LY3972406 for Psoriasis

Recruiting at 22 trial locations

Overseen By Malisa Agard

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Eli Lilly and Company

Disqualifiers: Other skin conditions, Active infection, Autoimmune diseases, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

75 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new medication called LY3972406 to see if it can help adults with moderate-to-severe plaque psoriasis. The goal is to find out if it works well and is safe to use. Plaque psoriasis causes red, scaly patches on the skin, and this medication aims to reduce these symptoms.

Do I need to stop my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the idea that LY3972406 for Psoriasis is an effective treatment?

The available research does not provide specific data on the effectiveness of LY3972406 for treating psoriasis. Instead, it discusses other treatments like apremilast, anti-TNF drugs, and an anti-IL-23 receptor antibody. For example, apremilast showed positive results in 41% of patients, and anti-TNF drugs were effective for some but not all patients. Without specific data on LY3972406, we cannot conclude its effectiveness for psoriasis based on the provided information. ^{1 2 3 4 5}

What safety data is available for LY3972406 (DES-7114) in treating psoriasis?

The provided research does not contain specific safety data for LY3972406, LY-3972406, or DES-7114. The studies mentioned focus on other treatments for psoriasis, such as dimethylfumarate, siplizumab, and interleukin-23 inhibitors, and their safety profiles. Therefore, no direct safety data for LY3972406 is available in the given research. ^{6 7 8 9 10}

Is the drug LY3972406 a promising treatment for psoriasis?

The information provided does not mention LY3972406, so we cannot determine if it is a promising treatment for psoriasis based on the given articles. ^{11 12 13 14 15}

Research Team

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 on - 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 who've had moderate-to-severe chronic plaque psoriasis for at least 6 months. Participants must be able to swallow pills, allow blood sampling, and agree to skin biopsies. It's not open to those with other skin conditions or autoimmune diseases, active infections, or women who are breastfeeding.

Inclusion Criteria

Agree to skin biopsies

Have venous access sufficient to allow for blood sampling

I have had severe skin psoriasis for at least 6 months.

Exclusion Criteria

I currently have or recently had a serious infection.

I have a skin condition other than plaque psoriasis.

Are lactating or breastfeeding women

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either LY3972406 or placebo to assess efficacy and safety

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• LY3972406

Trial Overview The study is testing the effectiveness and safety of a new medication called LY3972406 compared to a placebo in treating plaque psoriasis. Participants will randomly receive either the actual drug or a placebo without knowing which one they're getting.

Participant Groups

Group I: LY3972406 Dose 2 Experimental Treatment 1 Intervention

Participants will receive an oral dose of LY3972406

Group II: LY3972406 Dose 1 Experimental Treatment 1 Intervention

Participants will receive an oral dose of LY3972406

Group III: Placebo Placebo Group 1 Intervention

Participants will receive 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

Findings from Research

A study of 116 psoriasis patients found that specific gene variants in the CDKAL1 gene significantly influence the effectiveness of anti-TNF therapies, with CC homozygotes showing a higher response rate (72% vs. 45% for non-responders).

Identifying these gene variants could potentially help predict which patients will respond well to anti-TNF treatments, improving personalized treatment strategies for psoriasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CDKAL1 gene variants affect the anti-TNF response among Psoriasis patients. Coto-Segura, P., Batalla, A., González-Fernández, D., et al.[2022]

The anti-IL-23 receptor monoclonal antibody AS2762900-00 significantly reduced epidermal thickness in a psoriatic human skin xenograft model, indicating its potential efficacy in treating psoriasis by blocking IL-23 signaling pathways.

AS2762900-00 also inhibited STAT3 phosphorylation, a key downstream signal of IL-23 receptor activation, suggesting that monitoring STAT3 levels could serve as a useful biomarker for assessing the drug's effects in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AS2762900-00, a potent anti-human IL-23 receptor monoclonal antibody, prevents epidermal hyperplasia in a psoriatic human skin xenograft model. Sasaki-Iwaoka, H., Taguchi, K., Okada, Y., et al.[2019]

In a study of 34 patients with moderate-to-severe plaque psoriasis treated with apremilast for 26 weeks, 41% achieved significant improvement (delta PASI 75), indicating the drug's efficacy in managing psoriasis symptoms.

Genome-wide analysis identified specific genetic markers associated with treatment response to apremilast, suggesting that genetic profiling could help predict which patients will benefit most from this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apremilast Pharmacogenomics in Russian Patients with Moderate-to-Severe and Severe Psoriasis. Verbenko, DA., Karamova, AE., Artamonova, OG., et al.[2021]

A genome-wide association study (GWAS) involving 243 psoriasis patients treated with anti-TNF drugs aimed to identify biomarkers predicting treatment response, but only two SNPs near the NPFFR2 gene approached significance, indicating a potential link to drug efficacy.

Despite the findings, further research with larger patient cohorts is necessary to validate these SNPs as reliable biomarkers for predicting responses to anti-TNF therapies in psoriasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genome-wide association analysis of psoriasis patients treated with anti-TNF drugs. Ovejero-Benito, MC., Muñoz-Aceituno, E., Sabador, D., et al.[2021]

In a study of 478 Danish psoriasis patients, specific genetic variants were identified that could predict responses to anti-TNF treatments and ustekinumab, potentially guiding personalized treatment plans.

Variants associated with higher IL-1β levels were linked to poorer responses to both anti-TNF and ustekinumab, while variants related to higher interferon-γ levels were favorable for ustekinumab treatment, suggesting a complex relationship between genetics and treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Associations between functional polymorphisms and response to biological treatment in Danish patients with psoriasis. Loft, ND., Skov, L., Iversen, L., et al.[2019]

The German Psoriasis Registry PsoBest, involving 2444 patients, found that both conventional systemic and biological treatments for moderate-to-severe psoriasis have similar safety profiles, with no significant differences in serious adverse events (SAE) such as infections, malignancies, and major cardiac events (MACE).

The overall rate of serious adverse events was low, at 1.3 per 100 patient years for conventional drugs and 1.5 for biologics, indicating that both treatment types are safe for long-term use in routine care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug safety of systemic treatments for psoriasis: results from The German Psoriasis Registry PsoBest. Reich, K., Mrowietz, U., Radtke, MA., et al.[2018]

In a study of 81 elderly psoriatic patients treated with DMF for up to 24 weeks, significant improvements in psoriasis severity were observed, with the Psoriasis Area and Severity Index (PASI) score decreasing from a mean of 9.8 at baseline to 2.7 by week 24.

Despite 72.8% of patients reporting adverse events, including gastrointestinal issues and lymphocytopenia, DMF was generally well tolerated, suggesting it could be a viable first-line treatment for elderly patients with psoriasis, though long-term safety monitoring is essential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of dimethylfumarate in elderly psoriasis patients: a multicentric Italian study. Ricceri, F., Bardazzi, F., Buggiani, G., et al.[2022]

In a study involving 2845 patients and 8954 treatment cycles, ustekinumab and secukinumab were found to have the lowest rates of adverse events compared to other systemic drugs for psoriasis, indicating a safer profile for these treatments.

Conversely, cyclosporine and infliximab were associated with the highest rates of adverse events, suggesting that these medications may carry more risks for patients with moderate to severe psoriasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety of nine systemic medications for psoriasis: A cohort study using the Spanish Registry of Adverse Events for Biological Therapy in Dermatological Diseases (BIOBADADERM) Registry. Daudén, E., Carretero, G., Rivera, R., et al.[2021]

Siplizumab, an anti-CD2 monoclonal antibody, demonstrated an acceptable safety profile in two phase II studies involving 544 adults with plaque psoriasis, with common side effects including lymphopenia, chills, and headache, but no significant immune suppression observed.

The studies indicated that while anti-siplizumab antibodies were detected, they did not correlate with adverse events, suggesting that siplizumab could be a promising alternative therapy for psoriasis, although further testing with higher doses is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of intravenous and subcutaneous siplizumab, an anti-CD2 monoclonal antibody, for the treatment of plaque psoriasis: results of two randomized, double-blind, placebo-controlled studies. Langley, RG., Papp, K., Bissonnette, R., et al.[2019]

Real-world data analysis from the European EudraVigilance database suggests a potential association between IL-23 inhibitors (risankizumab and tildrakizumab) and the occurrence of suspected adverse reactions related to cancer in psoriasis patients.

The study indicates that the risk of oncologic adverse reactions may be higher in men compared to women, highlighting a gender disparity in the safety profile of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suspected oncologic adverse reactions associated with interleukin-23 inhibitors in EudraVigilance: Comparative study and gender distribution. Calapai, F., Mannucci, C., Cardia, L., et al.[2023]

In a study of 50 adults with moderate-to-severe psoriasis, Tofacitinib therapy for 12 weeks resulted in significant improvements in both psoriasis severity (measured by PASI) and quality of life (measured by DLQI), with p-values less than 0.001.

The most notable improvements in quality of life were observed in the areas of symptoms and feelings, daily activities, and treatment satisfaction, indicating that Tofacitinib not only reduces skin symptoms but also enhances overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Impact of Tofacitinib on Quality of Life in Patients with Moderate-to-Severe Psoriasis- An Observational Study. Mohta, A., Nyati, A., Ghiya, BC., et al.[2023]

New oral therapies for psoriasis, such as apremilast and tofacitinib, are being developed to provide patients with effective alternatives to biologics, which are preferred for their ease of use.

While these oral therapies show promise, they have limitations in efficacy and safety, highlighting the need for further research and longer clinical trials to better understand their role in treating psoriasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel Oral Therapies for Psoriasis and Psoriatic Arthritis. Yiu, ZZ., Warren, RB.[2021]

Tildrakizumab, a monoclonal antibody targeting IL-23, has shown significant efficacy in treating moderate-to-severe chronic plaque psoriasis, outperforming placebo and etanercept in clinical trials, with effects increasing up to 28 weeks and sustained efficacy for up to 3 years.

The safety profile of tildrakizumab is favorable, with good tolerability and only a slightly higher incidence of nasopharyngitis reported, indicating it is a safe option for patients with psoriasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tildrakizumab: An Evidence-Based Review of Its Use in the Treatment of Moderate-to-Severe Chronic Plaque Psoriasis. Näslund-Koch, C., Zachariae, C., Skov, L.[2020]

Guselkumab, a fully human monoclonal antibody, is an effective treatment for moderate to severe psoriasis, showing a lower cost per responder compared to most targeted therapies at week 16 and in year 1 analyses.

In terms of cost-effectiveness, guselkumab was found to be more economical than all comparators except for adalimumab and brodalumab, making it a viable option for patients in Germany.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost per responder analysis of guselkumab versus targeted therapies in the treatment of moderate to severe plaque psoriasis in Germany. Augustin, M., Wirth, D., Mahlich, J., et al.[2022]

Guselkumab has a favorable safety profile over 5 years of treatment for moderate-to-severe psoriasis, with low rates of serious adverse events such as serious infections (0.85/100 patient-years) and nonmelanoma skin cancer (0.34/100 patient-years).

Out of 1721 patients treated with guselkumab, 78.4% continued treatment through week 252, indicating good long-term adherence and effectiveness in managing psoriasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Consistent safety profile with up to 5 years of continuous treatment with guselkumab: Pooled analyses from the phase 3 VOYAGE 1 and VOYAGE 2 trials of patients with moderate-to-severe psoriasis. Blauvelt, A., Tsai, TF., Langley, RG., et al.[2022]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

CDKAL1 gene variants affect the anti-TNF response among Psoriasis patients. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

AS2762900-00, a potent anti-human IL-23 receptor monoclonal antibody, prevents epidermal hyperplasia in a psoriatic human skin xenograft model. [2019]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Apremilast Pharmacogenomics in Russian Patients with Moderate-to-Severe and Severe Psoriasis. [2021]

4. Denmark pubmed.ncbi.nlm.nih.gov

Genome-wide association analysis of psoriasis patients treated with anti-TNF drugs. [2021]

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

Associations between functional polymorphisms and response to biological treatment in Danish patients with psoriasis. [2019]

6. Germany pubmed.ncbi.nlm.nih.gov

Drug safety of systemic treatments for psoriasis: results from The German Psoriasis Registry PsoBest. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of dimethylfumarate in elderly psoriasis patients: a multicentric Italian study. [2022]

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

Long-term safety of nine systemic medications for psoriasis: A cohort study using the Spanish Registry of Adverse Events for Biological Therapy in Dermatological Diseases (BIOBADADERM) Registry. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Safety profile of intravenous and subcutaneous siplizumab, an anti-CD2 monoclonal antibody, for the treatment of plaque psoriasis: results of two randomized, double-blind, placebo-controlled studies. [2019]

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

Suspected oncologic adverse reactions associated with interleukin-23 inhibitors in EudraVigilance: Comparative study and gender distribution. [2023]

11. India pubmed.ncbi.nlm.nih.gov

The Impact of Tofacitinib on Quality of Life in Patients with Moderate-to-Severe Psoriasis- An Observational Study. [2023]

12. New Zealand pubmed.ncbi.nlm.nih.gov

Novel Oral Therapies for Psoriasis and Psoriatic Arthritis. [2021]

13. New Zealand pubmed.ncbi.nlm.nih.gov

Tildrakizumab: An Evidence-Based Review of Its Use in the Treatment of Moderate-to-Severe Chronic Plaque Psoriasis. [2020]

14. England pubmed.ncbi.nlm.nih.gov

Cost per responder analysis of guselkumab versus targeted therapies in the treatment of moderate to severe plaque psoriasis in Germany. [2022]

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

Consistent safety profile with up to 5 years of continuous treatment with guselkumab: Pooled analyses from the phase 3 VOYAGE 1 and VOYAGE 2 trials of patients with moderate-to-severe psoriasis. [2022]