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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03997383




Registration number
NCT03997383
Ethics application status
Date submitted
24/06/2019
Date registered
25/06/2019
Date last updated
19/04/2021

Titles & IDs
Public title
APOLLO-B: A Study to Evaluate Patisiran in Participants With Transthyretin Amyloidosis With Cardiomyopathy (ATTR Amyloidosis With Cardiomyopathy)
Scientific 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)
Secondary ID [1] 0 0
2019-001458-24
Secondary ID [2] 0 0
ALN-TTR02-011
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Transthyretin Amyloidosis (ATTR) With Cardiomyopathy 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Neurological 0 0 0 0
Other neurological disorders
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders
Metabolic and Endocrine 0 0 0 0
Metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Placebo
Treatment: Drugs - Patisiran

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

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.


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

Treatment: Drugs: Patisiran
Patisiran will be administered by intravenous (IV) infusion.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change from Baseline at Month 12 in Six-Minute Walk Test (6-MWT)
Timepoint [1] 0 0
Baseline, Month 12
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Baseline, Month 12
Secondary outcome [2] 0 0
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 - This composite endpoint will be analyzed using the win ratio method. 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. The method uses pairwise comparisons for all possible active/placebo patient pairs. A 'win' represents a patient doing better based on the hierarchical comparison. The win ratio is the total number of 'winners' divided by the total number of 'losers' in the active group.
Timepoint [2] 0 0
Up to Month 12
Secondary outcome [3] 0 0
Composite Endpoint of All-Cause Mortality and Frequency of All-Cause Hospitalizations and Urgent HF Visits - 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.
Timepoint [3] 0 0
Up to Month 12

Eligibility
Key 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
Minimum age
18 Years
Maximum age
85 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Clinical Trial Site - Westmead
Recruitment hospital [2] 0 0
Clinical Trial Site - Woolloongabba
Recruitment postcode(s) [1] 0 0
- Westmead
Recruitment postcode(s) [2] 0 0
- Woolloongabba
Recruitment outside Australia
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United States of America
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California
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Illinois
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Tennessee
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Buenos Aires
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Córdoba
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Rosario
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Santa Fe
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Aalst
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Hasselt
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Liège
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Roeselare
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Chile
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Santiago
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Brno
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Prague
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Stockton-on-Tees

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Alnylam Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to evaluate the efficacy and safety of patisiran in participants
with ATTR amyloidosis with cardiomyopathy.
Trial website
https://clinicaltrials.gov/show/NCT03997383
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Alnylam Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Alnylam Clinical Trial Information Line
Address 0 0
Country 0 0
Phone 0 0
1-877-ALNYLAM
Fax 0 0
Email 0 0
clinicaltrials@alnylam.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03997383