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

Sponsor

Alumis Inc (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05966480

Collaborator

(none)

388

Enrollment

139

Locations

Arms

29.2

Anticipated Duration (Months)

2.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
SLE	Drug: ESK-001 Drug: Placebo	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

388 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jun 26, 2023

Anticipated Primary Completion Date :

May 1, 2025

Anticipated Study Completion Date :

Dec 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ESK-001 Dose Level 1 ESK-001 administered as an oral tablet	Drug: ESK-001 Oral tablet
Experimental: ESK-001 Dose Level 2 ESK-001 administered as an oral tablet	Drug: ESK-001 Oral tablet
Experimental: ESK-001 Dose Level 3 ESK-001 administered as an oral tablet	Drug: ESK-001 Oral tablet
Placebo Comparator: Placebo Placebo administered as an oral tablet	Drug: Placebo Oral tablet

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

To assess the safety and tolerability of multiple dose levels of ESK-001 [Week 48]
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.
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 corticosteroid use in patients at Week 48 [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.
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 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 compare the Lupus Low Disease Activity State (LLDAS) response between doses of ESK-001 and placebo at Week 48 [Week 48]
To compare the annualized flare rate through Week 48 [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]
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.
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]
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.
To compare disease-specific QoL between doses of ESK-001 and placebo [Week 48]
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.
To compare disease-specific QoL between doses of ESK-001 and placebo [Week 48]
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).
To compare disease-specific QoL between doses of ESK-001 and placebo [Week 48]
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).
To compare Fatigue measured by FACIT-F between doses of ESK-001 and placebo [Week 48]
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.
To compare patient global assessment of disease activity (PtGA) between doses of ESK-001 and placebo [Week 48]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigator Site #1046	Anniston	Alabama	United States	36207
2	Investigator Site #1050	Los Alamitos	California	United States	90720
3	Investigator Site #1061	Upland	California	United States	91786
4	Investigator Site #1048	Aventura	Florida	United States	33180
5	Investigator Site #1063	Avon Park	Florida	United States	33825
6	Investigator Site #1045	Clearwater	Florida	United States	33765
7	Investigator Site #1055	Coral Gables	Florida	United States	33134
8	Investigator Site #1051	DeBary	Florida	United States	32713
9	Investigator Site # 1067	Miami Lakes	Florida	United States	33014
10	Investigator Site #1060	Miami	Florida	United States	33136
11	Investigator Site #1057	Miami	Florida	United States	33176
12	Investigator Site #1052	College Park	Georgia	United States	30329
13	Investigator Site #1058	Brooklyn	New York	United States	11201
14	Investigator Site #1056	Charlotte	North Carolina	United States	28210
15	Investigator Site #1062	Pittsburgh	Pennsylvania	United States	15224
16	Investigator Site #1044	Memphis	Tennessee	United States	38119
17	Investigator Site #1049	Colleyville	Texas	United States	76034
18	Investigator Site #1071	Fort Worth	Texas	United States	76177
19	Investigator Site #3012	Caba	Buenos Aires	Argentina	C1425
20	Investigator Site #3001	Ciudad Autonoma de Buenos Aires	Buenos Aires	Argentina	C1221ADC
21	Investigator Site #3016	La Plata	Buenos Aires	Argentina	B1900
22	Investigator Site #3009	San Miguel de Tucuman	Tucman	Argentina	T4000BRD
23	Investigator Site #3010	San Miguel De Tucumán	Tucman	Argentina	T4000BRD
24	Investigator Site #3015	San Miguel De Tucumán	Tucumán	Argentina	T4000
25	Investigator Site #3023	Buenos Aires		Argentina	C1114 AAH
26	Investigator Site #3008	Mendoza		Argentina	M5500CPH
27	Investigator Site #5525	Plovdiv		Bulgaria	4003
28	Investigator Site #5521	Plovdiv		Bulgaria
29	Investigator Site #5529	Ruse		Bulgaria	7002
30	Investigator Site #5522	Sofia		Bulgaria	1407
31	Investigator Site #5547	Sofia		Bulgaria	1463
32	Investigator Site #5541	Sofia		Bulgaria	1750
33	Investigator Site #3006	Providencia		Chile	7510586
34	Investigator Site #3002	Santiago		Chile	75500587
35	Investigator Site #3019	Barranquilla		Colombia	11111
36	Investigator Site #3011	Barranquilla		Colombia	80020
37	Investigator Site #3021	Bogotá		Colombia	110221
38	Investigator Site #3022	Bogotá		Colombia	504
39	Investigator Site #3020	Cali		Colombia	760035
40	Investigator Site #3003	Chia		Colombia	250001
41	Investigator Site #3014	Medellín		Colombia	50034
42	Investigator Site #5542	Rijeka		Croatia	51000
43	Investigator Site #5543	Split		Croatia	21000
44	Investigator Site #4012	Aarhus		Denmark	8200
45	Investigator Site #4011	Køge		Denmark	4600
46	Investigator Site #5516	Tbilisi		Georgia	0168
47	Investigator Site #5523	Tbilisi		Georgia	102
48	Investigator Site #5538	Tbilisi		Georgia	112
49	Investigator Site #5536	Tbilisi		Georgia	114
50	Investigator Site #5534	Tbilisi		Georgia	180
51	Investigator Site #4010	Bad Bramstedt		Germany
52	Investigator Site #4001	Kirchheim Unter Teck		Germany	73230
53	Investigator Site #4004	Koeln		Germany	50937
54	Investigator Site #4003	Leipzig		Germany	4103
55	Investigator Site #4005	Mainz		Germany	55131
56	Investigator Site #4006	Munich		Germany	80336
57	Investigator Site #5548	Debrecen		Hungary	4032
58	Investigator Site #5544	Gyula		Hungary
59	Investigator Site # 6015	New Delhi	Delhi	India	110 029
60	Investigator Site #6005	Ahmedabad		India	380005
61	Investigator Site #6010	Ahmedabad		India	380006
62	Investigator Site #6006	Ahmedabad		India	380015
63	Investigator Site #6001	Bangalore		India	560034
64	Investigator Site #6009	Bengaluru		India	560010
65	Investigator Site #6012	Chandigarh		India	160012
66	Investigator Site #6004	Haryana		India	122001
67	Investigator Site #6013	Jaipur		India	302004
68	Investigator Site #6011	Lucknow		India	226014
69	Investigator Site #6008	Nagpur		India	440012
70	Investigator Site #6014	Pune		India	411007
71	Investigator Site #6007	Pune		India	411057
72	Investigator Site #6002	Surat		India	395001
73	Investigator Site #6003	Surat		India	395002
74	Investigator Site #8002	Namdong	Incheon	Korea, Republic of	21565
75	Investigator Site #8007	Anyang-si		Korea, Republic of	14068
76	Investigator Site #8004	Busan		Korea, Republic of	49241
77	Investigator Site #8016	Seoul		Korea, Republic of	3080
78	Investigator Site #8019	Seoul		Korea, Republic of	5030
79	Investigator Site #8012	Seoul		Korea, Republic of	6273
80	Investigator Site #2501	Chihuahua		Mexico	31000
81	Investigator Site #2509	Ciudad de Mexico		Mexico	14080
82	Investigator Site #2503	Ciudad de Mexico		Mexico	3720
83	Investigator Site #2506	Ciudad De Mexico		Mexico	6700
84	Investigator Site #2504	Cuauhtémoc		Mexico	6720
85	Investigator Site #2502	Guadalajara		Mexico	44160
86	Investigator Site #2512	Guadalajara		Mexico	44620
87	Investigator Site #2507	Guadalajara		Mexico	44650
88	Investigator Site #2508	Madero		Mexico	7760
89	Investigator Site #2516	Merida		Mexico	97070
90	Investigator Site #2514	Mexico City		Mexico	3100
91	Investigator Site #2511	Mérida		Mexico	97070
92	Investigator Site # 2517	Naucalpan De Juárez		Mexico	54769
93	Investigator Site #2510	Oaxaca		Mexico	68000
94	Investigator Site #2505	San Luis Potosí		Mexico	78213
95	Investigator Site #2513	Torreon		Mexico	27000
96	Investigator Site #3013	Lima		Peru	15047
97	Investigator Site #3004	Lima		Peru	15801
98	Investigator Site #3018	San Martin De Porres		Peru	15102
99	Investigator Site #3005	Santiago De Surco		Peru	15023
100	Investigator Site #3017	Trujillo		Peru	13001
101	Investigator Site #8003	Angeles City		Philippines
102	Investigator Site #8009	Iloilo City		Philippines
103	Investigator Site #8011	Lipa City		Philippines
104	Investigator Site #8001	Manila		Philippines
105	Investigator Site #8010	Manila		Philippines
106	Investigator Site #8018	Manila		Philippines
107	Investigator Site #8006	Quezon City		Philippines
108	Investigator Site #5519	Bialystok		Poland	15-077
109	Investigator Site #5546	Białystok		Poland	15-297
110	Investigator Site #5518	Białystok		Poland	15-707
111	Investigator Site #5531	Bydgoszcz		Poland	85-168
112	Investigator Site #5520	Bytom		Poland	41-902
113	Investigator Site #5539	Częstochowa		Poland	42-200
114	Investigator Site #5533	Kraków		Poland	30-363
115	Investigator Site #5537	Nadarzyn		Poland	05-830
116	Investigator Site #5545	Poznan		Poland	61-397
117	Investigator Site #5535	Sosnowiec		Poland	41-200
118	Investigator Site #5532	Szczecin		Poland	71-252
119	Investigator Site #5527	Warsaw		Poland	00-215
120	Investigator Site #5540	Warszawa		Poland	02-637
121	Investigator Site #5528	Wrocław		Poland	50-088
122	Investigator Site #5530	Bucuresti		Romania	11025
123	Investigator Site #5549	Bucuresti		Romania	11057
124	Investigator Site #5526	Bucuresti		Romania	11172
125	Investigator Site #5524	Târgu-Mureş		Romania	540096
126	Investigator Site #4013	A Coruña		Spain	15006
127	Investigator Site #4008	Alicante		Spain	3699
128	Investigator Site #4007	Barcelona		Spain	8035
129	Investigator Site #4002	Sevilla		Spain	41014
130	Investigator Site #4009	Valencia		Spain	46010
131	Investigator Site #8013	Chiayi City		Taiwan	622
132	Investigator Site #8014	Kaohsiung City		Taiwan	11490
133	Investigator Site #8008	Taichung		Taiwan	40201
134	Investigator Site #8015	Taichung		Taiwan	40447
135	Investigator Site #8017	Taipei		Taiwan	100
136	Investigator Site #4017	Leeds		United Kingdom	LS1 3EX
137	Investigator Site #4015	London		United Kingdom	NW1 2BU
138	Investigator Site #4016	London		United Kingdom	SE1 7RT
139	Investigator Site #4014	Southampton		United Kingdom	SO16 6YD