A Study in Patients With Moderate to Severe Plaque Psoriasis to Evaluate the Efficacy and Safety of ESK-001 (ONWARD2)

A Multicenter, Randomized, Double-Blind, Placebo and Active Comparator Controlled Phase 3 Study in Patients With Moderate to Severe Plaque Psoriasis to Evaluate the Efficacy and Safety of ESK-001 (ONWARD2)

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.

Study Overview

• Status: Completed
• Conditions: Plaque Psoriasis
• Intervention / Treatment: Drug: Placebo; Drug: Apremilast; Drug: Envudeucitinib

• Study Type: Interventional
• Enrollment (Actual): 862
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Vienna
    • Vienna, Vienna, Austria, 1220
      • Klinik Hietzing
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3E 0B2
      • Beacon Dermatology
    • Edmonton, Alberta, Canada, T6G 1C3
      • Alberta DermaSurgery
    • Edmonton, Alberta, Canada, T6H 4J8
      • VIDA Dermatology/VIDA Clinical Research
    • Red Deer, Alberta, Canada, T4P 1K4
      • CARe Clinic Red Deer
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1E 1V4
      • Skincare Studio
  • Ontario
    • Ajax, Ontario, Canada, L1S 7K8
      • CCA Medical Research Corp
    • Barrie, Ontario, Canada, L4M 7G1
      • SimcoDerm Medical and Surgical Dermatology Center
    • Cobourg, Ontario, Canada, K9A 0Z4
      • Skin Health
    • Guelph, Ontario, Canada, N1L 0B3
      • Guelph Dermatology Research
    • London, Ontario, Canada, N5X 2P1
      • Mediprobe Research
    • Newmarket, Ontario, Canada, L3Y 5G8
      • Clear Skin Dermatology
    • North Bay, Ontario, Canada, P1B 3Z7
      • North Bay Dermatology Centre
    • Oakville, Ontario, Canada, L6H 6P8
      • Rejuvination Dermatology Oakville
    • Toronto, Ontario, Canada, M3H 5Y8
      • Toronto Research Centre
    • Windsor, Ontario, Canada, N8T 1E6
      • XLR8 Medical Research
  • Quebec
    • Montreal, Quebec, Canada, H2X 2V1
      • Innovaderm
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7K 2C1
      • Skinsense Medical Research
• Estonia
  • Tallinn, Estonia, 10128
    • Center for Clinical and Basic Research AS
  • Tartu, Estonia, 50106
    • Kliiniliste Uuringute Keskus OU
  • Harju
    • Tallinn, Harju, Estonia, 10117
      • Innomedica
  • Tartu
    • Tartu, Tartu, Estonia, 50411
      • Tartu University Hospital
• France
  • Nice, France, 06000
    • Centre Azur Nice
  • Reims, France, 51100
    • Polyclinique de Courlancy
  • Normandy
    • Rouen, Normandy, France, 76031
      • CHU de Rouen
• Germany
  • Kiel, Germany, D-24148
    • MVZ DermaKiel GmbH
  • Magdeburg, Germany, 39104
    • Haut Ambulatorium Magdeburg
  • Osnabrück, Germany, 49074
    • KliFOs Klinische Forschung Osnabruck
  • Bavaria
    • Erlangen, Bavaria, Germany, 91054
      • Universitätsklinikum Erlangen
  • Hesse
    • Darmstadt, Hesse, Germany, 64283
      • Rosenpark Research
  • Lower Saxony
    • Oldenburg, Lower Saxony, Germany, 26133
      • Klinikum Oldenburg
  • Mecklenburg-Vorpommern
    • Schwerin, Mecklenburg-Vorpommern, Germany, 19055
      • Klinische Forschung Schwerin GmbH
  • North Rhine-Westphalia
    • Bochum, North Rhine-Westphalia, Germany, 44793
      • Hautarztpraxis Dr Niesmann and Dr Othlinghaus
    • Münster, North Rhine-Westphalia, Germany, 48149
      • Universitaetsklinikum Muenster
  • Rhinelkand-Palatinate
    • Mainz, Rhinelkand-Palatinate, Germany, 55128
      • Dermatologische Praxis Dres Quist
  • Saxony
    • Dresden, Saxony, Germany, 01097
      • Praxis fur Dermatologie und Venerologie
    • Dresden, Saxony, Germany, 1069
      • Klinische Forschung Dresden GmbH
  • State of Berlin
    • Berlin, State of Berlin, Germany, 10789
      • ISA - Interdisciplinary Study Association GmbH
• Hungary
  • Budapest, Hungary, 1152
    • Uno Medical Trials Kft
  • Debrecen, Hungary, 4027
    • Orvostudomanyi Kutato es Fejleszto Kft
  • Szolnok, Hungary, 5000
    • Allergo Derm Bakos Kft
  • Veszprém, Hungary, 8200
    • Medmare Bt
  • Bács-Kiskun county
    • Kecskemét, Bács-Kiskun county, Hungary, 6000
      • Bacs Kiskun County Teaching Hospital
  • Hajdú-Bihar
    • Debrecen, Hajdú-Bihar, Hungary, 4032
      • Borgyogyaszati Klinika Debreceni Egyetem Orvos es Egeszsegtudomenyi Centrum
  • Hajdú-Bihar Megye
    • Debrecen, Hajdú-Bihar Megye, Hungary, 4031
      • DERMA B Kft
  • Oroshaza
    • Békés, Oroshaza, Hungary, 5900
      • DermaMed Research Kf
• Israel
  • Ramat Gan, Israel, 526200
    • Sheba Tel HaShomer Medical Centre
• Latvia
  • Riga, Latvia, LV1001
    • Riga 1st Hospital
  • Riga, Latvia, LV1003
    • Med Art Clinic
  • Riga, Latvia, LV1003
    • Veselibas Centrs 4
  • Riga, Latvia, LV1009
    • SIA Veseliba un estetika
  • Riga, Latvia, LV1013
    • Veselibas Centrs 4 Filiale Dermatologijas Klinika
  • Kuldigas
    • Kuldīga, Kuldigas, Latvia, LV3301
      • Semigallia Ltd
  • Talsi
    • Talsi, Talsi, Latvia, LV3201
      • Smite Aija Medical Practice in Dermatology Venereology
• Poland
  • Katowice, Poland, 40-568
    • Care Clinic Katowice
  • Lublin, Poland, 20-601
    • Zanamed Medical Clinic sp z o o
  • Warsaw, Poland, 02-172
    • MTZ Clinical Research Sp z o o
  • Warsaw, Poland, 02-953
    • Klinika Ambroziak Dermatologia Kliniczna
  • Wroclaw, Poland, 51-503
    • dermMedica
  • Lesser Poland Voivodeship
    • Krakow, Lesser Poland Voivodeship, Poland, 31-501
      • FutureMeds Krakow
  • Lublin Voivodeship
    • Lublin, Lublin Voivodeship, Poland, 20-573
      • Luxderm
  • Malopolska
    • Krakow, Malopolska, Poland, 30-438
      • Centrum Medyczne dr Rajzer Spolka Zoo
  • Masovian Voivodeship
    • Sochaczew, Masovian Voivodeship, Poland, 96-500
      • RCMed Oddział Sochaczew
    • Warsaw, Masovian Voivodeship, Poland, 00-710
      • Clinical Best Solutions
    • Warsaw, Masovian Voivodeship, Poland, 02-625
      • Centrum Medyczne Evimed
  • Podkarpackie Voivodeship
    • Rzeszów, Podkarpackie Voivodeship, Poland, 50-368
      • Klinika Dermatologii Uniwersytecki Szpital Kliniczny im F Chopina
  • Podlaskie Voivodeship
    • Bialystok, Podlaskie Voivodeship, Poland, 15-375
      • Specderm
  • Pomeranian Voivodeship
    • Gdynia, Pomeranian Voivodeship, Poland, 81-338
      • Pratia Gdynia
  • Silesian Voivodeship
    • Katowice, Silesian Voivodeship, Poland, 40-018
      • Pratia Katowice
    • Katowice, Silesian Voivodeship, Poland, 40-748
      • Research Solutions
  • Łódź Voivodeship
    • Lodz, Łódź Voivodeship, Poland, 90-436
      • Dermoklinika
    • Lodz, Łódź Voivodeship, Poland, 91-363
      • FutureMeds Lodz
• Puerto Rico
  • PR
    • San Juan, PR, Puerto Rico, 00917
      • GCM Medical Group PSC Hato Rey Site
  • Puerto Rico
    • Caguas, Puerto Rico, Puerto Rico, 00725
      • Centro Reumatologico de Caguas
    • Ponce, Puerto Rico, Puerto Rico, 00716
      • Ponce Medical School Foundation Inc
    • Ponce, Puerto Rico, Puerto Rico, 00909
      • Clinical Research Puerto Rico
• Spain
  • Manises, Spain, 46940
    • Hospital de Manises
  • A Coruña
    • Santiago de Compostela, A Coruña, Spain, 15706
      • Hospital Clinico Universitario de Santiago de Compostela
  • Alicante
    • Alicante, Alicante, Spain, 3010
      • University General Hospital Dr Balmis
  • Barcelona
    • Barcelona, Barcelona, Spain, 8041
      • Hospital de la Santa Creu i Sant Pau
  • Madrid
    • Madrid, Madrid, Spain, 28041
      • Hospital Universitario 12 de Octubre
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35203
      • Total Skin and Beauty Dermatology Center, PC
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Chandler Clinical Trials
    • Tucson, Arizona, United States, 85704
      • Noble Clinical Research
  • California
    • Beverly Hills, California, United States, 90211-1705
      • Zenith Research Inc.
    • Encino, California, United States, 91436
      • Raoof MD
    • Long Beach, California, United States, 90805
      • Long Beach Research Institute
    • Los Angeles, California, United States, 90045
      • Dermatology Research Associates
    • Pomona, California, United States, 91767
      • Empire Clinical Research - Pomona
    • Sacramento, California, United States, 95815
      • Integrative Skin Science and Research
    • San Diego, California, United States, 92122
      • UC San Diego
    • Santa Ana, California, United States, 92701
      • Southern California Clinical Research
    • Santa Monica, California, United States, 90404
      • Clinical Science Institute Dermatology Institute
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • FXM Clinical Research Ft. Lauderdale LLC
    • Hialeah, Florida, United States, 33012
      • Direct Helpers Research Center (DHRC)
    • Miami, Florida, United States, 33196
      • Las Mercedes Medical Research
    • Miami, Florida, United States, 33126
      • AppleMed Research Group under WCG
    • Miami, Florida, United States, 33146
      • FAX Pharma Clinical Research Inc
    • Miami, Florida, United States, 33175
      • FXM Clinical Research - Miami LLC
    • Miramar, Florida, United States, 33027
      • FXM Clinical Research Miramar LLC
    • Ocala, Florida, United States, 34470
      • Renstar Medical Research
  • Indiana
    • Clarksville, Indiana, United States, 47129
      • DS Research of Southern Indiana
    • Plainfield, Indiana, United States, 46168
      • The Indiana Clinical Trials Center
  • Kentucky
    • Louisville, Kentucky, United States, 40241
      • DS Research of Kentucky
  • Michigan
    • Clarkston, Michigan, United States, 48346
      • Michigan Center for Research Company
    • Detroit, Michigan, United States, 48202
      • Henry Ford Medical Center - Farmington Road
    • Troy, Michigan, United States, 48084
      • Revival Research Institute
    • Warren, Michigan, United States, 48088
      • Grekin Skin Institute
  • Minnesota
    • New Brighton, Minnesota, United States, 55112
      • Associated Skin Care Specialists - Minnesota Clinical Study Center
  • Nebraska
    • Omaha, Nebraska, United States, 68144
      • Schlessinger MD
  • Nevada
    • Las Vegas, Nevada, United States, 89030
      • Las Vegas Clinical Trials
  • New York
    • Elmhurst, New York, United States, 11373
      • NYC Health and Hospitals Elmhurst
    • New York, New York, United States, 10016
      • Pioneer Clinical Research NY
    • New York, New York, United States, 10023
      • Cameron Dermatology
    • Stony Brook, New York, United States, 11790
      • DermResearchCenter of New York
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Asheville Clinical Trials
    • Wilmington, North Carolina, United States, 28405
      • WDC Cosmetic and Research
  • Ohio
    • Boardman, Ohio, United States, 44512
      • Optima Research Boardman
  • Rhode Island
    • Johnston, Rhode Island, United States, 02919
      • Clinical Partners LLC
  • Texas
    • Dallas, Texas, United States, 75231
      • Modern Research Associates PLLC
    • Mesquite, Texas, United States, 75149
      • SMS Clinical Research
    • San Antonio, Texas, United States, 78213
      • Progressive Clinical Research - San Antonio
    • Webster, Texas, United States, 77598
      • Center for Clinical Studies (CCS) - Webster/Clear Lake Location
  • Utah
    • South Jordan, Utah, United States, 84095
      • Jordan Valley Dermatology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Males or females, age ≥18 years
2. Diagnosis of plaque psoriasis for ≥6 months
3. Plaques covering ≥10% of BSA
4. PASI ≥12
5. sPGA ≥3
6. Women of childbearing potential (WOCBP) and males who are sexually active with WOCBP must agree to adhere to highly effective methods of contraception

Exclusion Criteria:

1. Nonplaque psoriasis or other inflammatory skin conditions
2. Immune-mediated conditions commonly associated with psoriasis (eg inflammatory bowel disease). Patients with psoriatic arthritis may participate
3. Pregnant, lactating, or planning to get pregnant during the study

4. Use of drugs prior to Study Day 1 that treat or may affect psoriasis:

   • Topical within 2 weeks
   • Phototherapy or any systemic treatments within 4 weeks
   • Any biologic agent targeted to IL-12 or IL-23 within 6 months, oral IL-12 or IL-23 or TNFα inhibitor within 2 months, or IL-17 within 4 months
   • Systemic immunosuppressants or immunomodulatory drugs within 4 weeks
   • Modulators of B cells within 6 months, or T cells within 3 months
   • JAK inhibitors or TYK2 inhibitors within 4 weeks
   • PDE4 inhibitor within 2 months
   • Any investigational agent, within 30 days or 5 half-lives or is currently enrolled in an investigational study
5. Lack of clinical response to a TYK2, IL-12, or IL-23 targeted psoriasis treatment
6. Patients with QTcF >450 msec (males) or >470 msec (females) at Screening
7. Unstable cardiovascular disease, defined as a recent clinical deterioration or a cardiac hospitalization within the last 3 months
8. Evidence of recent or recurrent herpes zoster or herpes simplex viral infection
9. Evidence of active infection or positive test result for hepatitis B, hepatitis C, HIV or TB
10. History of serious bacterial, fungal, or viral infections that led to hospitalization, or any recent serious infection requiring antibiotic treatment
11. Any history of known or suspected congenital or acquired immunodeficiency state or condition that would compromise the patient's immune status
12. Lab abnormalities indicating significant renal, hepatic or bone marrow dysfunction
13. History of any immune-mediated or inflammatory medical condition for which patient requires current systemic corticosteroids

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Matching oral placebo	Drug: Placebo; Placebo
Experimental: ESK-001; ESK-001 administered as an oral tablet	Drug: Envudeucitinib; ESK-001
Active Comparator: Apremilast; Apremilast administered as an oral capsule	Drug: Apremilast; Apremilast

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine whether ESK-001 reduces the severity of psoriasis by 75% (using the PASI) or by at least 2 points (using sPGA score) compared to placebo	Proportion of patients achieving ≥75% reduction in PASI score. Proportion of patients achieving a score of 0 or 1 on sPGA.	16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To compare the Psoriasis Area and Severity Index (PASI-90 and PASI-100) between ESK-001 and placebo or apremilast	Proportion of patients achieving of ≥90% or 100% reduction in PASI	24 weeks
To compare the Psoriasis Area and Severity Index (PASI-75) between ESK-001 and apremilast	Proportion of patients achieving of ≥75% reduction in PASI	24 weeks
To compare the Static Physician's Global Assessment (sPGA-0/1) between ESK-001 and apremilast	Proportion of patients achieving a score of 0 or 1 on sPGA	24 weeks
To compare the affected body surface area (%BSA) between ESK-001 and placebo or apremilast	Change from baseline in %BSA	24 weeks
To compare the scalp specific Physician's Global Assessment (ssPGA) between ESK-001 and placebo or apremilast	Proportion of patients achieving a score of 0 or 1 on ssPGA	24 weeks
To compare the Psoriasis Symptoms and Signs Diary (PSSD) between ESK-001 and placebo or apremilast	Proportion of patients achieving a score of 0	24 weeks
To compare the Dermatology Life Quality Index (DLQI) between ESK-001 and placebo or apremilast	Proportion of patients achieving a score of 0 or 1	24 weeks
To compare the Pruritus numeric rating scale (NRS) between ESK-001 and placebo	Change from baseline in Pruritus NRS (scale is from 0 (no pain) to 10 (severe pain)).	24 weeks
Proportion of patients with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)	Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)	24 weeks
To characterize the pharmacokinetics of ESK-001	Maximum [Cmax] and minimum [Cmin] plasma concentration	24 weeks

Collaborators and Investigators

• Sponsor: Alumis Inc

Study record dates

Study Major Dates

• Study Start (Actual): August 20, 2024
• Primary Completion (Actual): September 23, 2025
• Study Completion (Actual): December 18, 2025

Study Registration Dates

• First Submitted: September 7, 2024
• First Submitted That Met QC Criteria: September 7, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 9, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases, Papulosquamous; Skin Diseases; Psoriasis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Antirheumatic Agents; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Phosphodiesterase Inhibitors; Phosphodiesterase 4 Inhibitors; apremilast
• Other Study ID Numbers: ESK-001-017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The Sponsor Alumis Inc. is a clinical-stage biopharmaceutical company that has not yet adopted an Individual Participant Data (IPD) sharing plan.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No