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

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

Transthyretin Amyloidosis (ATTR)

Transthyretin Amyloidosis (ATTR) With Cardiomyopathy

Patisiran

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)

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.

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.

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.

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.

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.

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.

Placebo

ONPATTRO

ALN-TTR02

Clinical Trial Site

Deaths and adverse events collected during the double-blind treatment period were reported. Open-label extension (OLE) period of the study is ongoing and the results will be posted after study completion. In all-cause mortality, all deaths occurred in study due to any cause are reported.

Participants were administered placebo IV every 3 weeks during the 12-month double-blind (DB) treatment period.

Double-blind Period: Placebo

Participants were administered patisiran 0.3 mg/kg intravenously (IV) every 3 weeks during the 12-month DB treatment period.

Double-blind Period: Patisiran

Participants who received placebo in DB period will be administered patisiran 0.3 mg/kg IV every 3 weeks during the 36-month open label extension (OLE) period.

Open Label Extension Period: Placebo (in DB Period) to Patisiran

Participants who received patisiran in DB period will be administered patisiran 0.3 mg/kg IV every 3 weeks during the 36-month OLE period.

Open Label Extension Period: Patisiran (in DB Period) to Patisiran

Participants were administered placebo IV every 3 weeks during the 12-month double-blind (DB) treatment period. Participants will be administered patisiran 0.3 mg/kg IV every 3 weeks during the 36-month open label extension (OLE) period.

Placebo (DB)/Patisiran (OLE)

Participants were administered patisiran 0.3 mg/kg intravenously (IV) every 3 weeks during the 12-month DB treatment period. Participants will be administered patisiran 0.3 mg/kg IV every 3 weeks during the 36-month OLE period.

Patisiran (DB+OLE)

Total

Age, Continuous

Sex: Female, Male

Asian

Black or African American

White

Other

Not Reported

Race/Ethnicity, Customized

Hispanic or Latino

Not Hispanic or Latino

Unknown

6 Minute Walk Test (6MWT)

Safety Analysis Set (SAS): All randomized participants who received any amount of study drug. Participants were summarized according to the treatment actually received.

Chief Medical Officer

Full Analysis Set: All randomized participants who received any amount of study drug. Participants were analyzed according to the treatment to which they were randomized.

Change From Baseline at Month 12 in Six-Minute Walk Test (6-MWT)

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.

Full Analysis Set: All randomized participants who received any amount of study drug. Participants were analyzed according to the treatment to which they were randomized. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis at the specified timepoint.

Change From Baseline at Month 12 in Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) Score

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.

Participants from either the placebo or patisiran groups in DB period who were receiving treatment with tafamidis at Baseline.

Baseline Tafamidis

Participants from either the placebo or patisiran groups in DB period who were not receiving treatment with tafamidis at Baseline.

No Baseline Tafamidis

Participants from the Full Analysis Set (all randomized participants who received any amount of study drug (either placebo or patisiran), grouped based on their use of tafamidis at Baseline as pre-specified in the study protocol.

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 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.

Participants from the placebo and the patisiran group in DB period who were not receiving treatment with tafamidis at Baseline.

Participants from the Full Analysis Set \[all randomized participants who received any amount of study drug (placebo or patisiran)\] and were not receiving tafamidis at Baseline were included in the data analysis for the outcome measure as pre-specified in the study protocol.

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 was compared between treatment groups using a modified Andersen-Gill model. A hazard ratio \<1 represents a favorable outcome for patisiran.

Participants were administered placebo or patisiran IV every 3 weeks during the 12-month double-blind (DB) treatment period. Participants will be administered patisiran 0.3 mg/kg IV every 3 weeks during the 36-month open label extension (OLE) period.

All Participants

All the participants from the Full Analysis Set \[all randomized participants who received any amount of study drug (either placebo or patisiran)\] were included in the data analysis for the outcome measure as pre-specified in the study protocol.

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

About this trial

Study ID

Status

Type

Phase

Placebo

Accepting

Trial Timing

What is this trial about?

What are the participation requirements?

Study Documents