ESK-001 for Plaque Psoriasis

Not currently recruiting at 40 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Alumis Inc

Must not be taking: Prohibited medications

Disqualifiers: Pregnancy, 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests ESK-001, an oral tablet, to evaluate its effects on plaque psoriasis, a skin condition causing itchy, scaly patches. The study extends participation for those who completed an earlier ESK-001 trial, aiming to further assess its effectiveness and safety. Participants will try one of two dose levels to help researchers determine the optimal dosage. This trial is ideal for individuals who have completed a previous ESK-001 psoriasis study. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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

The trial does not specify if you need to stop your current medications, but it mentions that certain medications are prohibited. It's best to check with the trial team to see if your current medications are allowed.

Is there any evidence suggesting that ESK-001 is likely to be safe for humans?

Research has shown that ESK-001, a treatment being tested for plaque psoriasis, has promising safety results from earlier studies. In these studies, participants received ESK-001 as a pill in various doses. The results suggest it is generally well-tolerated by individuals with moderate-to-severe plaque psoriasis. Although specific side effects are not detailed, the treatment's progression to further trials indicates its safety thus far. Participants reported significant improvements without major safety issues, supporting its continued testing. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for plaque psoriasis?

Unlike standard treatments for plaque psoriasis, which often include topical corticosteroids or biologics that target specific immune pathways, ESK-001 is unique because it is administered as an oral tablet. This offers a convenient alternative to injections or topical applications. Additionally, ESK-001 might work through a novel mechanism of action, potentially providing relief for patients who haven't responded well to other therapies. Researchers are excited about ESK-001 because it could offer a more convenient, potentially faster-acting option for managing plaque psoriasis.

What evidence suggests that ESK-001 might be an effective treatment for plaque psoriasis?

Research shows that ESK-001 may help treat plaque psoriasis. This trial will test ESK-001 at different dose levels. Studies have found that ESK-001 significantly improves the signs and symptoms of psoriasis, especially at higher doses. People with moderate-to-severe plaque psoriasis reported feeling better. One study showed that ESK-001 was safe and effective over a 12-week treatment period. For those with plaque psoriasis, these findings suggest that ESK-001 could be a helpful option. ^{2 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for men and women with plaque psoriasis who have finished a previous study involving ESK-001. Participants must commit to using effective contraception throughout the study. Pregnant individuals or those on certain other medications cannot join.

Inclusion Criteria

I will use effective birth control during the study.

Must have completed a prior ESK-001 study

Exclusion Criteria

I have not taken any medication that is not allowed in the study.

Pregnancy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Open-label extension

Participants receive ESK-001 at one of two open-label dose levels until the drug is commercially available

Approximately 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ESK-001

Trial Overview The trial is testing the long-term safety and effectiveness of a medication called ESK-001 in treating plaque psoriasis. It's an open-label extension, meaning everyone knows they're getting ESK-001, and it involves multiple centers.

How Is the Trial Designed?

Group I: ESK-001 Dose Level 2 Experimental Treatment 1 Intervention

ESK-001 administered as an oral tablet

Group II: ESK-001 Dose Level 1 Experimental Treatment 1 Intervention

ESK-001 administered as an oral tablet

Who Is Running the Clinical Trial?

Alumis Inc

Lead Sponsor

Trials

9

Recruited

4,200+

Published Research Related to This Trial

This study found increased activation of MSK2 and CREB in lesional psoriatic skin, suggesting that these proteins may contribute to the development of psoriasis, as evidenced by phospho blotting and immunofluorescence staining.

The research indicates that the p38-MAPK/MSK1/MSK2 and CREB signaling pathway is involved in psoriasis, as activation of this pathway in keratinocytes was inhibited by a p38 inhibitor, highlighting a potential target for therapeutic intervention.

NCBI (Pubmed)

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. Funding, AT., Johansen, C., Kragballe, K., et al.[2022]

This study found that MSK1 is significantly activated in lesional psoriatic skin, indicating its potential role in the inflammatory processes associated with psoriasis.

In cultured human keratinocytes, reducing MSK1 expression led to a notable decrease in the production of key pro-inflammatory cytokines (IL-6, IL-8, and TNF-alpha), suggesting that MSK1 could be a target for therapeutic intervention in psoriasis.

NCBI (Pubmed)

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. Funding, AT., Johansen, C., Kragballe, K., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40659116/

Highly selective, allosteric inhibition of TYK2 with oral ESK ... ESK-001 demonstrated significant dose-dependent improvement in signs and symptoms of psoriasis while achieving continuous target inhibition at the highest dose.

2. alumis.com alumis.com/file.cfm/18/docs/aad2025_pstr_pro_final.pdf

Patient-Reported Outcomes in the Phase 2 Studies of ESK- ... In these Phase 2 studies in patients with moderate-to-severe plaque psoriasis, ESK-001 demonstrated significant improvements in clinical ...

3. dermatologyadvisor.com dermatologyadvisor.com/news/esk-001-may-be-safe-effective-moderate-to-severe-plaque-psoriasis/

ESK-001 May Be Safe, Effective for Moderate to Severe ... ESK-001, a novel therapy for moderate to severe plaque psoriasis, had acceptable safety and efficacy outcomes at 12 weeks of treatment.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06846541

Long-term Safety and Efficacy of ESK-001 in Moderate to ... The objective of the ESK-001-018 long term extension is to evaluate the safety and efficacy of ESK-001 over time. The scientific questions it aims to answer ...

5. investors.alumis.com investors.alumis.com/news-releases/news-release-details/late-breaking-esk-001-phase-2-ole-data-presented-2025-aad-annual?mobile=1&mobile=1

Late-Breaking ESK-001 Phase 2 OLE Data Presented at 2025 ... These data demonstrated that patients receiving 40 mg twice daily dosing of ESK-001 achieved long-term sustained or increasing clinical responses through Week ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11602527/

Safety, tolerability, pharmacokinetics, and ... ESK‐001 is a highly selective allosteric inhibitor of tyrosine kinase 2 (TYK2), which plays an essential role in mediating cytokine ...

7. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-effectiveness-and-safety-of-esk-001-and-apremilast-for-patients-with-moderate-to-severe-plaque-psoriasis/

Study on the Effectiveness and Safety of ESK-001 and ... This clinical trial is focused on studying the effectiveness and safety of a new treatment for Moderate to Severe Plaque Psoriasis.