Treatment of Symptomatic ATTR Cardiomyopathy (ATTRIBUTE-CM)
Research type
Research Study
Full title
A Phase 3, Randomized, Double-Blind, Placebo-controlled Study of the Efficacy and Safety of AG10 in Subjects with Symptomatic Transthyretin Amyloid Cardiomyopathy (ATTRIBUTE-CM Trial)
IRAS ID
245952
Contact name
Medical Information
Contact email
Sponsor organisation
Eidos Therapeutics
Eudract number
2018-004280-32
Duration of Study in the UK
5 years, 1 months, 30 days
Research summary
Research Summary
Transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM) is a serious, progressive, and life-threatening disease characterised by progressive left and right heart failure. Deposition of amyloid derived from either mutant or wild type TTR causes severe organ damage and dysfunction. This prospective, randomised, double-blind, parallel-group, multi-centre clinical trial will evaluate the efficacy and safety of AG10 compared to placebo, administered on a background of stable heart failure therapy, in symptomatic subjects who have an established diagnosis of ATTR-CM with either wild-type TTR or mutant TTR. 510 subjects will be enrolled in the study, randomised in a 2:1 ratio i.e. 340 subjects will receive 800 mg AG10 orally BID and 170 will receive matching placebo. Randomisation will be stratified by genotype wild-type ATTR-CM (ATTRwt-CM), or mutant ATTR-CM (ATTRm-CM) with a targeted minimum of 20% of subjects with ATTRm-CM. Randomisation will also be stratified by NT-proBNP level and renal function (eGFR). The blinded treatment phase will last 30 months. Subjects will attend their first on-treatment visit at the study site 4 weeks after baseline and then every 3 months. Subjects will undergo various assessments at each visit. In addition, monthly phone visits will be conducted in order to monitor adverse events, concomitant medications and compliance. The primary endpoints are change in six-minute walk test (6MWT) distance at month 12 and all-cause mortality and cardiovascular (CV) hospitalisation at month 30. Up to 50 participants will be invited to enroll in a cardiac MRI substudy. All subjects who complete the double-blind treatment period may be eligible to participate in an open label extension (OLE) study of long-term AG10 treatment.
Summary of results
The average age of participants taking part in the study was 77 years. Nearly all were 65 years or older (96.6%). Most were male (90.8%), white (87.9%), and recently diagnosed with ATTR-CM. About 10% of the study participants carried the variant TTR gene.
The results of the study showed that there was a beneficial effect in participants taking acoramidis compared with those participants who took placebo. This was based on the measurements the researchers had taken throughout the study that looked at deaths, hospital stays for heart problems, measures of levels of NT-proBNP, and distance walked in 6 minutes. Based on these measures, the results showed that those who had taken acoramidis had a higher chance (77.2%) of obtaining a benefit compared with those who took the placebo.
The results at the end of the study included:
* Looking at the data of those participants that had died during the study of any cause, acoramidis treatment was associated with a reduction (25%) in risk of death by any cause.* Looking at the data of those participants that visited hospital due to heart related
problems during the study, a reduction (50%) in the annual number of visits to the hospital for those participants who took acoramidis was found.* When the deaths and hospital visits for heart-related problems were analyzed together, the researchers found that the treatment benefit in the group receiving acoramidis was observed as early as 3 months after starting treatment and continued until Month 30.
* The participants treated with acoramidis were able to walk on average approximately 40 metres more than those who took placebo, a clinically meaningful difference.
* Participants treated with acoramidis had a better effect than placebo on quality of life.
* Participants treated with acoramidis had a better effect than placebo on blood levels of NT-proBNP.
Researchers look at the results of many studies to decide which drugs work well and are safe for participants. It takes participants in many studies all around the world to advance medical science. The results from this study may be different than other studies that researchers review.
REC name
Wales REC 1
REC reference
19/WA/0102
Date of REC Opinion
10 May 2019
REC opinion
Further Information Favourable Opinion