Moleculin Biotech, Inc. has announced Institutional Review Board (IRB) approval for its Phase 3 pivotal trial protocol, known as the MIRACLE trial, evaluating Annamycin in combination with cytarabine (AnnAraC) for patients with relapsed or refractory acute myeloid leukemia (R/R AML). The company anticipates commencing enrollment in the first quarter of 2025.
The MIRACLE trial (Moleculin R/R AML AnnAraC Clinical Evaluation) is designed as a global, adaptive Phase 3 study. The trial will include sites in the US. The study aims to assess the efficacy and safety of Annamycin in combination with cytarabine, addressing a critical unmet need in patients with R/R AML.
Adaptive Trial Design
The MIRACLE study will initially utilize an adaptive design. The first 75 to 90 subjects will be randomized in Part A of the trial to receive high-dose cytarabine (HiDAC) combined with either placebo, 190 mg/m2 of Annamycin, or 230 mg/m2 of Annamycin. These doses were specifically recommended by the FDA during an end-of-Phase 1B/2 meeting. Following this initial phase, the trial will be unblinded to select the optimal dose of Annamycin for Part B of the trial. Approximately 240 additional subjects will then be 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 the overall balance of safety, pharmacokinetics, and efficacy, aligning with the FDA's Project Optimus initiative.
Regulatory Designations and Clinical Context
Annamycin has been granted Fast Track Status and Orphan Drug Designation by the FDA for the treatment of relapsed or refractory AML, as well as Orphan Drug Designation for soft tissue sarcoma. The European Medicines Agency (EMA) has also granted Annamycin Orphan Drug Designation for relapsed or refractory AML.
Walter Klemp, Chairman and CEO of Moleculin, stated, "IRB approval marks an important milestone towards the launch of our MIRACLE pivotal Phase 3 trial of Annamycin in AML patients... The positive feedback from the clinicians on the strength of our data generated to date, along with our alignment with FDA on the strategic design of the MIRACLE study, gives us a high level of confidence as we take these next steps toward potentially bringing a much needed solution to AML patients."
About Annamycin
Annamycin is a next-generation anthracycline designed to overcome multidrug resistance mechanisms and avoid the cardiotoxicity commonly associated with currently prescribed anthracyclines. Moleculin Biotech is also developing WP1066, an Immune/Transcription Modulator, and a portfolio of antimetabolites, including WP1122, for potential treatment of pathogenic viruses and certain cancer indications.
