	Firenze
Italy	Clinical Trial Site	Messina
Italy	Clinical Trial Site	Pavia
Japan	Clinical Trial Site	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
Korea, Republic of	Clinical Trial Site	Seoul
Mexico	Clinical Trial Site	Mexico City
Netherlands	Clinical Trial Site	Groningen
Netherlands	Clinical Trial Site	Maastricht
New Zealand	Clinical Trial Site	Christchurch
New Zealand	Clinical Trial Site	Hamilton
Portugal	Clinical Trial Site	Viseu
Sweden	Clinical Trial Site	Stockholm
Taiwan	Clinical Trial Site	Taipei
United Kingdom	Clinical Trial Site	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 States	Clinical Trial Site	Baltimore	Maryland
United States	Clinical Trial Site	Boston	Massachusetts
United States	Clinical Trial Site	Chicago	Illinois
United States	Clinical Trial Site	Cleveland	Ohio
United States	Clinical Trial Site	Dallas	Texas
United States	Clinical Trial Site	Evanston	Illinois
United States	Clinical Trial Site	Kansas City	Kansas
United States	Clinical Trial Site	Los Angeles	California
United States	Clinical Trial Site	Nashville	Tennessee
United States	Clinical Trial Site	New York	New York
United States	Clinical Trial Site	New York	New York
United States	Clinical Trial Site	Philadelphia	Pennsylvania
United States	Clinical Trial Site	Rochester	Minnesota
United States	Clinical Trial Site	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Alnylam Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Bulgaria,  Chile,  Czechia,  Denmark,  France,  Hong Kong,  Italy,  Japan,  Korea, Republic of,  Mexico,  Netherlands,  New Zealand,  Portugal,  Sweden,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change From Baseline at Month 12 in Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) Score	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
Secondary	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	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
Secondary	Composite Endpoint of All-Cause Mortality and Frequency of All-Cause Hospitalizations and Urgent HF Visits in Participants Not on Tafamidis at Baseline	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
Secondary	Composite Endpoint of All-cause Mortality and Frequency of All-cause Hospitalizations and Urgent HF Visits in All Participants	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