APOLLO-B: A Study to Evaluate Patisiran in Participants With Transthyretin Amyloidosis With Cardiomyopathy (ATTR Amyloidosis With Cardiomyopathy)
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| ClinicalTrials.gov Identifier: NCT03997383 |
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Recruitment Status :
Active, not recruiting
First Posted : June 25, 2019
Results First Posted : October 18, 2023
Last Update Posted : April 22, 2024
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Sponsor:
Alnylam Pharmaceuticals
Information provided by (Responsible Party):
Alnylam Pharmaceuticals
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Brief Summary:
The purpose of this study is to evaluate the efficacy and safety of patisiran in participants with ATTR amyloidosis with cardiomyopathy.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Transthyretin Amyloidosis (ATTR) With Cardiomyopathy | Drug: Placebo Drug: Patisiran | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 360 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| 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) |
| Actual Study Start Date : | September 4, 2019 |
| Actual Primary Completion Date : | June 20, 2022 |
| Estimated Study Completion Date : | March 2027 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Transthyretin amyloidosis
Drug Information
available for:
Patisiran
| Arm | Intervention/treatment |
|---|---|
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Experimental: Patisiran
Participants will be administered multiple doses of patisiran in the double-blind and open-label extension period.
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Drug: Patisiran
Patisiran will be administered by intravenous (IV) infusion.
Other Names:
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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.
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Drug: Placebo
Normal saline (0.9% NaCl) matching volume of patisiran doses will be administered intravenously. Drug: Patisiran Patisiran will be administered by intravenous (IV) infusion.
Other Names:
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Primary Outcome Measures :
- 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.
Secondary Outcome Measures :
- 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.
- 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.
- 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.
- 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.
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years to 85 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03997383
Locations
Show 69 study locations
Sponsors and Collaborators
Alnylam Pharmaceuticals
Investigators
| Study Director: | Medical Director | Alnylam Pharmaceuticals |
Study Documents (Full-Text)
Documents provided by Alnylam Pharmaceuticals:
Documents provided by Alnylam Pharmaceuticals:
Study Protocol [PDF] June 30, 2021
Statistical Analysis Plan [PDF] June 27, 2022
| Responsible Party: | Alnylam Pharmaceuticals |
| ClinicalTrials.gov Identifier: | NCT03997383 |
| Other Study ID Numbers: |
ALN-TTR02-011 2019-001458-24 ( EudraCT Number ) |
| First Posted: | June 25, 2019 Key Record Dates |
| Results First Posted: | October 18, 2023 |
| Last Update Posted: | April 22, 2024 |
| Last Verified: | April 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | 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. Data will be provided contingent upon the approval of a research proposal and the execution of a data sharing agreement. Requests for access to data can be submitted via the website www.vivli.org. |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Alnylam Pharmaceuticals:
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RNAi therapeutic Transthyretin TTR |
Amyloidosis Cardiomyopathy ATTR |
Additional relevant MeSH terms:
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Amyloid Neuropathies, Familial Cardiomyopathies Amyloidosis Heart Diseases Cardiovascular Diseases Proteostasis Deficiencies Metabolic Diseases Heredodegenerative Disorders, Nervous System |
Neurodegenerative Diseases Nervous System Diseases Amyloid Neuropathies Peripheral Nervous System Diseases Neuromuscular Diseases Genetic Diseases, Inborn Amyloidosis, Familial Metabolism, Inborn Errors |