Multiple Treatments for Chronic Pain

(CPMP Trial)

Recruiting at 52 trial locations

Overseen By Alan Kivitz

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Eli Lilly and Company

Disqualifiers: Heart block, Cancer, Fibromyalgia, Substance use, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

10000 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares different treatments for chronic pain, focusing on conditions like diabetic neuropathic pain, chronic back pain, and osteoarthritis. Participants will receive one of several experimental treatments (such as LY3016859 ISA, LY3526318 ISA, LY3556050 ISA, or LY3857210 ISA) or a placebo to determine which is most effective. The trial seeks individuals who have experienced daily pain for at least 12 weeks and are willing to maintain their current pain management routines without starting new treatments. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to the development of potentially effective pain management solutions.

Will I have to stop taking my current medications?

Yes, you will need to stop taking all medications for chronic pain, except for rescue medication, during the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that LY3016859, LY3526318, LY3556050, and LY3857210 are undergoing testing for chronic pain in various studies. These treatments remain in the testing phase, though some safety information is available.

A study examined LY3016859 for diabetic nerve pain, but it did not highlight specific safety details. Early trials of LY3526318 focused on tolerability, yet specific safety results were not shared.

LY3556050 targets diabetic nerve pain as well, but detailed safety information was not provided. Similarly, LY3857210 is under testing for diabetic nerve pain, with no specific safety outcomes mentioned.

These treatments are in early studies (Phase 2), indicating they have passed initial safety checks but continue to be monitored for side effects or safety issues. Although detailed safety data is unavailable, their presence in this phase suggests they are considered safe enough for further testing in people. Consulting a healthcare professional before joining a trial is essential to understand potential risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for chronic pain because they offer potentially new ways to manage conditions like osteoarthritis, diabetic neuropathic pain, and chronic back pain. Unlike standard treatments that often rely on medications like NSAIDs, opioids, or gabapentinoids, these investigational drugs—LY3016859, LY3526318, LY3556050, and LY3857210—may work through novel mechanisms that could provide pain relief with fewer side effects or reduced risk of addiction. Each of these treatments is being investigated for its unique action at the molecular level, which might offer more targeted pain management compared to traditional therapies. This could be particularly beneficial for patients who haven’t found relief with existing options.

What evidence suggests that this trial's treatments could be effective for chronic pain?

This trial will evaluate multiple treatments for chronic pain, including LY3016859, LY3526318, LY3556050, and LY3857210, each compared to a placebo. Research suggests that LY3016859, which participants in this trial may receive, might help with diabetic nerve pain by affecting proteins related to pain signals. Although promising signs exist, more evidence is needed. LY3526318 targets a part of the body involved in feeling pain and has shown some benefits compared to a placebo in early tests. LY3556050 works on specific parts of the body involved in pain, and initial results suggest it might help reduce pain. LY3857210, tested for diabetic nerve pain and chronic back pain in this trial, aims to block pain signals. While early findings are encouraging, more research is needed to confirm its effectiveness. ^{1 2 5 6 7}

Who Is on the Research Team?

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Are You a Good Fit for This Trial?

This trial is for adults with chronic pain from conditions like osteoarthritis or diabetic neuropathy, who've had daily pain for at least 12 weeks. Participants must be willing to stop all other pain meds except emergency ones, not start new therapies during the study, have a BMI under 40 kg/m², and score specific values on pain scales.

Inclusion Criteria

Your pain level, as measured on a scale, falls between 40 and 95.

Your body mass index is less than 40 kg/m².

Your score on the pain catastrophizing scale is 30 or lower.

Exclusion Criteria

You have had a problem with alcohol, illegal drugs, or pain medicines in the past 2 years.

I have not had any cancer except for skin cancer that was removed, in the last 2 years.

I have a serious heart rhythm problem.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either active intervention or matching placebo for chronic pain conditions

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• LY3016859 ISA
• LY3526318 ISA
• LY3556050 ISA
• LY3857210 ISA
• Placebo
• Placebo Oral

Trial Overview The study tests multiple interventions (LY3857210 ISA, LY3526318 ISA, etc.) against placebos to manage chronic pain. It's designed to allow each intervention-specific appendix (ISA) to begin independently as they become ready for clinical trials within an overarching protocol.

How Is the Trial Designed?

Group I: LY3857210 Osteoarthritis ISA Experimental Treatment 2 Interventions

Participants are randomized to receive either active LY3857210 or matching placebo

Group II: LY3857210 Diabetic Neuropathic Pain ISA Experimental Treatment 2 Interventions

Participants are randomized to receive either active LY3857210 or matching placebo

Group III: LY3857210 Chronic Back Pain ISA Experimental Treatment 2 Interventions

Participants are randomized to receive either active LY3857210 or matching placebo

Group IV: LY3556050 Osteoarthritis ISA Experimental Treatment 2 Interventions

Participants are randomized to receive either active LY3556050 or matching placebo

Group V: LY3556050 Diabetic Neuropathic Pain ISA Experimental Treatment 2 Interventions

Participants are randomized to receive either active LY3556050 or matching placebo

Group VI: LY3556050 Chronic Back Pain ISA Experimental Treatment 2 Interventions

Participants are randomized to receive either active LY3556050 or matching placebo

Group VII: LY3526318 Osteoarthritis ISA Experimental Treatment 2 Interventions

Participants are randomized to receive either active LY3526318 or matching placebo

Group VIII: LY3526318 Diabetic Neuropathic Pain ISA Experimental Treatment 2 Interventions

Participants are randomized to receive either active LY3526318 or matching placebo

Group IX: LY3526318 Chronic Back Pain ISA Experimental Treatment 2 Interventions

Participants are randomized to receive either active LY3526318 or matching placebo

Group X: LY3016859 Osteoarthritis ISA Experimental Treatment 2 Interventions

Participants are randomized to receive either active LY3016859 or matching placebo

Group XI: LY3016859 Diabetic Neuropathic Pain ISA Experimental Treatment 2 Interventions

Participants are randomized to receive either active LY3016859 or matching placebo

Group XII: LY3016859 Chronic Back Pain ISA Experimental Treatment 2 Interventions

Participants are randomized to receive either active LY3016859 or matching placebo

Who Is Running the Clinical Trial?

Eli Lilly and Company

Lead Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Published Research Related to This Trial

A double-blind, placebo-controlled trial involving 125 fibromyalgia patients demonstrated that milnacipran significantly improved pain, physical function, and fatigue compared to placebo, suggesting it may be an effective treatment option.

Milnacipran, a dual norepinephrine and serotonin reuptake inhibitor, was generally well tolerated at doses up to 200 mg/day, indicating a favorable safety profile for managing fibromyalgia symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Newer treatments for fibromyalgia syndrome. Harris, RE., Clauw, DJ.[2021]

In a review of 18 studies involving 3546 patients with fibromyalgia syndrome, a significant 18.6% of participants experienced a 50% reduction in pain from placebo treatments, highlighting the strong placebo effect in chronic pain trials.

The study also found that 10.9% of patients in placebo groups dropped out due to adverse events, indicating a notable nocebo effect, which suggests that both placebo and nocebo responses play a critical role in the perceived efficacy and safety of drug treatments for fibromyalgia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo and nocebo responses in randomised controlled trials of drugs applying for approval for fibromyalgia syndrome treatment: systematic review and meta-analysis. Häuser, W., Sarzi-Puttini, P., Tölle, TR., et al.[2022]

In a study involving 52 Japanese patients with chronic low back pain, the addition of open-label placebo (OLP) to standard treatment did not show superior benefits compared to standard treatment alone after 3 and 12 weeks.

Both groups experienced significant improvements in functional disability, indicating that while OLP did not enhance outcomes, standard treatment was effective in reducing disability in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-Label Placebo Trial among Japanese Patients with Chronic Low Back Pain. Ikemoto, T., Ueno, T., Arai, YC., et al.[2021]

In a study of 884 patients with fibromyalgia, milnacipran at a dose of 200 mg/day significantly improved pain and overall symptoms compared to placebo, demonstrating its efficacy in treating fibromyalgia.

Milnacipran was found to be safe and well tolerated, with common side effects including nausea, hyperhidrosis, and headache, indicating it can be a viable treatment option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A European multicenter randomized double-blind placebo-controlled monotherapy clinical trial of milnacipran in treatment of fibromyalgia. Branco, JC., Zachrisson, O., Perrot, S., et al.[2022]

In a review of 42 trials on neuropathic pain and 29 trials on low back pain, it was found that participants on placebo consumed significantly more rescue medication (RM) than those on active drugs, which could mask the true effectiveness of the treatments.

Specifically, in trials showing a small to medium effect size for the investigational drugs, placebo participants used 17% to 30% more RM, highlighting the need for better analytical methods to account for RM consumption in chronic pain studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of rescue medication in placebo-controlled trials of pharmacotherapy for neuropathic pain and low back pain. Grøvle, L., Hasvik, E., Haugen, AJ.[2023]

A systematic review of 108 randomized placebo-controlled trials involving 44,171 participants found that using an enriched study design did not significantly change the treatment effect size for pain intensity in chronic musculoskeletal pain.

However, enriched designs were associated with a reduced risk of adverse events for opioid treatments, suggesting they may enhance safety in certain analgesic trials, although this effect was not observed for other analgesics or serious adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of effect sizes between enriched and nonenriched trials of analgesics for chronic musculoskeletal pain: a systematic review. Yamato, TP., Maher, CG., Saragiotto, BT., et al.[2021]

In a study involving 237 participants (60 with osteoarthritis, 79 with fibromyalgia, and 98 healthy individuals), those with chronic pain experienced a significant reduction in pain from a placebo treatment, similar to healthy individuals.

The study found that the magnitude of placebo analgesia and the expectation of pain relief were comparable across all diagnostic groups, suggesting that individuals with chronic pain can effectively respond to placebo treatments despite their psychological challenges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Individuals with chronic pain have the same response to placebo analgesia as healthy controls in terms of magnitude and reproducibility. Power, A., Brown, CA., Sivan, M., et al.[2022]

Nabiximols demonstrated a significant reduction in chronic neuropathic pain compared to placebo, with a mean difference of -0.40 on a pain scale, based on a systematic review of nine randomized controlled trials involving 1289 participants.

The evidence quality was moderate, indicating that while nabiximols showed a small but meaningful effect, further larger studies are needed to confirm its efficacy in treating neuropathic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nabiximols in Chronic Neuropathic Pain: A Meta-Analysis of Randomized Placebo-Controlled Trials. Dykukha, I., Malessa, R., Essner, U., et al.[2021]

In a study involving knee osteoarthritis and non-radicular low back pain patients, significant placebo effects were observed, particularly in pain intensity and range of motion, indicating that the placebo response can influence both self-reported and performance-based outcomes.

The study found that gender and diagnosis affected the magnitude of placebo responses, with women in the knee osteoarthritis group showing notable improvements, suggesting that these factors should be considered in future clinical trials to better understand and potentially mitigate placebo effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

"Managing" the Placebo Effect: The Single-Blind Placebo Lead-in Response in Two Pain Models. Harden, RN., Saracoglu, M., Connolly, S., et al.[2018]

In a study involving 87 healthy volunteers, providing individuals with control over when they administer a placebo treatment significantly enhanced the effectiveness and duration of placebo analgesia compared to standard passive conditioning.

Participants with instrumental control not only experienced greater pain relief but also showed reduced anxiety responses, suggesting that giving patients control could be a simple and ethical way to improve pain management outcomes in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Instrumental Control Enhances Placebo Analgesia. Tang, B., Geers, A., Barnes, K., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05986292

NCT05986292 | A Master Protocol Study (LY900028) of ... The purpose of the chronic pain master protocol is to compare independent pain interventions and establish an overarching structure for the disease-state ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40266472/

Population Pharmacokinetics and Pharmacodynamics of ... Population Pharmacokinetics and Pharmacodynamics of Fepixnebart (LY3016859) and Epiregulin in Patients with Chronic Pain.

3. trials.lilly.com trials.lilly.com/en-US/trial/282955

A Study of LY3016859 in Participants With Diabetic Peripheral ... This study is being done to test the safety and efficacy of the study drug LY3016859 for the treatment of diabetic peripheral neuropathic pain.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04476108

NCT04476108 | Chronic Pain Master Protocol (CPMP): A ... This study is being done to test the safety and efficacy of the study drug LY3016859 for the treatment of diabetic peripheral neuropathic pain.

5. withpower.com withpower.com/trial/phase-2-neuralgia-2020-be884

Multiple Treatments for Chronic Pain (CPMP Trial) What data supports the effectiveness of the drug LY3016859 ISA and similar treatments for chronic pain? Research shows that placebo treatments can ...

6. trials.arthritis.org trials.arthritis.org/trials/NCT05986292

A Master Protocol Study (LY900028) of Multiple Intervention ... The purpose of the chronic pain master protocol is to compare independent pain interventions and establish an overarching structure for the disease-state ...

7. sigma.larvol.com sigma.larvol.com/product.php?e1=4998&tab=newstrac

fepixnebart (LY3016859) News The CPMP design enables efficient testing of multiple investigational interventions across a variety of pain types while allowing study interventions to be ...