Moleculin Biotech has amended the clinical trial protocol for its Phase 3 MIRACLE trial, potentially accelerating the timeline for Annamycin in combination with cytarabine (AnnAraC) for relapsed or refractory acute myeloid leukemia (R/R AML). The amended protocol, agreed upon with the FDA, allows for earlier unblinding of preliminary data, which could expedite the drug's path to market.
The MIRACLE trial (MB-108) is a global, adaptive Phase 3 study evaluating Annamycin in combination with cytarabine for patients with R/R AML. The trial's design incorporates an adaptive component, initially randomizing the first 75 to 90 subjects to receive high-dose cytarabine (HiDAC) combined with either placebo, 190 mg/m2 of Annamycin, or 230 mg/m2 of Annamycin.
Accelerated Data Unblinding
The amended protocol allows for unblinding of preliminary primary efficacy data, specifically complete remission (CR) rates, and safety/tolerability data after the first 45 subjects are evaluated. This early unblinding will provide data on 30 subjects treated with Annamycin (at both 190mg/m2 and 230mg/m2 doses) plus HiDAC and 15 subjects treated with HiDAC alone. Moleculin anticipates reaching this 45-subject milestone in the second half of 2025. An additional unblinding of the next 30-45 subjects is planned for 2026.
Trial Design and Patient Enrollment
Part B of the trial will involve approximately 244 additional subjects randomized to receive either HiDAC plus placebo or HiDAC plus the optimal dose of Annamycin. The selection of the optimal dose will be based on safety, pharmacokinetics, and efficacy data from Part A, aligning with the FDA's Project Optimus initiative. The increase in subjects from 240 to 244 accounts for the statistical impact of the additional unblinding.
Regulatory Status and Future Steps
Annamycin holds Fast Track Status and Orphan Drug Designation from the FDA for R/R AML, as well as Orphan Drug Designation from the European Medicines Agency (EMA). The amended protocol is currently under review by the Institutional Review Board (IRB), and upon approval, will be filed with the FDA as an amendment to the Company's Initial New Drug (IND) application.
"This amended protocol enables us to share definitive data earlier, which helps to partially de-risk financing the trial and potentially accelerates the timeline for strategic partnering," said Walter Klemp, Chairman and Chief Executive Officer of Moleculin. "We believe that the unblinding of data at 45 subjects will enable us to begin assessing all three arms of the study and provide us with a clear path forward in understanding the potential of Annamycin for AML patients."
