Back to resultsAPOLLO-B: A Study to Evaluate Patisiran in Participants With Transthyretin Amyloidosis With Cardiomyopathy (ATTR Amyloidosis With Cardiomyopathy)
Primary Purpose
Transthyretin Amyloidosis (ATTR) With Cardiomyopathy
Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Placebo
Patisiran
Sponsored by
About this trial
This is an interventional treatment trial for Transthyretin Amyloidosis (ATTR) With Cardiomyopathy focused on measuring RNAi therapeutic, Transthyretin, TTR, Amyloidosis, Cardiomyopathy, ATTR
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 patients 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
Sites / Locations
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Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Patisiran
Placebo
Arm Description
Participants will be administered multiple doses of patisiran in the double-blind and open-label extension period.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
Full Information
NCT ID
NCT03997383
First Posted
June 24, 2019
Last Updated
October 17, 2023
Sponsor
Alnylam Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT03997383
Brief Title
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
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 4, 2019 (Actual)
Primary Completion Date
June 20, 2022 (Actual)
Study Completion Date
June 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alnylam Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
The purpose of this study is to evaluate the efficacy and safety of patisiran in participants with ATTR amyloidosis with cardiomyopathy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Transthyretin Amyloidosis (ATTR) With Cardiomyopathy
Keywords
RNAi therapeutic, Transthyretin, TTR, Amyloidosis, Cardiomyopathy, ATTR
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
360 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Patisiran
Arm Type
Experimental
Arm Description
Participants will be administered multiple doses of patisiran in the double-blind and open-label extension period.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Normal saline (0.9% NaCl) matching volume of patisiran doses will be administered intravenously.
Intervention Type
Drug
Intervention Name(s)
Patisiran
Other Intervention Name(s)
ALN-TTR02, patisiran-LNP
Intervention Description
Patisiran will be administered by intravenous (IV) infusion.
Primary Outcome Measure Information:
Title
Change From Baseline at Month 12 in Six-Minute Walk Test (6-MWT)
Description
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.
Time Frame
Baseline, Month 12
Secondary Outcome Measure Information:
Title
Change From Baseline at Month 12 in Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) Score
Description
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.
Time Frame
Baseline, Month 12
Title
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
Description
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.
Time Frame
Up to Month 12
Title
Composite Endpoint of All-Cause Mortality and Frequency of All-Cause Hospitalizations and Urgent HF Visits in Participants Not on Tafamidis at Baseline
Description
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.
Time Frame
Up to Month 12
Title
Composite Endpoint of All-cause Mortality and Frequency of All-cause Hospitalizations and Urgent HF Visits in All Participants
Description
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.
Time Frame
Up to Month 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Alnylam Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Clinical Trial Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
Clinical Trial Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Clinical Trial Site
City
Evanston
State/Province
Illinois
ZIP/Postal Code
60201
Country
United States
Facility Name
Clinical Trial Site
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66103-2937
Country
United States
Facility Name
Clinical Trial Site
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Clinical Trial Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
Clinical Trial Site
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Clinical Trial Site
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Clinical Trial Site
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Clinical Trial Site
City
New York
State/Province
New York
ZIP/Postal Code
10034
Country
United States
Facility Name
Clinical Trial Site
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Clinical Trial Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19140
Country
United States
Facility Name
Clinical Trial Site
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Clinical Trial Site
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
Clinical Trial Site
City
Córdoba
Country
Argentina
Facility Name
Clinical Trial Site
City
Rosario
ZIP/Postal Code
S2000DSR
Country
Argentina
Facility Name
Clinical Trial Site
City
Rosario
ZIP/Postal Code
S2000DTC
Country
Argentina
Facility Name
Clinical Trial Site
City
Rosario
ZIP/Postal Code
S2000PBJ
Country
Argentina
Facility Name
Clinical Trial Site
City
Box Hill
Country
Australia
Facility Name
Clinical Trial Site
City
Westmead
Country
Australia
Facility Name
Clinical Trial Site
City
Aalst
Country
Belgium
Facility Name
Clinical Trial Site
City
Hasselt
Country
Belgium
Facility Name
Clinical Trial Site
City
Liège
Country
Belgium
Facility Name
Clinical Trial Site
City
Roeselare
Country
Belgium
Facility Name
Clinical Trial Site
City
Porto Alegre
Country
Brazil
Facility Name
Clinical Trial Site
City
Ribeirão Preto
Country
Brazil
Facility Name
Clinical Trial Site
City
Rio De Janeiro
Country
Brazil
Facility Name
Clinical Trial Site
City
São Paulo
ZIP/Postal Code
05403-000
Country
Brazil
Facility Name
Clinical Trial Site
City
São Paulo
ZIP/Postal Code
14048-900
Country
Brazil
Facility Name
Clinical Trial Site
City
São Paulo
Country
Brazil
Facility Name
Clinical Trial Site
City
Sofia
Country
Bulgaria
Facility Name
Clinical Trial Site
City
Santiago
Country
Chile
Facility Name
Clinical Trial Site
City
Brno
Country
Czechia
Facility Name
Clinical Trial Site
City
Prague
Country
Czechia
Facility Name
Clinical Trial Site
City
Praha 2
Country
Czechia
Facility Name
Clinical Trial Site
City
Praha
Country
Czechia
Facility Name
Clinical Trial Site
City
Aarhus
Country
Denmark
Facility Name
Clinical Trial Site
City
Copenhagen
Country
Denmark
Facility Name
Clinical Trial Site
City
Odense
Country
Denmark
Facility Name
Clinical Trial Site
City
Créteil
Country
France
Facility Name
Clinical Trial Site
City
Rennes
Country
France
Facility Name
Clinical Trial Site
City
Toulouse
Country
France
Facility Name
Clinical Trial Site
City
Lai Chi Kok
Country
Hong Kong
Facility Name
Clinical Trial Site
City
Bologna
Country
Italy
Facility Name
Clinical Trial Site
City
Firenze
Country
Italy
Facility Name
Clinical Trial Site
City
Messina
Country
Italy
Facility Name
Clinical Trial Site
City
Pavia
Country
Italy
Facility Name
Clinical Trial Site
City
Fukuoka
Country
Japan
Facility Name
Clinical Trial Site
City
Kumamoto
Country
Japan
Facility Name
Clinical Trial Site
City
Kurume
Country
Japan
Facility Name
Clinical Trial Site
City
Matsumoto
Country
Japan
Facility Name
Clinical Trial Site
City
Nagoya
Country
Japan
Facility Name
Clinical Trial Site
City
Osaka
Country
Japan
Facility Name
Clinical Trial Site
City
Tokyo
Country
Japan
Facility Name
Clinical Trial Site
City
Seoul
Country
Korea, Republic of
Facility Name
Clinical Trial Site
City
Mexico City
Country
Mexico
Facility Name
Clinical Trial Site
City
Groningen
Country
Netherlands
Facility Name
Clinical Trial Site
City
Maastricht
Country
Netherlands
Facility Name
Clinical Trial Site
City
Christchurch
Country
New Zealand
Facility Name
Clinical Trial Site
City
Hamilton
Country
New Zealand
Facility Name
Clinical Trial Site
City
Viseu
Country
Portugal
Facility Name
Clinical Trial Site
City
Stockholm
Country
Sweden
Facility Name
Clinical Trial Site
City
Taipei
Country
Taiwan
Facility Name
Clinical Trial Site
City
Birmingham
Country
United Kingdom
Facility Name
Clinical Trial Site
City
Cardiff
Country
United Kingdom
Facility Name
Clinical Trial Site
City
Glasgow
Country
United Kingdom
Facility Name
Clinical Trial Site
City
London
Country
United Kingdom
Facility Name
Clinical Trial Site
City
Manchester
Country
United Kingdom
Facility Name
Clinical Trial Site
City
Stockton-on-Tees
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
APOLLO-B: A Study to Evaluate Patisiran in Participants With Transthyretin Amyloidosis With Cardiomyopathy (ATTR Amyloidosis With Cardiomyopathy)
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