Eidos AG10-301 (ATTRIBUTE-CM)

A phase 3 randomised international study of the efficacy and safety of AG-10 in patients with symptomatic ATTR amyloidosis affecting the heart. Patients have hereditary or wild type ATTR amyloidosis.

Recruitment is now complete.

AG10 is a new selective TTR stabiliser drug being developed to treat ATTR amyloidosis. Destabilisation, misfolding and aggregation of TTR leads to ATTR amyloid tissue deposits. Several small molecules have been shown to bind to and stabilise TTR, potentially preventing the initiating event in ATTR amyloidogenesis. AG10 is a highly selective, potent TTR stabiliser hoped to halt or slow ATTR disease progression.

What the study involves for patients

Eligible patients were randomised in a 2:1 ratio to receive AG10 or matching placebo twice a day. Treatment will continue for a duration of about 32 months, including up to 35 days for screening, 30 months for treatment and up to 1 month for follow up. At the end of 12 months of treatment, treatment efficacy will be assessed using the 6-minute walk test and standardised questionnaires to evaluate health-related quality of life. At the end of 30 months treatment efficacy will be further assessed by analysis of all-cause mortality and frequency of hospitalisation related to cardiac causes. All patients completing the trial may be eligible for participation in an open label extension study of long term AG10 treatment.

Who can take part in the trial

Patients diagnosed with either hereditary ATTR amyloidosis or wild-type ATTR amyloidosis affecting the heart were eligible to participate in the trial. For a full list of exclusion criteria, see the www.clinicaltrials.gov website.

Outcomes

The primary outcomes assessed will be:

  • 6-minute walk test: Change from baseline to Month 12 of treatment in the total distance walked in 6 minutes.
  • Total number of deaths due to all causes and frequency of cardiovascular-related hospitalisation over 30 months.

Other outcomes assessed will include:

  • Scores on standardised health-related quality of life questionnaires (Kansas City Cardiomyopathy Questionnaire (KCCQ)) at month 12 and month 30.
  • Incidence of adverse events related to treatment.
  • Pharmacodynamics assessments of TTR stabilisation at various time points.
  • Effect of AG10 on cardiac biomarkers.
  • AG10 activity across various TTR mutations.

Timing

This study has completed recruitment and is ongoing at the NAC. We are the top recruiter globally.