Phase 2 Placebo-Controlled Study to Assess the Safety and Efficacy of ESK-001 in Active Systemic Lupus Erythematosus

SLE Clinical Trial

— LUMUS  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05966480
• Other study ID #: ESK-001-010
• Status: Recruiting
• Phase: Phase 2
• Start date: June 26, 2023
• Est. completion date: December 1, 2025

Study information

• Verified date: April 2024
• Source: Alumis Inc
• Contact: Central Recruiting
• Phone: (+1) 650-538-2502
• Email: clinicaltrials[@]alumis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 388
• Est. completion date: December 1, 2025
• Est. primary completion date: May 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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
• Any infection requiring oral anti-infectives (including antivirals) within 2 weeks prior to Day 1
• Any severe herpes infection at any time prior to Week 0 (Day 1), including, but not limited to, disseminated herpes (ever), herpes encephalitis (ever), recurrent herpes zoster (defined as 2 episodes within 2 years), or ophthalmic herpes (ever)
• Active herpes zoster infection within 12 weeks of prior to signing the ICF
• Active herpes simplex virus within 4 weeks of Day 1
• Other protocol-defined inclusion/exclusion criteria apply

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• SLE

Intervention

Drug:
• ESK-001
Oral tablet
• Placebo
Oral tablet

Locations

Country	Name	City	State
Argentina	Investigator Site #3023	Buenos Aires
Argentina	Investigator Site #3012	Caba	Buenos Aires
Argentina	Investigator Site #3001	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	Investigator Site #3016	La Plata	Buenos Aires
Argentina	Investigator Site #3008	Mendoza
Argentina	Investigator Site #3009	San Miguel de Tucuman	Tucman
Argentina	Investigator Site #3010	San Miguel De Tucumán	Tucman
Argentina	Investigator Site #3015	San Miguel De Tucumán	Tucumán
Bulgaria	Investigator Site #5521	Plovdiv
Bulgaria	Investigator Site #5525	Plovdiv
Bulgaria	Investigator Site #5529	Ruse
Bulgaria	Investigator Site #5522	Sofia
Bulgaria	Investigator Site #5541	Sofia
Bulgaria	Investigator Site #5547	Sofia
Chile	Investigator Site #3006	Providencia
Chile	Investigator Site #3002	Santiago
Colombia	Investigator Site #3011	Barranquilla
Colombia	Investigator Site #3019	Barranquilla
Colombia	Investigator Site #3021	Bogotá
Colombia	Investigator Site #3022	Bogotá
Colombia	Investigator Site #3020	Cali
Colombia	Investigator Site #3003	Chia
Colombia	Investigator Site #3014	Medellín
Croatia	Investigator Site #5542	Rijeka
Croatia	Investigator Site #5543	Split
Denmark	Investigator Site #4011	Køge
Georgia	Investigator Site #5516	Tbilisi
Georgia	Investigator Site #5523	Tbilisi
Georgia	Investigator Site #5534	Tbilisi
Georgia	Investigator Site #5536	Tbilisi
Georgia	Investigator Site #5538	Tbilisi
Germany	Investigator Site #4001	Kirchheim Unter Teck
Germany	Investigator Site #4004	Koeln
Germany	Investigator Site #4003	Leipzig
Germany	Investigator Site #4005	Mainz
Germany	Investigator Site #4006	Munich
Hungary	Investigator Site #5548	Debrecen
Hungary	Investigator Site #5544	Gyula
India	Investigator Site #6005	Ahmedabad
India	Investigator Site #6006	Ahmedabad
India	Investigator Site #6010	Ahmedabad
India	Investigator Site #6001	Bangalore
India	Investigator Site #6009	Bengaluru
India	Investigator Site #6012	Chandigarh
India	Investigator Site #6004	Haryana
India	Investigator Site #6013	Jaipur
India	Investigator Site #6011	Lucknow
India	Investigator Site #6008	Nagpur
India	Investigator Site # 6015	New Delhi	Delhi
India	Investigator Site #6007	Pune
India	Investigator Site #6014	Pune
India	Investigator Site #6002	Surat
India	Investigator Site #6003	Surat
Korea, Republic of	Investigator Site #8007	Anyang-si
Korea, Republic of	Investigator Site #8004	Busan
Korea, Republic of	Investigator Site #8002	Namdong	Incheon
Korea, Republic of	Investigator Site #8012	Seoul
Korea, Republic of	Investigator Site #8016	Seoul
Korea, Republic of	Investigator Site #8019	Seoul
Mexico	Investigator Site #2501	Chihuahua
Mexico	Investigator Site #2503	Ciudad de Mexico
Mexico	Investigator Site #2506	Ciudad De Mexico
Mexico	Investigator Site #2509	Ciudad de Mexico
Mexico	Investigator Site #2504	Cuauhtémoc
Mexico	Investigator Site #2502	Guadalajara
Mexico	Investigator Site #2507	Guadalajara
Mexico	Investigator Site #2512	Guadalajara
Mexico	Investigator Site #2508	Madero
Mexico	Investigator Site #2516	Merida
Mexico	Investigator Site #2511	Mérida
Mexico	Investigator Site #2514	Mexico City
Mexico	Investigator Site # 2517	Naucalpan De Juárez
Mexico	Investigator Site #2510	Oaxaca
Mexico	Investigator Site #2505	San Luis Potosí
Mexico	Investigator Site #2513	Torreon
Peru	Investigator Site #3004	Lima
Peru	Investigator Site #3013	Lima
Peru	Investigator Site #3018	San Martin De Porres
Peru	Investigator Site #3005	Santiago De Surco
Peru	Investigator Site #3017	Trujillo
Philippines	Investigator Site #8003	Angeles City
Philippines	Investigator Site #8009	Iloilo City
Philippines	Investigator Site #8011	Lipa City
Philippines	Investigator Site #8001	Manila
Philippines	Investigator Site #8010	Manila
Philippines	Investigator Site #8018	Manila
Philippines	Investigator Site #8006	Quezon City
Poland	Investigator Site #5518	Bialystok
Poland	Investigator Site #5519	Bialystok
Poland	Investigator Site #5546	Bialystok
Poland	Investigator Site #5531	Bydgoszcz
Poland	Investigator Site #5520	Bytom
Poland	Investigator Site #5539	Czestochowa
Poland	Investigator Site #5533	Kraków
Poland	Investigator Site #5537	Nadarzyn
Poland	Investigator Site #5545	Poznan
Poland	Investigator Site #5535	Sosnowiec
Poland	Investigator Site #5532	Szczecin
Poland	Investigator Site #5527	Warsaw
Poland	Investigator Site #5540	Warszawa
Poland	Investigator Site #5528	Wroclaw
Romania	Investigator Site #5526	Bucuresti
Romania	Investigator Site #5530	Bucuresti
Romania	Investigator Site #5549	Bucuresti
Spain	Investigator Site #4013	A Coruña
Spain	Investigator Site #4008	Alicante
Spain	Investigator Site #4007	Barcelona
Spain	Investigator Site #4002	Sevilla
Spain	Investigator Site #4009	Valencia
Taiwan	Investigator Site #8013	Chiayi City
Taiwan	Investigator Site #8014	Kaohsiung City
Taiwan	Investigator Site #8008	Taichung
Taiwan	Investigator Site #8015	Taichung
Taiwan	Investigator Site #8017	Taipei
United Kingdom	Investigator Site #4017	Leeds
United Kingdom	Investigator Site #4015	London
United Kingdom	Investigator Site #4016	London
United Kingdom	Investigator Site #4014	Southampton
United States	Investigator Site #1046	Anniston	Alabama
United States	Investigator Site #1048	Aventura	Florida
United States	Investigator Site #1063	Avon Park	Florida
United States	Investigator Site #1058	Brooklyn	New York
United States	Investigator Site #1077	Burlington	Massachusetts
United States	Investigator Site #1056	Charlotte	North Carolina
United States	Investigator Site #1095	Charlotte	North Carolina
United States	Investigator Site #1045	Clearwater	Florida
United States	Investigator Site #1052	College Park	Georgia
United States	Investigator Site #1049	Colleyville	Texas
United States	Investigator Site #1055	Coral Gables	Florida
United States	Investigator Site #1097	Coral Springs	Florida
United States	Investigator Site #1051	DeBary	Florida
United States	Investigator Site #1087	Hollywood	Florida
United States	Investigator Site #1096	Hoover	Alabama
United States	Investigator Site #1094	Houston	Texas
United States	Investigator Site #1092	Lansing	Michigan
United States	Investigator Site #1050	Los Alamitos	California
United States	Investigator Site #1044	Memphis	Tennessee
United States	Investigator Site #1057	Miami	Florida
United States	Investigator Site #1060	Miami	Florida
United States	Investigator Site #1093	Miami	Florida
United States	Investigator Site #1062	Pittsburgh	Pennsylvania
United States	Investigator Site #1090	Plantation	Florida
United States	Investigator Site #1089	Tampa	Florida
United States	Investigator Site #1061	Upland	California

Sponsors (1)

Lead Sponsor	Collaborator
Alumis Inc

Countries where clinical trial is conducted

United States,  Argentina,  Bulgaria,  Chile,  Colombia,  Croatia,  Denmark,  Georgia,  Germany,  Hungary,  India,  Korea, Republic of,  Mexico,  Peru,  Philippines,  Poland,  Romania,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		Week 48
Secondary	To assess the safety and tolerability of multiple dose levels of ESK-001	Safety and Tolerability will be assessed with clinical and laboratory assessments including blood tests for liver and kidney function, ECGs, hematological measures and physical examinations throughout the time of the study and safety follow up. The number and proportion of TEAEs, SAEs, AEs of greater than grade 3 severity and AEs of Clinical Interest will be recorded.	Week 48
Secondary	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
Secondary	To compare corticosteroid use in patients at Week 48	To compare the number and percentage of patients using corticosteroids and continuous summaries of dose used will be assessed as well as the frequency and percentage of patients able to taper corticosteroids and maintain low doses following taper.	Week 48
Secondary	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
Secondary	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
Secondary	To compare the Lupus Low Disease Activity State (LLDAS) response between doses of ESK-001 and placebo at Week 48		Week 48
Secondary	To compare the annualized flare rate through Week 48		Week 48
Secondary	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	Efficacy: Comparing the effects of Esk-001 doses vs Placebo on Patient Reported Outcome (PRO) as it relates to Health-Related Quality of Life (HRQoL) as measured by self-reporting using the SF-36 (Short Form-36 item QoL measure) Questionnaire which uses a scale of 0 to 100. The higher numbers mean better health.	Week 48
Secondary	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	Efficacy: Comparing the effects of Esk-001 doses vs Placebo on Patient Reported Outcome (PRO) as it relates to Health-Related Quality of Life (HRQoL) as measured by self-reporting using the SLE-specific Lupus Quality of Life (LQoL) questionnaire which uses a scale of 0 to 100. The higher numbers mean better health.	Week 48
Secondary	To compare disease-specific QoL between doses of ESK-001 and placebo	Efficacy: To compare disease-specific QoL between doses of ESK-001 and placebo using the SLE Disease Activity Index 2000 (SLEDAI2K) measured on a scale of 0 to 105 where the higher numbers mean more disease activity.	Week 48
Secondary	To compare disease-specific QoL between doses of ESK-001 and placebo	Efficacy: To compare disease-specific QoL between doses of ESK-001 and placebo using the British Isle Lupus Assessment Group 2004 (BILAG-2004) with a scale of A to E (A meaning very active disease and E no current or previous disease).	Week 48
Secondary	To compare disease-specific QoL between doses of ESK-001 and placebo	Efficacy: To compare disease-specific QoL between doses of ESK-001 and placebo using the Physician's Global Assessment (PGA) evaluating disease response using the 4-point VAS (Visual Analog Scale) of 0 to 3 (0 means no flares and 3 means severe flare in disease).	Week 48
Secondary	To compare Fatigue measured by FACIT-F between doses of ESK-001 and placebo	To compare patient-reported fatigue as measured by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire between doses of ESK-001 and placebo, where the score range is 0 to 52 and a lower score indicates greater fatigue/worse outcome.	Week 48
Secondary	To compare patient global assessment of disease activity (PtGA) between doses of ESK-001 and placebo	Efficacy: To compare disease-specific QoL between doses of ESK-001 and placebo using the PtGA (Patient Global Assessment) instrument. Patients record on a visual analog scale (VAS) how well or badly they feel as a result of the disease in their own estimation over the course of the study.	Week 48