Randomized, Double-Blind, Placebo and Active Comparator Controlled Phase 3 Study for Moderate to Severe Plaque Psoriasis to Evaluate Efficacy and Safety of ESK-001 (ONWARD2)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Alumis Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

20 Feb 2025 → 13 Feb 2026

Decision date (initial)

2025-01-27

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Alumis Inc.

External identifiers

EU CT number

2023-508959-39-00

ClinicalTrials.gov

NCT06588738

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy, Pharmacodynamic, Pharmacokinetic

To determine whether efficacy of ESK-001 is superior to placebo at Week 16

Secondary objectives 3

1. To determine whether efficacy of ESK-001 is superior to apremilast at Weeks 16 and 24
2. To assess the safety and tolerability of ESK-001 over 24 weeks of treatment
3. To characterize the pharmacokinetics of ESK-001

Conditions and MedDRA coding

Moderate to Severe Plaque Psoriasis

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

IPD plan description

SM-03: Primary and secondary end points updated to align with Protocol Amendment v3.0 dated 10-Mar-2025 included in SM-03 application, translations also updated accordingly. Detailed description of the revised text is provided in SM-03 Substantial Modification Description document.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

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

Exclusion criteria 19

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 (eg, deucravacitinib), IL-12, or IL-23 (eg, ustekinumab, risankizumab) 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 * Patients requiring medications to treat underlying stable chronic cardiovascular disease should be on a stable dose for at least 4 weeks before Study Day 1
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 * Stable doses of inhaled corticosteroids for treatment of asthma are allowed
14. Known current malignancy or current evaluation for a potential malignancy or history of malignancy within the past 5 years prior to screening, except for adequately treated basal cell or squamous cell skin carcinoma or carcinoma in situ of the cervix
15. Live vaccines within 4 weeks prior to Study Day 1
16. Patient has planned surgery during the study period * Minor surgical procedures may be allowed
17. Any acute or chronic illness/condition or evidence of an unstable clinical condition that, in the opinion of the Investigator, will substantially increase the risk to the patient if he or she participates in the study
18. History of mental illness within the last 5 years, unless receiving a fixed regimen of psychiatric medications for at least 6 months before screening or has not required or been prescribed any psychiatric medication within 12 months before screening
19. Evidence of severe depressive symptoms or active suicidal ideation or behavior based on screening questionaires

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The proportion of patients who achieve co-primary endpoint (PASI-75 & sPGA-0/1) at Week 16 compared with Placebo

Secondary endpoints 2

1. Week 16 Endpoints: *The proportion of patients who achieve PASI-90, PASI-100, sPGA-0 PASI-75 and sPGA-0/1 compared to apremilast ss-PGA-0/1 PROs: PSSD-0 and DLQI-0/1 *Change from baseline in %BSA Pruritis NRS score
2. Week 24 Endpoints compared to apremilast: *The proportion of patients who achieve PASI-75, PASI-90, PASI-100 sPGA-0/1, sPGA-0 ss-PGA-0/1 PROs: PSSD-0 and DLQI-0/1 *Change from baseline %BSA Pruritis NRS score

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 3

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Alumis Inc.

Sponsor organisation

Alumis Inc.

Address

280 East Grand Avenue

City

South San Francisco

Postcode

94080-4808

Country

United States

Scientific contact point

Organisation

Alumis Inc.

Contact name

Clinical Trial Information Desk

Public contact point

Organisation

Alumis Inc.

Contact name

Clinical Trial Information Desk

Third parties 11

Locations

9 EU/EEA countries · 83 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 171 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications