Clinical trial NCT05966480: Phase 2 Placebo-Controlled Study to Assess the Safety and Efficacy of ESK-001 in Active Systemic Lupus Erythematosus
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: SLE
Keywords: Autoimmune Diseases
Immune System Diseases
Connective Tissue Diseases
Immune-mediated Diseases
Active Systemic Lupus Erythematosus
SLE
Lupus
LUMUS
Lupus Erythematosus, Systemic
Lead sponsor: Alumis Inc
Sponsor class: INDUSTRY
First posted: 2023-07-28
Enrollment: 388
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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
* 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

Primary outcomes:
measure: 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
timeFrame: Week 48
Secondary outcomes:
measure: To assess the safety and tolerability of multiple dose levels of ESK-001
timeFrame: Week 48
measure: 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
timeFrame: Week 48
measure: To compare corticosteroid use in patients at Week 48
timeFrame: Week 48
measure: 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
timeFrame: Week 48
measure: 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
timeFrame: Week 48
measure: To compare the Lupus Low Disease Activity State (LLDAS) response between doses of ESK-001 and placebo at Week 48
timeFrame: Week 48
measure: To compare the annualized flare rate through Week 48
timeFrame: Week 48
measure: 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
timeFrame: Week 48
measure: 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
timeFrame: Week 48
measure: To compare disease-specific QoL between doses of ESK-001 and placebo
timeFrame: Week 48
measure: To compare disease-specific QoL between doses of ESK-001 and placebo
timeFrame: Week 48
measure: To compare disease-specific QoL between doses of ESK-001 and placebo
timeFrame: Week 48
measure: To compare Fatigue measured by FACIT-F between doses of ESK-001 and placebo
timeFrame: Week 48
measure: To compare patient global assessment of disease activity (PtGA) between doses of ESK-001 and placebo
timeFrame: Week 48
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Investigator Site #1046
state: Alabama
city: Hoover
country: United States
facility: Investigator Site #1096
state: Alabama
city: La Jolla
country: United States
facility: Investigator Site #1104
state: California
city: Los Alamitos
country: United States
facility: Investigator Site #1050
state: California
city: Mission Hills
country: United States
facility: Investigator Site #1168
state: California
city: Napa
country: United States
facility: Investigator Site #1174
state: California
city: Upland
country: United States
facility: Investigator Site #1061
state: California
city: Aventura
country: United States
facility: Investigator Site #1048
state: Florida
city: Avon Park
country: United States
facility: Investigator Site #1063
state: Florida
city: Bradenton
country: United States
facility: Investigator Site #1176
state: Florida
city: Clearwater
country: United States
facility: Investigator Site #1045
state: Florida
city: Coral Gables
country: United States
facility: Investigator Site #1055
state: Florida
city: Coral Springs
country: United States
facility: Investigator Site #1097
state: Florida
city: Daytona Beach
country: United States
facility: Investigator Site #1091
state: Florida
city: DeBary
country: United States
facility: Investigator Site #1051
state: Florida
city: Hollywood
country: United States
facility: Investigator Site #1087
state: Florida
city: Kissimmee
country: United States
facility: Investigator Site #1135
state: Florida
city: Miami Lakes
country: United States
facility: Investigator Site #1067
state: Florida
city: Miami
country: United States
facility: Investigator Site #1060
state: Florida
city: Miami
country: United States
facility: Investigator Site #1093
state: Florida
city: Miami
country: United States
facility: Investigator Site #1057
state: Florida
city: Plantation
country: United States
facility: Investigator Site #1090
state: Florida
city: Tampa
country: United States
facility: Investigator Site #1089
state: Florida
city: Atlanta
country: United States
facility: Investigator Site #1170
state: Georgia
city: College Park
country: United States
facility: Investigator Site #1052
state: Georgia
city: Burlington
country: United States
facility: Investigator Site #1077
state: Massachusetts
city: Lansing
country: United States
facility: Investigator Site #1092
state: Michigan
city: Chesterfield
country: United States
facility: Investigator Site #1204
state: Missouri
city: Las Vegas
country: United States
facility: Investigator site #1209
state: Nevada
city: Sparta
country: United States
facility: Investigator Site #1189
state: New Jersey
city: Albuquerque
country: United States
facility: Investigator Site #1101
state: New Mexico
city: Brooklyn
country: United States
facility: Investigator Site #1058
state: New York
city: New York
country: United States
facility: Investigator Site #1088
state: New York
city: Queens
country: United States
facility: Investigator Site #1175
state: New York
city: Charlotte
country: United States
facility: Investigator Site #1095
state: North Carolina
city: Charlotte
country: United States
facility: Investigator Site #1056
state: North Carolina
city: Charlotte
country: United States
facility: Investigator Site #1173
state: North Carolina
city: Philadelphia
country: United States
facility: Investigator Site #1171
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Investigator Site #1062
state: Pennsylvania
city: Memphis
country: United States
facility: Investigator Site #1044
state: Tennessee
city: Carrollton
country: United States
facility: Investigator Site #1195
state: Texas
city: Colleyville
country: United States
facility: Investigator Site #1049
state: Texas
city: Fort Worth
country: United States
facility: Investigator Site #1071
state: Texas
city: Houston
country: United States
facility: Investigator Site #1094
state: Texas
city: Houston
country: United States
facility: Investigator Site #1169
state: Texas
city: Houston
country: United States
facility: Investigator site #1178
state: Texas
city: Red Oak
country: United States
facility: Investigator Site #1187
state: Texas
city: San Antonio
country: United States
facility: Investigator site #1053
state: Texas
city: San Antonio
country: United States
facility: Investigator Site #1186
state: Texas
city: Spring
country: United States
facility: Investigator Site #1172
state: Texas
city: Tomball
country: United States
facility: Investigator Site #1194
state: Texas
city: Caba
country: Argentina
facility: Investigator Site #3012
state: Buenos Aires
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Investigator Site #3001
state: Buenos Aires
city: La Plata
country: Argentina
facility: Investigator Site #3016
state: Buenos Aires
city: San Miguel de Tucuman
country: Argentina
facility: Investigator Site #3009
state: Tucman
city: San Miguel De Tucumán
country: Argentina
facility: Investigator Site #3010
state: Tucman
city: San Miguel De Tucumán
country: Argentina
facility: Investigator Site #3015
state: Tucumán
city: Buenos Aires
country: Argentina
facility: Investigator Site #3023
city: Mendoza
country: Argentina
facility: Investigator Site #3008
city: Haskovo
country: Bulgaria
facility: Investigator Site #5603
city: Pleven
country: Bulgaria
facility: Investigator Site #5602
city: Plovdiv
country: Bulgaria
facility: Investigator Site #5525
city: Plovdiv
country: Bulgaria
facility: Investigator Site #5521
city: Ruse
country: Bulgaria
facility: Investigator Site #5529
city: Sofia
country: Bulgaria
facility: Investigator Site #5522
city: Sofia
country: Bulgaria
facility: Investigator Site #5547
city: Sofia
country: Bulgaria
facility: Investigator Site #5541
city: Providencia
country: Chile
facility: Investigator Site #3006
city: Santiago
country: Chile
facility: Investigator Site #3002
city: Barranquilla
country: Colombia
facility: Investigator Site #3019
city: Barranquilla
country: Colombia
facility: Investigator Site #3011
city: Bogotá
country: Colombia
facility: Investigator Site #3021
city: Bogotá
country: Colombia
facility: Investigator Site #3022
city: Cali
country: Colombia
facility: Investigator Site #3020
city: Chia
country: Colombia
facility: Investigator Site #3003
city: Medellín
country: Colombia
facility: Investigator Site #3014
city: Rijeka
country: Croatia
facility: Investigator Site #5542
city: Split
country: Croatia
facility: Investigator Site #5543
city: Aarhus
country: Denmark
facility: Investigator Site #4012
city: Køge
country: Denmark
facility: Investigator Site #4011
city: Tbilisi
country: Georgia
facility: Investigator Site #5516
city: Tbilisi
country: Georgia
facility: Investigator Site #5523
city: Tbilisi
country: Georgia
facility: Investigator Site #5538
city: Tbilisi
country: Georgia
facility: Investigator Site #5536
city: Tbilisi
country: Georgia
facility: Investigator Site #5534
city: Tbilisi
country: Georgia
facility: Investigator Site #5517
city: Kirchheim Unter Teck
country: Germany
facility: Investigator Site #4001
city: Koeln
country: Germany
facility: Investigator Site #4004
city: Leipzig
country: Germany
facility: Investigator Site #4003
city: Mainz
country: Germany
facility: Investigator Site #4005
city: Munich
country: Germany
facility: Investigator Site #4006
city: Debrecen
country: Hungary
facility: Investigator Site #5548
city: Gyula
country: Hungary
facility: Investigator Site #5544
city: New Delhi
country: India
facility: Investigator Site # 6015
state: Delhi
city: Ahmedabad
country: India
facility: Investigator Site #6005
city: Ahmedabad
country: India
facility: Investigator Site #6010
city: Ahmedabad
country: India
facility: Investigator Site #6016
city: Ahmedabad
country: India
facility: Investigator Site #6006
city: Bangalore
country: India
facility: Investigator Site #6001
city: Bengaluru
country: India
facility: Investigator Site #6009
city: Chandigarh
country: India
facility: Investigator Site #6012
city: Haryana
country: India
facility: Investigator Site #6004
city: Jaipur
country: India
facility: Investigator Site #6013
city: Lucknow
country: India
facility: Investigator Site #6011
city: Nagpur
country: India
facility: Investigator Site #6008
city: Pune
country: India
facility: Investigator Site #6014
city: Pune
country: India
facility: Investigator Site #6007
city: Surat
country: India
facility: Investigator Site #6002
city: Surat
country: India
facility: Investigator Site #6003
city: Namdong
country: Korea, Republic of
facility: Investigator Site #8002
state: Incheon
city: Anyang-si
country: Korea, Republic of
facility: Investigator Site #8007
city: Busan
country: Korea, Republic of
facility: Investigator Site #8004
city: Seoul
country: Korea, Republic of
facility: Investigator Site #8016
city: Seoul
country: Korea, Republic of
facility: Investigator Site #8019
city: Seoul
country: Korea, Republic of
facility: Investigator Site #8012
city: Chihuahua
country: Mexico
facility: Investigator Site #2501
city: Ciudad de Mexico
country: Mexico
facility: Investigator Site #2509
city: Ciudad de Mexico
country: Mexico
facility: Investigator Site #2503
city: Ciudad De Mexico
country: Mexico
facility: Investigator Site #2506
city: Cuauhtémoc
country: Mexico
facility: Investigator Site #2504
city: Guadalajara
country: Mexico
facility: Investigator Site #2502
city: Guadalajara
country: Mexico
facility: Investigator Site #2512
city: Guadalajara
country: Mexico
facility: Investigator Site #2507
city: Madero
country: Mexico
facility: Investigator Site #2508
city: Merida
country: Mexico
facility: Investigator Site #2516
city: Mexico City
country: Mexico
facility: Investigator Site #2514
city: Mérida
country: Mexico
facility: Investigator Site #2511
city: Naucalpan De Juárez
country: Mexico
facility: Investigator Site # 2517
city: Oaxaca
country: Mexico
facility: Investigator Site #2510
city: San Luis Potosí
country: Mexico
facility: Investigator Site #2505
city: Torreon
country: Mexico
facility: Investigator Site #2513
city: Lima
country: Peru
facility: Investigator Site #3013
city: Lima
country: Peru
facility: Investigator Site #3004
city: San Martin De Porres
country: Peru
facility: Investigator Site #3018
city: Santiago De Surco
country: Peru
facility: Investigator Site #3005
city: Trujillo
country: Peru
facility: Investigator Site #3017
city: Angeles City
country: Philippines
facility: Investigator Site #8003
city: Iloilo City
country: Philippines
facility: Investigator Site #8009
city: Lipa City
country: Philippines
facility: Investigator Site #8011
city: Manila
country: Philippines
facility: Investigator Site #8001
city: Manila
country: Philippines
facility: Investigator Site #8010
city: Manila
country: Philippines
facility: Investigator Site #8018
city: Quezon City
country: Philippines
facility: Investigator Site #8006
city: Bialystok
country: Poland
facility: Investigator Site #5519
city: Białystok
country: Poland
facility: Investigator Site #5546
city: Białystok
country: Poland
facility: Investigator Site #5518
city: Bydgoszcz
country: Poland
facility: Investigator Site #5531
city: Bytom
country: Poland
facility: Investigator Site #5520
city: Częstochowa
country: Poland
facility: Investigator Site #5539
city: Kraków
country: Poland
facility: Investigator Site #5533
city: Nadarzyn
country: Poland
facility: Investigator Site #5537
city: Poznan
country: Poland
facility: Investigator Site #5545
city: Sosnowiec
country: Poland
facility: Investigator Site #5535
city: Szczecin
country: Poland
facility: Investigator Site #5532
city: Warsaw
country: Poland
facility: Investigator Site #5527
city: Warszawa
country: Poland
facility: Investigator Site #5540
city: Wrocław
country: Poland
facility: Investigator Site #5528
city: Caguas
country: Puerto Rico
facility: Investigator site #3028
city: San Juan
country: Puerto Rico
facility: Investigator site #3029
city: Bucuresti
country: Romania
facility: Investigator Site #5530
city: Bucuresti
country: Romania
facility: Investigator Site #5549
city: Bucuresti
country: Romania
facility: Investigator Site #5526
city: A Coruña
country: Spain
facility: Investigator Site #4013
city: Alicante
country: Spain
facility: Investigator Site #4008
city: Barcelona
country: Spain
facility: Investigator Site #4007
city: Sevilla
country: Spain
facility: Investigator Site #4002
city: Valencia
country: Spain
facility: Investigator Site #4009
city: Chiayi City
country: Taiwan
facility: Investigator Site #8013
city: Kaohsiung City
country: Taiwan
facility: Investigator Site #8014
city: Taichung
country: Taiwan
facility: Investigator Site #8008
city: Taichung
country: Taiwan
facility: Investigator Site #8015
city: Taipei
country: Taiwan
facility: Investigator Site #8017
city: Leeds
country: United Kingdom
facility: Investigator Site #4017
city: London
country: United Kingdom
facility: Investigator Site #4015
city: London
country: United Kingdom
facility: Investigator Site #4016
city: Southampton
country: United Kingdom
facility: Investigator Site #4014
Study officials:
References: