A Futility Trial of Sirolimus in Multiple System Atrophy

Summary

Single-center, randomized, placebo-controlled, phase-II, futility clinical trial to determine if oral sirolimus is of sufficient promise to slow disease progression in MSA, prior to embarking on a large-scale and costly phase III study to assess its efficacy. A futility design under the null hypothesis assumes that sirolimus will slow the progression of the disease, whereas the alternative hypothesis assumes no benefit of sirolimus. If the null hypothesis is rejected (i.e., futility of sirolimus to slow progression of MSA), a major phase III study will be discouraged, whereas non-futility will offer strong support for a phase III trial to detect clinical efficacy.

Timeline

Start

2018-09-01

Primary completion

2020-11-20

Completion

2021-01-01

Outcome

Missed primary endpoint

Stopped: “Interim analysis showed early evidence of futility of sirolimus. Trial stopped per DSMB recommendation.”

paper There was no difference in change from baseline to week 48 between the sirolimus and placebo in UMSARS total score PMID 35040506 ↗

paper UMSARS total score (mean difference, 2.66; 95% CI, -7.35-6.91; P = 0.648). PMID 35040506 ↗

Publications

• Palma JA, Martinez J, Millar Vernetti P, Ma T, Perez MA, Zhong J, Qian Y, Dutta S, Maina KN, Siddique I, Bitan G, Ades-Aron B, Shepherd TM, Kang UJ, Kaufmann H. mTOR Inhibition with Sirolimus in Multiple System Atrophy: A Randomized, Double-Blind, Placebo-Controlled Futility Trial and 1-Year Biomarker Longitudinal Analysis. Mov Disord. 2022 Apr;37(4):778-789. doi: 10.1002/mds.28923. Epub 2022 Jan 18.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Sirolimus	Small molecule	2 mg	Oral
Subject	Sirolimus	Small molecule	6 mg	Oral

Indications