Athersys has announced planned amendments to its MASTERS-2 clinical trial protocol following a Type B meeting with the US Food and Drug Administration (FDA). Held on 21 March, the meeting addressed Athersys’ proposed modifications that seek to establish primary and secondary endpoints that the company believes “best reflect the full potential benefit” of its neuroprotective MultiStem (invimestrocel) treatment for patients with acute, moderate-to-severe ischaemic stroke, as well as the evolving standard of care.
Following a meeting of leading stroke experts, regulatory specialists and statisticians—convened by Athersys in November 2022 to discuss potential changes—the company proposed four modifications to its ongoing pivotal Phase 3 MASTERS-2 trial protocol, all of which have now been accepted by the FDA. After finalising agreements around the statistical approach, Athersys will implement the following amendments to the MASTERS-2 protocol:
- Changing the timing of the primary endpoint assessed by shift analysis in modified Rankin Scale (mRS) score to day 365 (from day 90 previously)
- Retaining shift analysis in mRS score at day 90 as a key secondary endpoint, along with other revised secondary endpoints
- Removing eligibility caps on concomitant reperfusion therapy to ensure the final study population is reflective of current standard of care in the population eligible for this therapy
- Possibly electing to have an independent statistician conduct an interim analysis to assess potential sample size adjustment. MASTERS-2 currently plans to enrol 300 patients and enrolment, as previously communicated, is >50% complete
“The MASTERS-2 clinical trial protocol changes agreed to by the FDA reflect what we have learned from the completed MultiStem Phase 2 MASTERS-1 trial and the TREASURE clinical trial run in Japan by our partner Healios, as well as the significant evolution of standard of care in treating acute ischemic stroke,” said Athersys CEO Dan Camardo. “We appreciate the FDA’s guidance, which we believe ultimately will benefit stroke patients worldwide. We view the outcome of our meeting as the best-case scenario. Although changing the primary endpoint to day 365 extends the duration of MASTERS-2, we believe our accepted modifications enable accelerated patient enrolment and provide a higher conviction for demonstrating treatment potential.”
Athersys was previously granted regenerative medicine advanced therapy (RMAT), fast-track designation and special protocol assessment (SPA) agreement for the use of MultiStem in the treatment of ischaemic stroke. These designations enable sponsors to work closely with the FDA and receive guidance on expediting advancement of designated programmes, a company press release details.