Clinical Trials/NCT05966480

NCT05966480

Active, not recruiting

Phase 2

A Phase 2, Multicenter, Multinational, Randomized, Double-blind, Placebo-Controlled Study to Assess the Safety, Efficacy, and Pharmacokinetics of Multiple Dose Levels of ESK-001 in Adult Patients With Systemic Lupus Erythematosus

Alumis Inc169 sites in 2 countries408 target enrollmentJune 26, 2023

ConditionsSLE

InterventionsESK-001 Placebo

Overview

Phase: Phase 2
Intervention: ESK-001
Conditions: SLE
Sponsor: Alumis Inc
Enrollment: 408
Locations: 169
Primary Endpoint: 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
Status: Active, not recruiting
Last Updated: 9 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this study is to assess the clinical efficacy, safety, PK, and PD of multiple dose levels of ESK-001 compared with placebo in adult patients with SLE.

Detailed Description

This study will consist of a 5 week screening period, 48 week treatment period, and a 4 week follow up period for a total of 57 weeks. Each participant will be randomized to receive ESK-001 or placebo for 48 weeks. An open label extension study will be available for those patients who complete the study.

Registry

clinicaltrials.gov

Start Date

June 26, 2023

End Date

September 1, 2027

Last Updated

9 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Alumis Inc

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Patients with 6 or more months of SLE according to the 2019 EULAR/ACR criteria, have positive autoantibodies or low complement at screening, and have active SLE as measured by SLEDAI-2K of 6 or more, or 4 or more if joint involvement is present.
•Patients need to be on treatment which can be:
•A stable dose of oral corticosteroid (≤40 mg/day prednisone or equivalent) for a minimum of 2 weeks prior to signing of the informed consent form (ICF) at the Screening Visit. The dose of oral corticosteroid the patient is taking should not increase between screening and Week 0 (Day 1).
•And/or antimalarial treatment (e.g., hydroxychloroquine, chloroquine, quinacrine),
•And/or no more than 1 of the following conventional DMARDS:
•Azathioprine ≤200 mg/day
•Mycophenolate mofetil ≤2 g/day or mycophenolic acid ≤1.44 g/day
•Oral, subcutaneous, or intramuscular (IM) methotrexate ≤20 mg/week.

Exclusion Criteria

•Drug-induced SLE or other autoimmune diseases that, in the opinion of the Investigator, are likely to confound efficacy assessments
•Active, proliferative lupus nephritis that in the Investigator's opinion may require treatment not allowed by the protocol
•Current disease other than SLE that, in the opinion of the Investigator, is likely to interfere with SLE disease activity assessments. Examples include severe fibromyalgia, severe osteoarthritis and severe cardiorespiratory diseases.
•Active severe or unstable neuropsychiatric SLE including, but not limited to the following: aseptic meningitis; cerebral vasculitis; myelopathy; demyelination syndromes (ascending or transverse myelitis, acute inflammatory demyelinating polyradiculopathy); acute confusional state; impaired level of consciousness; psychosis; acute stroke or stroke syndrome; cranial neuropathy; new seizures; cerebellar ataxia; and mononeuritis multiplex.
•That would make the patient unable to fully understand the ICF, or
•Where, in the opinion of the Principal Investigator, protocol-specified SOC is insufficient and utilization of a more aggressive therapeutic approach not permitted in the protocol, is indicated
•Known history of a primary immunodeficiency or an underlying condition such as HIV infection or splenectomy that predisposes the patient to infection
•Currently active, clinically significant infection of any kind
•Clinically significant chronic infection (eg, osteomyelitis, bronchiectasis) within 8 weeks prior to signing the ICF (chronic fungal nail infections are allowed)
•Any infection requiring hospitalization or treatment with IV anti-infectives not completed at least 4 weeks prior to signing the ICF

Arms & Interventions

ESK-001 Dose Level 2

ESK-001 administered as an oral tablet

Intervention: ESK-001

ESK-001 Dose Level 1

ESK-001 administered as an oral tablet

Intervention: ESK-001

ESK-001 Dose Level 3

ESK-001 administered as an oral tablet

Intervention: ESK-001

Placebo

Placebo administered as an oral tablet

Intervention: Placebo

Outcomes

Primary Outcomes

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

Time Frame: Week 48

Secondary Outcomes

To compare the effect on disease activity measured by the proportion of patients achieving BICLA responses at Week 48 between doses of ESK-001 and placebo by stratification groups(Week 48)
To use the SF-36 (Short Form-36 item QoL measure) to compare the effect on health-related quality of life (HRQOL) between doses of ESK-001 and placebo(Week 48)
To compare disease-specific QoL between doses of ESK-001 and placebo(Week 48)
To compare corticosteroid use in patients at Week 48(Week 48)
To compare the Lupus Low Disease Activity State (LLDAS) response between doses of ESK-001 and placebo at Week 48(Week 48)
To use the SLE-specific Lupus Quality of Life (LQoL) questionnaire to compare the effect on health-related quality of life (HRQOL) between doses of ESK-001 and placebo(Week 48)
To assess the safety and tolerability of multiple dose levels of ESK-001(Week 48)
To compare the effect on disease activity measured by the proportion of patients achieving an SLE Responder Index of ≥4 (SRI[4]) response at Week 48(Week 48)
To compare the effect on cutaneous disease activity measured by the proportion of patients with a CLASI activity score of ≥8 at baseline achieving ≥ 50% reduction in the CLASI activity score at Week 48 between doses of ESK-001 and placebo(Week 48)
To compare the annualized flare rate through Week 48(Week 48)
To compare Fatigue measured by FACIT-F between doses of ESK-001 and placebo(Week 48)
To compare patient global assessment of disease activity (PtGA) between doses of ESK-001 and placebo(Week 48)