ESK-001 for Plaque Psoriasis

(ONWARD3 Trial)

Recruiting at 233 trial locations

Overseen By Alumis Information

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Alumis Inc

Must be taking: ESK-001

Disqualifiers: Pregnant, Unstable condition, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

1680 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and effectiveness of the drug ESK-001 when taken long-term by individuals with moderate to severe plaque psoriasis. The researchers aim to determine if ESK-001 can reduce the severity of symptoms associated with this skin condition. Participants will initially take ESK-001 openly for 24 weeks, after which some will randomly switch to a placebo while others continue with the drug. The trial seeks participants who have already completed a previous study with ESK-001 for moderate to severe plaque psoriasis. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the potential availability of a new treatment.

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 study team or your doctor.

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

Research has shown that ESK-001 is generally safe and well-tolerated in people with moderate-to-severe psoriasis. After 12 weeks of treatment, patients experienced no major safety issues. Earlier studies on healthy individuals also found ESK-001 to be safe and well-tolerated.

Patients using ESK-001 for extended periods continued to experience positive results without new safety concerns. This suggests that ESK-001 might be safe for long-term use, though further studies are needed to confirm this. Prospective trial participants may find this information reassuring regarding the safety of ESK-001. ^{1 2 3 4 5}

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

Most treatments for plaque psoriasis, like biologics and topical steroids, aim to reduce inflammation by targeting proteins in the immune system. But ESK-001 works differently, acting as an oral tablet that specifically targets a new pathway involved in skin cell growth and immune response. This distinct mechanism offers potential benefits in terms of efficacy and safety. Researchers are excited about ESK-001 because it could provide a more convenient oral treatment option with a novel approach to managing plaque psoriasis, potentially offering relief to those who have not responded well to existing therapies.

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

Research has shown that ESK-001 holds promise for treating moderate to severe plaque psoriasis. In earlier studies, ESK-001 improved patient outcomes based on the dose, with higher doses leading to better results. In this trial, participants may receive either a blinded or open-label administration of ESK-001. Specifically, patients taking 40 mg twice a day experienced significant and lasting improvements, with many achieving a 75% or 90% reduction in psoriasis severity. These findings suggest that ESK-001 could effectively reduce the severity of plaque psoriasis over the long term. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

This trial is for adults over 18 who have moderate to severe plaque psoriasis and completed a prior ESK-001 study. Participants must commit to daily medication, regular clinic visits, and providing blood and urine samples.

Inclusion Criteria

Completed either of the two previous (parent) studies of ESK-001 (ESK-001-016 or ESK-001-017)

I tolerated the ESK-001 treatment well in a previous study.

I agree to use effective birth control during the study.

Exclusion Criteria

Pregnant, lactating, or planning to get pregnant during the study period

Deemed by the Investigator to be inappropriate for the study or unable to comply with the protocol

I don't have any health conditions that make it unsafe for me to receive ESK-001 treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Open-label Treatment

Participants receive open-label ESK-001 twice daily for 24 weeks

24 weeks

Regular clinic visits for checkups and assessments

Randomized Withdrawal

First 200 patients meeting PASI-75 response are randomized to ESK-001 or placebo; others continue open-label treatment

24 weeks

Regular clinic visits for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label Extension

Participants return to open-label ESK-001 treatment until the end of the study or discontinuation

Until study completion

What Are the Treatments Tested in This Trial?

Interventions

• ESK-001

Trial Overview The trial tests the long-term safety and effectiveness of ESK-001 in reducing plaque psoriasis severity. Initially, all participants receive open-label ESK-001; after 24 weeks, some may switch to placebo or continue with the drug based on their response.

How Is the Trial Designed?

Group I: Open-Label ESK-001 Experimental Treatment 1 Intervention

Open-Label ESK-001 administered as an oral tablet

Group II: Blinded ESK-001 Experimental Treatment 1 Intervention

Blinded ESK-001 administered as an oral tablet

Group III: Placebo Placebo Group 1 Intervention

Matching placebo administered as an oral tablet

Who Is Running the Clinical Trial?

Alumis Inc

Lead Sponsor

Trials

9

Recruited

4,200+

Citations

1. jaad.org jaad.org/article/S0190-9622(25)02466-1/fulltext

Highly selective, allosteric inhibition of TYK2 with oral ESK- ... ESK-001 demonstrated a dose-dependent improvement across all end points, with maximal efficacy observed in the highest dose arm (40 mg BID).

2. 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 ...

3. 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 ...

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. 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 ... Improvements were durable with this dose, with 83% and 85% of patients maintaining PASI 75 and PASI 90, respectively, during a 4-week off- ...

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

Safety, tolerability, pharmacokinetics, and pharmacodynamics ... ESK‐001 was generally safe and well‐tolerated in healthy participants, showed linear dose‐dependent PK characteristics, and maximally inhibited TYK2‐dependent ...