ESK-001 for Psoriasis

(ONWARD1 Trial)

Recruiting at 40 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Alumis Inc

Must not be taking: Biologics, Immunosuppressants, JAK inhibitors, others

Disqualifiers: Nonplaque psoriasis, Immune-mediated conditions, Pregnancy, others

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to learn if ESK-001 works to treat moderate to severe plaque psoriasis. The main questions it aims to answer are: * Does ESK-001 reduce the severity of people's psoriasis? * How safe is ESK-001 in people with moderate to severe plaque psoriasis? The study includes 2 comparators: a placebo control (a 'dummy' tablet that does not contain the medicine ESK-001 but looks just like it) and an active control (apremilast, which is a medicine approved to treat psoriasis). People taking part in this study must be men or women aged at least 18 years and have had plaque psoriasis for at least 6 months, currently moderate to severe. Participants will: * take drug every day for 24 weeks. * visit the clinic for checkups and tests. * fill out questionnaires about their psoriasis, itch severity, and change in quality of life. * be assessed for health issues and side effects, physical examinations, vital signs, heart electrical activity measurements, and psychological health. * provide blood and urine samples.

Will I have to stop taking my current medications?

Yes, you may need to stop taking certain medications before joining the trial. Specifically, you must not have used topical treatments for psoriasis within 2 weeks, phototherapy or systemic treatments within 4 weeks, and certain biologic agents or immunosuppressants within specified time frames before the study starts.

What evidence supports the effectiveness of the drug ESK-001 for treating psoriasis?

Research shows that targeting interleukin-23, a protein involved in immune responses, can improve psoriasis symptoms. Drugs like tildrakizumab and guselkumab, which target this protein, have shown significant improvement in patients with moderate-to-severe psoriasis, suggesting that ESK-001 might work similarly if it targets the same pathway. ^{1 2 3 4 5}

How does the drug ESK-001 differ from other psoriasis treatments?

ESK-001 may be unique in targeting the mitogen- and stress-activated protein kinase (MSK) pathway, which is involved in the production of pro-inflammatory cytokines that contribute to psoriasis. This approach could offer a novel way to reduce inflammation compared to existing treatments that focus on other pathways. ^{6 7 8 9 10}

Eligibility Criteria

Adults aged 18+ with moderate to severe plaque psoriasis for at least 6 months can join this study. They'll take a daily drug for half a year, visit the clinic regularly, and report on their skin condition, itchiness, and life quality changes.

Inclusion Criteria

Have you been diagnosed with Plaque Psoriasis?

Exclusion Criteria

Have you been diagnosed with Inflammatory Bowel Disease?

Have you been hospitalized for cardiovascular disease in the last 3 months?

Do you have recurring herpes infection or an active infection for Hepatitis B, Hepatitis C, or HIV?

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ESK-001, placebo, or apremilast daily for 24 weeks. They will visit the clinic for checkups, tests, and assessments.

24 weeks

Regular clinic visits for checkups and tests

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of health issues and side effects.

4 weeks

Treatment Details

Interventions

• ESK-001 (Other)

Trial Overview The trial is testing ESK-001's effectiveness in treating plaque psoriasis compared to a placebo (dummy pill) and Apremilast (an approved treatment). Participants will be monitored through clinic visits, questionnaires, health checks, heart activity tests, and by providing blood/urine samples.

Participant Groups

Group I: ESK-001 Experimental Treatment 1 Intervention

ESK-001 administered as an oral tablet

Group II: Apremilast Active Control 1 Intervention

Apremilast administered as an oral capsule

Group III: Placebo Placebo Group 1 Intervention

Matching oral placebo

Who Is Running the Clinical Trial?

Alumis Inc

Lead Sponsor

Trials

9

Recruited

4,200+

Findings from Research

Biological therapies for psoriasis, including monoclonal antibodies and recombinant proteins, target specific pathways in the disease, making them potentially safer and more effective than traditional treatments.

Four biological agents—alefacept, efalizumab, etanercept, and infliximab—are already in clinical use, with many more under investigation, highlighting a significant advancement in psoriasis treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biologicals dramatic advances in the treatment of psoriasis. Wilsmann-Theis, D., Martin, S., Reber, M., et al.[2019]

Tildrakizumab, a monoclonal antibody targeting the IL-23p19 subunit, showed significant clinical improvement in patients with moderate-to-severe psoriasis, with all subjects achieving a 75% reduction in PASI scores by day 196 in the 3 and 10 mg/kg groups.

In a phase I study involving multiple doses, a majority of subjects (10 out of 15 in the 3 mg/kg group and 13 out of 14 in the 10 mg/kg group) achieved PASI75 by day 112, confirming the efficacy of specific IL-23 inhibition in reducing psoriasis severity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical improvement in psoriasis with specific targeting of interleukin-23. Kopp, T., Riedl, E., Bangert, C., et al.[2019]

In two phase III studies involving 1861 patients with moderate to severe plaque psoriasis, tofacitinib significantly improved health-related quality of life, with a higher percentage of patients achieving a Dermatology Life Quality Index score of 1 or less compared to placebo at week 16, and these improvements were maintained through week 52.

Tofacitinib also led to rapid relief from itch, with improvements noticeable just one day after starting treatment, and a greater proportion of patients reported satisfaction with the treatment compared to those on placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tofacitinib improves pruritus and health-related quality of life up to 52 weeks: Results from 2 randomized phase III trials in patients with moderate to severe plaque psoriasis. Feldman, SR., Thaçi, D., Gooderham, M., et al.[2017]

References

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

Guselkumab is superior to fumaric acid esters in patients with moderate-to-severe plaque psoriasis who are naive to systemic treatment: results from a randomized, active-comparator-controlled phase IIIb trial (POLARIS). [2021]

2. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Biologicals dramatic advances in the treatment of psoriasis. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Clinical improvement in psoriasis with specific targeting of interleukin-23. [2019]

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

Tofacitinib improves pruritus and health-related quality of life up to 52 weeks: Results from 2 randomized phase III trials in patients with moderate to severe plaque psoriasis. [2017]

5. England pubmed.ncbi.nlm.nih.gov

Emerging systemic drugs in the treatment of plaque psoriasis. [2021]

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

Mitogen- and stress-activated protein kinase 1 is activated in lesional psoriatic epidermis and regulates the expression of pro-inflammatory cytokines. [2022]

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

Biological activity of tyrosine kinase inhibitors: novel agents for psoriasis therapy. [2009]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Lck signaling inhibition causes improvement in clinical features of psoriatic inflammation through reduction in inflammatory cytokines in CD4+ T cells in imiquimod mouse model. [2022]

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

Mitogen- and stress-activated protein kinase 2 and cyclic AMP response element binding protein are activated in lesional psoriatic epidermis. [2022]

10. Denmark pubmed.ncbi.nlm.nih.gov

Tyrphostins suppress the growth of psoriatic keratinocytes. [2019]