An innovative phase 2 chronic pain master protocol design to assess novel mechanisms in multiple pain types

Abstract

Abstract. Introduction:. The phase 2 chronic pain master protocol (CPMP) presented here provides a construct to accelerate the investigation of novel analgesics, broadly referred to here as mechanisms. Designed to address historical challenges in analgesic research and development, such as the choice of indication, this protocol enables the efficient evaluation of potential therapeutics with different mechanisms of action in 3 pain types: nociceptive pain (osteoarthritis), neuropathic pain (diabetic peripheral neuropathic pain), and mixed pain (chronic low back pain). Methods:. The study design was determined before the identification of any specific molecule. Statistical simulations were conducted to optimize the methodology and design, the culmination of which were submitted to and accepted by the Complex Innovative Trial Design Pilot Meeting Program, a unique collaboration with the United States Food and Drug Administration. Benefits of the CPMP include limiting the number of study participants exposed to placebo and reducing the total sample size over time by leveraging placebo data across studies within a pain type and efficacy data across pain types for a specific molecule. The CPMP design enables: (1) efficient evaluation of multiple novel mechanisms of action; (2) the study of multiple molecules simultaneously or serially; (3) direct statistical comparison of molecules within a pain type; and (4) efficient planning and conduct of clinical studies. ClinicalTrials.gov ID NCT05986292. Perspective:. By evaluating novel mechanisms across different pain types, therapeutic potential can be assessed more efficiently compared with traditional individual clinical studies.