Phase 2 Placebo-controlled Study to Assess the Safety, Efficacy, and PK of ESK-001 in SLE

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] - Immune System Diseases [C20]

Trial duration

20 Oct 2023 → ongoing

Decision date (initial)

2023-08-29

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Alumis Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Efficacy, Others, Safety, Pharmacokinetic, Pharmacogenetic, Therapy

• Part A: To compare the effect on disease activity measured by the proportion of patients achieving
British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA)
response at week 48 between doses of ESK-001 and placebo
• Part B: To assess the safety and tolerability of ESK-001 at a single dose.

Secondary objectives 1

1. To assess the safety and tolerability of multiple dose levels of ESK-001 and various other assessments and comparisons as described in Protocol Section 2 “Study Objectives and Endpoints”.

Conditions and MedDRA coding

Systemic lupus erythematosus

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Able and willing to provide written informed consent (signed and dated) to participate in this study and comply with all requirements in the study protocol
2. Males or females, age 18 to 70 years, inclusive, at the time of informed consent
3. Body mass index 18 to 40 kg/m2 and total body weight >40 kg (88 lbs)
4. Adequate peripheral venous access
5. Diagnosed with SLE ≥6 months prior to screening, fulfills the 2019 European League Against Rheumatism (EULAR)/ACR criteria at the time of screening
6. Clinical SLEDAI-2K score ≥4 points with skin involvement prior to first administration of study drug
7. Currently receives at least 1 of the following: • A stable dose of oral corticosteroid as defined in the protocol • And/or antimalarial treatment (e.g., hydroxychloroquine, chloroquine, quinacrine), • And/or no more than 1 of the conventional DMARDS as detailed in the protocol
8. Negative serum ß-human chorionic gonadotropin (ß-hCG) test at screening (women of childbearing potential [WOCBP] only) Please see the protocol for the full list of inclusion criteria.

Exclusion criteria 13

1. Pregnant, lactating, or planning to get pregnant during the study period and for 1 month after study completion or discontinuation
2. Patients with QTcF >450 msec on ECG at screening
3. Drug-induced SLE or other autoimmune diseases that, in the opinion of the Investigator, are likely to confound efficacy assessments
4. Active, proliferative lupus nephritis that in the Investigator’s opinion may require treatment not allowed by the protocol
5. Current disease other than SLE that, in the opinion of the Investigator, is likely to interfere with SLE disease activity assessments.
6. Active severe or unstable neuropsychiatric SLE as defined in the protocol
7. History of or current diagnosis of catastrophic antiphospholipid syndrome within 12 months prior to signing the ICF
8. History of any recurrent non-SLE disease that required treatment with oral or parenteral Corticosteroids as defined in the protocol
9. Receipt of any commercially available biologic agent within 5 half-lives prior to signing of the ICF
10. Receipt of B cell-depleting therapy <6 months prior to signing the ICF or, if therapy was administered >6 months prior to signing the ICF, absolute B cell within the limits as defined in the protocol
11. Has received any therapeutic agent targeted to IL-12, IL-17, or IL-23 within 6 months or any tumor necrosis factor alpha inhibitor(s) within 12 weeks of prior to signing the ICF
12. Has received JAK inhibitors (eg, baricitinib, tofacitinib) or TYK2 inhibitors within 12 weeks of prior to signing the ICF
13. Any of the following: • Currently active, clinically significant infection of any kind • Clinically significant chronic infection (eg, osteomyelitis, bronchiectasis) within 8 weeks prior to signing the ICF • Any infection requiring hospitalization or treatment with IV anti-infectives not completed at least 4 weeks prior to signing the ICF Please see the protocol for the full list of exclusion criteria.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The composite endpoint defined by meeting all of the criteria as described in Protocol Section 2 “Study Objectives and Endpoints”.

Secondary endpoints 1

1. Incidence of treatment-emergent AEs (TEAEs) and SAEs, vital signs, physical examination, 12-lead ECG, and clinical laboratory tests (hematology, clinical chemistry, urinalysis); other measurements and composite endpoints as described in Protocol Section 2 “Study Objectives and Endpoints”.

Investigational products

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

Test 1

Placebo 1

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 13

Locations

8 EU/EEA countries · 31 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 265 files

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

Application history

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