LY3848575 for Neuropathic Pain

Not currently recruiting at 106 trial locations

Overseen By Jeffrey A Norton

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Eli Lilly and Company

Disqualifiers: Uncontrolled diabetes, Cancer, Suicidal, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 26-28 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, LY3848575 (an experimental treatment), to determine its safety and effectiveness for treating nerve pain that starts in the feet and moves up to the knees. Participants will receive one of three doses of the drug or a placebo (a substance with no active drug) for comparison. It suits those who have experienced nerve pain with a known or unknown cause for at least six months, specifically in their lower legs, and who are willing to adjust their current pain management routine. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

Yes, you will need to stop taking all medications for chronic pain conditions, except for the allowed pain medications specified by the trial.

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

Research has shown that LY3848575 underwent safety testing in earlier studies. In these studies, participants received single doses of the treatment, and researchers monitored for any side effects. This process helps determine how well the body tolerates the treatment. The trial under consideration is in Phase 2, indicating it has passed initial safety tests and is now being evaluated for effectiveness and further safety in a larger group. This phase typically provides more detailed information about side effects and their frequency. Although exact data from earlier phases aren't provided here, reaching Phase 2 suggests that LY3848575 is likely to be fairly well-tolerated, with manageable side effects. For personalized insights, discussing concerns with the trial team is recommended. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for nerve pain?

Researchers are excited about LY3848575 for treating neuropathic pain because it offers a potentially new approach compared to existing treatments like gabapentin, pregabalin, and duloxetine. Unlike these standard medications, which mainly focus on suppressing nerve signals or altering neurotransmitter levels, LY3848575 might target specific pathways involved in pain signaling in a different manner, potentially offering relief for patients who don't respond well to current therapies. Additionally, LY3848575 is administered subcutaneously, which could provide a more consistent delivery method and improved patient compliance compared to oral medications. This new approach might make LY3848575 a promising option for those seeking alternative treatments for neuropathic pain.

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

Research has shown that LY3848575, a type of antibody, can lower pain sensitivity in chronic pain models. This trial will test different doses of LY3848575 to evaluate its effectiveness in reducing nerve pain, which often starts in the feet and moves up the leg. In earlier studies, LY3848575 reduced pain symptoms. Although still under investigation, early results appear promising for those with this type of nerve pain. However, more research is needed to confirm its effectiveness in people. ^{2 3 4 5 6}

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 individuals experiencing nerve pain that starts in the feet and progresses up to just below the knee, known as painful distal sensory polyneuropathy. Participants should be able to commit to a study period of up to 30 weeks.

Inclusion Criteria

Have a Visual Analog Scale (VAS) pain value ≥40 and <95 at screening

I am willing to stop taking my current chronic pain medications, except those permitted.

Individuals NOT of childbearing potential may participate in the trial. Contraceptive use by participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies

Exclusion Criteria

I've had a procedure to permanently lose feeling in a specific area within the last 6 months.

I have had cancer within the last 2 years, except for certain skin cancers or cancers that caused nerve pain due to chemotherapy.

My diabetes hasn't been under control for 3 months and my HbA1c level is above 11.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive LY3848575 or placebo administered subcutaneously for chronic neuropathic pain

26-28 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• LY3848575

Trial Overview The trial is testing LY3848575 against a placebo to determine its safety and effectiveness in treating nerve pain associated with polyneuropathy. The duration of participation may last up to 30 weeks, including screening time.

How Is the Trial Designed?

Group I: LY3848575 Dose 3 Experimental Treatment 1 Intervention

LY3848575 high dose administered SC.

Group II: LY3848575 Dose 2 Experimental Treatment 1 Intervention

LY3848575 mid dose administered SC.

Group III: LY3848575 Dose 1 Experimental Treatment 1 Intervention

LY3848575 low dose administered subcutaneously (SC).

Group IV: Placebo Placebo Group 1 Intervention

Placebo administered SC.

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

The study found that ErbB4, a receptor activated by neuregulin-1, plays a crucial role in the development of mechanical allodynia, a common symptom of neuropathic pain, by being activated in spinal parvalbumin interneurons after nerve injury.

Knocking down ErbB4 in the spinal cord not only prevented but also reversed mechanical allodynia in mice, indicating that targeting ErbB4 could be a potential therapeutic strategy for managing neuropathic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ErbB4 in Spinal PV Interneurons Regulates Mechanical Allodynia in Neuropathic Pain via Modulation of Glycinergic Inhibitory Tone. Yu, Y., Wei, G., Zhou, Q., et al.[2022]

In a study using rat models of nerve injury, the expression of neuregulin1 (Nrg1) type I and type II isoforms significantly increased in the dorsal root ganglion (DRG) after spinal nerve ligation, indicating their potential role in nerve injury response.

Conversely, the expression of Nrg1 type III decreased in the DRG, suggesting that changes in Nrg1 isoform expression may be linked to the development of neuropathic pain following nerve injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expression changes of the neuregulin 1 isoforms in neuropathic pain model rats. Kanzaki, H., Mizobuchi, S., Obata, N., et al.[2012]

The study identified ephrinB1 as a key gene involved in lysophosphatidic acid (LPA)-induced neuropathic pain, confirmed through gene expression profiling in the dorsal root ganglion of nerve injury models.

Blocking ephrinB1 with antisense oligodeoxynucleotides significantly reduced pain responses, indicating its crucial role in pain transmission and suggesting potential therapeutic targets for neuropathic pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Profiling of BoNT/C3-reversible gene expression induced by lysophosphatidic acid: ephrinB1 gene up-regulation underlying neuropathic hyperalgesia and allodynia. Uchida, H., Matsumoto, M., Ueda, H.[2016]

A genetic marker in the EREG gene was linked to pain intensity in chronic facial pain patients, showing that a specific allele (rs6836436) was associated with lower chronic pain but higher acute facial pain.

In mouse models, blocking EREG with a monoclonal antibody reduced chronic pain sensitivity but worsened pain during acute pain development, suggesting that EREG plays a complex role in pain modulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The dichotomous role of epiregulin in pain. Verma, V., Khoury, S., Parisien, M., et al.[2022]

The new compound (S)-17 (UCM-05194) is identified as the most potent and selective agonist for the LPA1 receptor, showing significant efficacy in reducing neuropathic pain in an in vivo model.

By activating the LPA1 receptor, (S)-17 induces internalization of the receptor, leading to its functional inactivation in sensory neurons, which contributes to its ability to attenuate pain perception.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Novel Agonist of the Type 1 Lysophosphatidic Acid Receptor (LPA1), UCM-05194, Shows Efficacy in Neuropathic Pain Amelioration. González-Gil, I., Zian, D., Vázquez-Villa, H., et al.[2021]

In a phase II trial involving 77 patients with diabetic peripheral neuropathic pain, fulranumab showed a significant dose-dependent reduction in pain, particularly at the 10 mg dose compared to placebo, indicating its potential efficacy as a treatment.

The treatment was generally well tolerated, with common side effects including arthralgia, peripheral edema, and diarrhea, but no serious adverse events like joint replacement or death were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulranumab for treatment of diabetic peripheral neuropathic pain: A randomized controlled trial. Wang, H., Romano, G., Frustaci, ME., et al.[2021]

Chronic constriction injury of the trigeminal nerve in rats leads to mechanical allodynia, which is significantly delayed in transgenic rats lacking neuregulin 1, indicating its role in the development of neuropathic pain.

The ErbB2 inhibitor Lapatinib effectively alleviates mechanical allodynia in wild type rats, suggesting that targeting the Neuregulin 1-ErbB3-ErbB2 signaling pathway could be a promising strategy for treating trigeminal neuropathic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trigeminal nerve injury ErbB3/ErbB2 promotes mechanical hypersensitivity. Ma, F., Zhang, L., Westlund, KN.[2021]

In a mouse model of chronic constriction injury, the expression of EphA1 was found to increase as neuropathic pain progressed, indicating its potential role in the disease's development.

Knocking down EphA1 expression led to significant improvements in pain sensitivity and reduced inflammation, suggesting that targeting EphA1 and its associated signaling pathways could be a promising approach for treating neuropathic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EphA1 aggravates neuropathic pain by activating CXCR4/RhoA/ROCK2 pathway in mice. Li, Q., Li, R., Zhu, X., et al.[2023]

Citations

1. withpower.com withpower.com/trial/phase-2-neuralgia-9-2024-d64ae

LY3848575 for Neuropathic Pain In studies, an antibody against epiregulin reduced pain sensitivity in chronic pain models, indicating potential effectiveness for neuropathic pain. Show more ...

2. synapse.patsnap.com synapse.patsnap.com/drug/b77f9142ea554bf8bb41a3a8c33572c9

LY-3848575 - Drug Targets, Indications, Patents A Phase 1, Randomized, Double-blind, Placebo-controlled Study to Investigate Safety, Tolerability, and Pharmacokinetics With Single Intravenous Ascending Doses.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06568042

NCT06568042 | Effects of LY3848575 Versus Placebo in ... The purpose of this study is to evaluate how safe and how well a treatment works compared to placebo for people with nerve pain that begins in their feet ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12064609/

Population Pharmacokinetics and Pharmacodynamics of ... This population pharmacokinetic analysis used data from three 26-week, phase 2, proof-of-concept studies in osteoarthritis, diabetic peripheral ...

5. trial.medpath.com trial.medpath.com/clinical-trial/44f0a46e1a6c9b57/nct06568042-phase-2-study-ly3848575-chronic-neuropathic-pain

Effects of LY3848575 Versus Placebo in Participants With ... The purpose of this study is to evaluate how safe and how well a treatment works compared to placebo for people with nerve pain that begins in their feet ...

6. trials.lilly.com trials.lilly.com/en-US/trial/530315

Effects of LY3848575 Versus Placebo in Participants With ... The purpose of this study is to evaluate how safe and how well a treatment works compared to placebo for people with nerve pain that begins in their feet.