LY4100511 for Psoriasis

Recruiting at 61 trial locations

Overseen By There may be multiple sites in this clinical trial 1-877-CTLILLY (1-877-285-4559) or

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: DICE Therapeutics, Inc., a wholly owned subsidiary of Eli Lilly and Company

Must not be taking: Corticosteroids, Immunosuppressants, Biologics

Disqualifiers: Psoriatic arthritis, Inflammatory conditions, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

220 Participants Needed

Trial Summary

What is the purpose of this trial?

The main purpose of this study is to assess the safety and efficacy of LY4100511 in adult participants with moderate-to-severe plaque psoriasis.

Will I have to stop taking my current medications?

Yes, you must stop using topical and/or systemic therapies for psoriasis before starting the study treatment.

How does the drug LY4100511 differ from other psoriasis treatments?

LY4100511, also known as DC-853, is unique because it may target specific immune pathways involved in psoriasis, potentially offering a novel approach compared to traditional treatments that often focus on broad immunosuppression. This could mean fewer side effects and a more targeted action against the disease. ^{1 2 3 4 5}

Research Team

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Eligibility Criteria

This trial is for adults with moderate-to-severe plaque psoriasis. Specific eligibility criteria are not provided, but typically participants must meet certain health standards and may be excluded based on other medical conditions or treatments.

Inclusion Criteria

I agree to avoid sun exposure and not use tanning devices during the study.

Must have a body mass index (BMI) of 18 to 40 kilogram/square meter (kg/m2) (inclusive)

I have been diagnosed with plaque psoriasis for at least 6 months.

Exclusion Criteria

I am being treated with drugs that affect my immune system for psoriatic arthritis.

I have a history of severe psoriasis.

I have a condition like psoriasis or psoriatic arthritis, but not conditions like rheumatoid arthritis or lupus.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive LY4100511 or placebo orally for the treatment of moderate-to-severe plaque psoriasis

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• LY4100511

Trial Overview The study is testing the safety and effectiveness of a new medication called LY4100511 compared to a placebo in treating plaque psoriasis. This phase 2 trial will help determine the appropriate dose range for future studies.

Participant Groups

Group I: LY4100511 Dose 3 Experimental Treatment 1 Intervention

Participants will receive LY4100511 orally.

Group II: LY4100511 Dose 2 Experimental Treatment 1 Intervention

Participants will receive LY4100511 orally.

Group III: LY4100511 Dose 1 Experimental Treatment 1 Intervention

Participants will receive LY4100511 orally.

Group IV: Placebo Placebo Group 1 Intervention

Placebo administered orally.

Who Is Running the Clinical Trial?

DICE Therapeutics, Inc., a wholly owned subsidiary of Eli Lilly and Company

Lead Sponsor

Trials

10

Recruited

810+

Findings from Research

In a study using slc15a4feeble mice, which have unresponsive plasmacytoid dendritic cells (pDC), treatment with the TLR7-agonist imiquimod (IMQ) resulted in significantly reduced skin thickening compared to wildtype mice, indicating that pDC play a crucial role in the inflammatory response in psoriasis.

The absence of slc15a4 led to a marked reduction in systemic IFN-I induction and a blunted inflammatory response, suggesting that targeting pDC function could be a potential therapeutic strategy for managing psoriasis-related inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A requirement for slc15a4 in imiquimod-induced systemic inflammation and psoriasiform inflammation in mice. Griffith, AD., Zaidi, AK., Pietro, A., et al.[2019]

In a study involving 15 patients with severe psoriasis, the topical application of the macrolide SDZ 281-240 resulted in significant improvement of psoriatic lesions within 10 days, demonstrating its potential as an effective local treatment.

Biopsies confirmed that SDZ 281-240 reversed the histopathological and immunopathological features of psoriasis, indicating that it effectively suppresses the underlying immune response without affecting keratinocyte proliferation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clearing of psoriasis by a novel immunosuppressive macrolide. Rappersberger, K., Meingassner, JG., Fialla, R., et al.[2019]

The study identified a significant increase of FLT3(+) CD11c(+) dendritic cells in psoriatic lesions, suggesting their role in psoriasis pathology and highlighting a potential target for treatment.

The FLT3 inhibitor SKLB4771 effectively treated psoriasis-like symptoms in mice, almost completely curing the condition without noticeable toxicity, indicating a promising new therapeutic strategy that targets dendritic cells rather than T cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accumulation of FLT3(+) CD11c (+) dendritic cells in psoriatic lesions and the anti-psoriatic effect of a selective FLT3 inhibitor. Yan, HX., Li, WW., Zhang, Y., et al.[2021]

FXYD3 is significantly increased in the skin of psoriasis patients and contributes to the disease by enhancing IL-17A signaling in keratinocytes, which promotes inflammation and skin lesions.

Deleting FXYD3 in keratinocytes reduced psoriasis-like symptoms in a mouse model, suggesting that targeting FXYD3 could be a promising therapeutic strategy for treating psoriasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FXYD3 enhances IL-17A signaling to promote psoriasis by competitively binding TRAF3 in keratinocytes. Yang, W., He, R., Qu, H., et al.[2023]

In a mouse model of psoriasis, the Notch1/Hes1-PTEN/AKT/IL-17A feedback loop was found to regulate Th17 cell differentiation, which is crucial for the development of psoriasis.

Treatment with the PI3K/AKT inhibitor LY294002 significantly reduced psoriasis-like skin inflammation and reversed the increased Th17 cell activity, suggesting that targeting this feedback loop could be a promising therapeutic strategy for managing psoriatic inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Notch1/Hes1‑PTEN/AKT/IL‑17A feedback loop regulates Th17 cell differentiation in mouse psoriasis‑like skin inflammation. Lin, YW., Li, XX., Fu, FH., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

A requirement for slc15a4 in imiquimod-induced systemic inflammation and psoriasiform inflammation in mice. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Clearing of psoriasis by a novel immunosuppressive macrolide. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Accumulation of FLT3(+) CD11c (+) dendritic cells in psoriatic lesions and the anti-psoriatic effect of a selective FLT3 inhibitor. [2021]

4. China pubmed.ncbi.nlm.nih.gov

FXYD3 enhances IL-17A signaling to promote psoriasis by competitively binding TRAF3 in keratinocytes. [2023]

5. Greece pubmed.ncbi.nlm.nih.gov

Notch1/Hes1‑PTEN/AKT/IL‑17A feedback loop regulates Th17 cell differentiation in mouse psoriasis‑like skin inflammation. [2022]