LY3526318 / Eli Lilly - LARVOL DELTA

Preclinical and clinical evaluation of a novel TRPA1 antagonist LY3526318. (PubMed, Pain) - "Adverse events were transient and mild across all phase 1 studies. In summary, LY3526318 blocked TRPA1 in vitro and in vivo, inhibited behavioral signs of enhanced nociception in animal models, and was safe and well tolerated in phase 1 clinical studies, with LY3526318-SDD displaying an appropriate pharmacokinetic profile to advance to proof-of-concept studies in patients with chronic pain."

Journal • Preclinical • Immunology • Pain

Clinical proof-of-concept results with a novel TRPA1 antagonist (LY3526318) in 3 chronic pain states. (PubMed, Pain) - "No other safety signals were identified. LY3526318 showed potential for different responses among chronic pain indications and patient subpopulations, highlighting challenges in developing TRPA1 antagonists but supporting their value as a target in managing chronic pain."

Journal • Back Pain • Diabetic Neuropathy • Hepatology • Immunology • Lumbar Back Pain • Musculoskeletal Pain • Neuralgia • Osteoarthritis • Pain • Peripheral Neuropathic Pain • Rheumatology

Central TRPA1 Inhibition is Superior to Peripheral in Alleviating DPN and OA Pain in Rats (IASP 2024) - "Orally administered Pregabalin was used as a model reference compound in both models. Central TRPA1 inhibition reversed the STZ -induced mechanical hypersensitivity whereas peripheral inhibition did not. OA pain treatments can only reduce the pain with about 20%. Interestingly, our central TRPA1 inhibitor alleviated mechanical hypersensitivity with about ?15% in 60% of rats with chronic joint pain."

Preclinical • Diabetes • Diabetic Neuropathy • Immunology • Metabolic Disorders • Musculoskeletal Diseases • Musculoskeletal Pain • Neuralgia • Orthopedics • Pain • TRPA1

Operational Benefits of the Chronic Pain Master Protocol Platform Trial (IASP 2024) - "It assessed safety and efficacy of 4 potential novel chronic pain interventions (LY3016859 Epiregulin/TGF? monoclonal antibody, LY3526318 transient receptor potential ankyrin 1 antagonist, LY3556050 somatostatin receptor 4 antagonist and LY3857210 purinergic 2X7 antagonist) vs placebo in patients with osteoarthritis of the knee, chronic low back pain and diabetic peripheral neuropathic pain... The CPMP design enables efficient testing of multiple investigational interventions across a variety of pain types while allowing study interventions to be added at different time points across patient populations. At the same time, the use of standardized design elements and dedicated resources within the overall context of this flexible design resulted in reduced enrollment timelines and operational efficiencies at several levels."

Clinical • Back Pain • Diabetic Neuropathy • Immunology • Lumbar Back Pain • Musculoskeletal Pain • Neuralgia • Osteoarthritis • Pain • Peripheral Neuropathic Pain • Rheumatology • EREG • SSTR

CPMP: A Master Protocol Study (LY900028) of Multiple Intervention-Specific-Appendices (ISAs) in Participants With Chronic Pain (clinicaltrials.gov) - P2 | N=10000 | Recruiting | Sponsor: Eli Lilly and Company

New P2 trial • Back Pain • Diabetic Neuropathy • Immunology • Lumbar Back Pain • Musculoskeletal Pain • Neuralgia • Osteoarthritis • Pain • Rheumatology

TRPA1 antagonist LY3526318 inhibits the cinnamaldehyde-evoked dermal blood flow increase: translational proof of pharmacology. (PubMed, Clin Pharmacol Ther) - "Exposure-response relationships suggest that a greater magnitude response may be observed in humans if higher antagonist concentrations could be achieved. Taken together, these results demonstrate that cinnamaldehyde-evoked changes in dermal blood flow can be utilized as a target engagement biomarker for TRPA1 activity and that LY3526318 antagonizes the ion channel both in rats and humans."

Journal • Pain

A Study of LY3526318 in Healthy Male Japanese Participants (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: Eli Lilly and Company | N=34 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal

Chronic Pain Master Protocol (CPMP): A Study of LY3526318 in Participants With Diabetic Peripheral Neuropathic Pain (clinicaltrials.gov) - P2 | N=155 | Completed | Sponsor: Eli Lilly and Company | Recruiting ➔ Completed

Trial completion • Diabetic Neuropathy • Neuralgia • Pain • Peripheral Neuropathic Pain

A Study of LY3526318 in Healthy Male Japanese Participants (clinicaltrials.gov) - P1 | N=34 | Not yet recruiting | Sponsor: Eli Lilly and Company

New P1 trial

Chronic Pain Master Protocol (CPMP): A Study of LY3526318 in Participants With Osteoarthritis (clinicaltrials.gov) - P2 | N=160 | Completed | Sponsor: Eli Lilly and Company | Active, not recruiting ➔ Completed

Trial completion • Immunology • Osteoarthritis • Pain • Rheumatology

Chronic Pain Master Protocol (CPMP): A Study of LY3526318 in Participants With Chronic Low Back Pain (clinicaltrials.gov) - P2 | N=159 | Completed | Sponsor: Eli Lilly and Company | Recruiting ➔ Completed

Trial completion • Back Pain • Lumbar Back Pain • Musculoskeletal Pain • Pain

Chronic Pain Master Protocol (CPMP): A Study of LY3526318 in Participants With Osteoarthritis (clinicaltrials.gov) - P2 | N=150 | Active, not recruiting | Sponsor: Eli Lilly and Company | Recruiting ➔ Active, not recruiting

Enrollment closed • Immunology • Osteoarthritis • Pain • Rheumatology

Chronic Pain Master Protocol (CPMP): A Study of LY3526318 in Participants With Diabetic Peripheral Neuropathic Pain (clinicaltrials.gov) - P2 | N=150 | Recruiting | Sponsor: Eli Lilly and Company | Not yet recruiting ➔ Recruiting

Enrollment open • Diabetic Neuropathy • Neuralgia • Pain • Peripheral Neuropathic Pain

Chronic Pain Master Protocol (CPMP): A Study of LY3526318 in Participants With Diabetic Peripheral Neuropathic Pain (clinicaltrials.gov) - P2; N=150; Not yet recruiting; Sponsor: Eli Lilly and Company

Clinical • New P2 trial • Diabetic Neuropathy • Neuralgia • Pain • Peripheral Neuropathic Pain

Chronic Pain Master Protocol (CPMP): A Study of LY3526318 in Participants With Chronic Low Back Pain (clinicaltrials.gov) - P2; N=150; Recruiting; Sponsor: Eli Lilly and Company; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Back Pain • Lumbar Back Pain • Musculoskeletal Pain • Pain

Chronic Pain Master Protocol (CPMP): A Study of LY3526318 in Participants With Osteoarthritis (clinicaltrials.gov) - P2; N=150; Recruiting; Sponsor: Eli Lilly and Company; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Immunology • Osteoarthritis • Pain • Rheumatology

Chronic Pain Master Protocol (CPMP): A Study of LY3526318 in Participants With Chronic Low Back Pain (clinicaltrials.gov) - P2; N=150; Not yet recruiting; Sponsor: Eli Lilly and Company

Clinical • New P2 trial • Back Pain • Lumbar Back Pain • Musculoskeletal Pain • Pain

Chronic Pain Master Protocol (CPMP): A Study of LY3526318 in Participants With Osteoarthritis (clinicaltrials.gov) - P2; N=150; Not yet recruiting; Sponsor: Eli Lilly and Company

Clinical • New P2 trial • Immunology • Osteoarthritis • Pain • Rheumatology

A Safety Study of LY3526318 in Healthy Participants (clinicaltrials.gov) - P1; N=16; Completed; Sponsor: Eli Lilly and Company; Recruiting ➔ Completed

Clinical • Trial completion

A Safety Study of LY3526318 in Healthy Participants (clinicaltrials.gov) - P1; N=16; Recruiting; Sponsor: Eli Lilly and Company; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

A Safety Study of LY3526318 in Healthy Participants (clinicaltrials.gov) - P1; N=16; Not yet recruiting; Sponsor: Eli Lilly and Company

Clinical • New P1 trial

A Study of LY3526318 in Healthy Participants (clinicaltrials.gov) - P1; N=76; Terminated; Sponsor: Eli Lilly and Company; Recruiting ➔ Terminated; COVID-19 pandemic.

Clinical • Trial termination

A Study of LY3526318 in Healthy Women (clinicaltrials.gov) - P1; N=16; Completed; Sponsor: Eli Lilly and Company; Active, not recruiting ➔ Completed

Clinical • Trial completion

A Study of LY3526318 in Healthy Women (clinicaltrials.gov) - P1; N=18; Active, not recruiting; Sponsor: Eli Lilly and Company; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

A Study of LY3526318 in Healthy Women (clinicaltrials.gov) - P1; N=18; Recruiting; Sponsor: Eli Lilly and Company; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open