Background & Aims

Complex pathophysiology makes treatment of chronic pain and design of clinical trials for new analgesics challenging. Inadequate proof of concept (POC) study designs may contribute to the lack of new analgesics despite the high unmet medical need [1]. Due to the complexity of pain types, a singular POC clinical trial with one pain type to study intervention may not be optimal. Instead, clinical evaluation of novel analgesic mechanisms in multiple pain types provides a more comprehensive evaluation of a target’s potential. The Phase 2 Chronic Pain Master Protocol (CPMP; H0P-MC-CPMP) was designed to efficiently and flexibly facilitate simultaneous study of multiple novel interventions in osteoarthritis (OA) knee pain, chronic low back pain (CLBP), and diabetic peripheral neuropathic pain (DPNP) following the concepts of a platform trial design [2]. Here we provide baseline demographics of participants screened in CPMP and randomized to an Intervention Specific Appendix (ISA).

Methods

The CPMP is a US, multicenter, randomized, double-blind, placebo-controlled phase 2 POC trial assessing safety and efficacy of potential novel chronic pain medicines in patients with OA, CLBP, and DPNP. The CPMP is 3-tiered, including the master protocol, outlining entry criteria, randomization schema, duration, primary endpoint, and overarching procedures; the Disease State Addendum (DSA), outlining elements specific to the target population and any unique assessments to be conducted; and the ISA, addressing elements specific to the intervention under study. Each DSA can be conducted with multiple therapeutic assets via ISAs. Key inclusion criteria include visual analog scale pain value ?40 and <95 prior to randomization with a history of daily pain for at least 12 weeks and a value of ?30 on the pain catastrophizing scale. The primary objective is efficacy of each study intervention versus placebo measured as reduction in average pain intensity.

Results

4513 participants were screened for inclusion from June 2020 to May 2023. 3001 (66%) participants were screen failures, most of whom were White (70.5%) males (50.8%) with a mean (standard deviation, SD) age of 59.4 (12.1) years. 1512 participants were enrolled/randomized into 12 ISAs, most of whom were White (80.6%) females (55.6%) with a mean (SD) age of 59.7 (11.5) years.
For OA, CLBP, and DPNP subgroups, 588 (19.6%), 570 (19.0%) and 677 (22.6%) participants were screen failures, respectively, most were White (73.0%, 71.2%, and 74.4%) with mean (SD) ages of 62.2 (9.9), 55.5 (14.9), and 61.7 (10.6). Although OA was mostly females (58.5%), CLBP and DPNP were mostly males (50.9% and 61.0% respectively). 554, 530, and 433 participants were enrolled/randomized, respectively, most were White (81.2%, 78.7%, and 82.2%) with mean (SD) ages of 62.8 (8.8), 54.0 (13.4), and 62.9 (8.9), respectively. Although OA and CLBP were mostly females (61.7% and 60.6%), DPNP was mostly males (58.4%).

Conclusions

Overall, the participants that were CPMP screen failures were demographically similar to those that were enrolled/randomized. There were fewer White participants screen-failed than randomized. Similarly, although the average ages were similar between the screen failure and randomized participants, fewer White participants were screen failures in the OA, CLBP, and DPNP subgroups, compared to those enrolled/randomized. Although the genders were similar in OA and DPNP screen failed groups, there were fewer screen failed females in the CLBP subgroup.
The CPMP design offers flexibility to continually add different assets at different time points across different patient populations. Additionally, it enables efficient use of multiple promising targets across multiple pain disease states. To date, 12 ISAs have been conducted under the CPMP enrolling over 1500 distinct participants, demonstrating that this innovative design is implementable in patients suffering from chronic pain.

References

1.Hewitt, D.J., et al., Challenges in analgesic drug development. Clin Pharmacol Ther, 2009. 86(4): p. 447-50.
2.Woodcock, J. and L.M. LaVange, Master Protocols to Study Multiple Therapies, Multiple Diseases, or Both. N Engl J Med, 2017. 377(1): p. 62-70.

Presenting Author

Yan Dong

Poster Authors

Yan Dong

Eli Lilly and Company

Lead Author

E-mail

Marcia Mellado Lagarde

Eli Lilly and Company

Lead Author

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Judith Krikke

Eli Lilly and Company

Lead Author

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Phebe Kemmer

PhD

Eli Lilly and Company

Lead Author

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Zhangchen Zhao

Eli Lilly and Company

Lead Author

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Heather Shi Zhao

PhD

Eli Lilly and Company, Indianapolis, IN, USA

Lead Author

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Virginia Stauffer

PharmD

Eli Lilly and Company

Lead Author

E-mail

Topics

  • Trial Design