M32 Systemic lupus erythematosus Systemic lupus erythematosus
Conditions
Interventions
assigned to 1 of the 4 study arms (3 ESK-001 active + 1 placebo). - assigned to 1 of the 4 study arms (3 ESK-001 active + 1 placebo).
Sponsors
Alumis Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •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 Males or females, age 18 to 70 years, inclusive, at the time of informed consent Body mass index 18 to 40 kg/m2 and total body weight >40 kg (88 lbs) Adequate peripheral venous access Diagnosed with SLE =6 months prior to screening, fulfills the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) criteria at the time of screening, AND has at least one of the following: • Positive antinuclear antibody test at screening by immunofluorescent assay at the central laboratory with titer =1:80; • Elevated anti-dsDNA antibodies as determined by the central laboratory; • Elevated anti-Smith antibody at screening as determined by the central laboratory; or • C3 or C4 below the lower limit of normal as determined by the central laboratory. During screening and prior to first administration of study drug, Central Review Team’s confirmation of the following: SLEDAI-2K Criteria: At screening the SLEDAI-2K score of =6. “Clinical” SLEDAI-2K score of =4 points. The “Clinical” SLEDAI-2K is the SLEDAI-2K assessment score without the inclusion of points attributable to any urine or laboratory results including immunologic measures: o Includes points from the following clinical components: arthritis, myositis, rash, alopecia, mucosal ulcers, pleurisy, pericarditis, and vasculitis o Excludes points attributable to fever, an SLE headache, and organic brain syndrome • BILAG-2004 Index Level Criteria: At least 1 of the following: o BILAG-2004 Index level A disease in at least 1 body/organ system ? Excludes scores from Lupus Headache o BILAG-2004 Index level B disease in more than 1 body/organ system ? Excludes scores from Lupus Headache • PGA score of >1.0 on a 0 to 3 VAS at screening Clinical SLEDAI-2K score =4 points with skin involvement prior to first administration of study drug Currently receives at least 1 of the following: • 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). o If corticosteroid is the only medication used for SLE activity, the daily dose must have been =10 mg and =40 mg prednisone equivalent for a minimum of 8 weeks prior to screening, and stable =10 mg and =40 mg for at least 2 weeks prior to screening. • And/or antimalarial treatment (e.g., hydroxychloroquine, chloroquine, quinacrine), • And/or no more than 1 of the following conventional DMARDS: o Azathioprine =200 mg/day o Mycophenolate mofetil =2 g/day or mycophenolic acid =1.44 g/day o Oral, subcutaneous, or intramuscular (IM) methotrexate =20 mg/week. Negative serum ß-human chorionic gonadotropin (ß-hCG) test at screening (women of childbearing potential [WOCBP] only) • WOCBP must agree to adhere to highly effective methods of contraception for the entirety of the study and for 30 days after the last dose of study drug • Nonsterilized male patients who are sexually active with WOCBP must agree to use highly effective methods of contraception for the entirety of the study and for 90 days after the last dose of study drug At Day 1, prior to randomization • “Clinical” SLEDAI-2K score of =4 points • OC dose stable for at least 2 weeks • WOCBP must have a negative
Exclusion criteria
Exclusion criteria: 1. Any acute or chronic illness/condition or evidence of an unstable clinical condition that, in the Investigator’s judgment, will substantially increase the risk to the patient if he or she participates in the study Presence or history (within 1 year) of psychiatric disease that, in the Investigator's opinion, is likely to interfere with patient’s ability to provide informed consent, comply with study procedures, or place the patient at increased risk by participating in the study Current or history within 1 year of screening of alcohol or drug abuse (excluding cannabis) based on Investigator’s clinical judgment. Pregnant, lactating, or planning to get pregnant during the study period and for 1 month after study completion or discontinuation Patients with QTcF >450 msec on ECG at screening Unstable cardiovascular disease, defined as a recent clinical deterioration (eg, unstable angina, rapid atrial fibrillation) or a cardiac hospitalization within the last 3 months At screening, has any of the following laboratory abnormalities: • Absolute neutrophil count 3.5 g/g Patient has planned major surgery during the study period 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, 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 History of or current diagnosis of catastrophic antiphospholipid syndrome within 12 months prior to signing the ICF. Antiphospholipid syndrome adequately controlled by anticoagulant therapy (other than warfarin) for at least 3 months is acceptable. Positive antiphospholipid antibodies without clinical symptoms are not exclusionary. History of any recurrent non-SLE disease that required treatment with oral or parenteral corticosteroids for more than a total of 2 weeks within the last 52 weeks prior to signing the ICF. Treatment with corticosteroids for conditions that are not expected to recur (eg, poison ivy) is not excluded. Receipt of any Investigational Products (small molecule or biologic agent) within 3 months or
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| meeting all of the following criteria: o Reduction of all BILAG-2004 A to B/C/D and baseline BILAG-2004 B to C/D, and no BILAG-2004 worsening in other organ systems, as defined by =1 new BILAG-2004 A or =2 new BILAG2004 B at Week 48 o No worsening from baseline in SLE Disease Activity Index 2000 (SLEDAI-2K), where worsening is defined as an increase from baseline of >0 points in SLEDAI-2K at Week 48 o No worsening from baseline in physician’s assessment of patient lupus disease activity, where worsening is defined by an increase =0.30 points on a 3-point Physician’s Global Assessment (PGA) visual analogue scale (VAS) at Week 48 The estimand is the difference in proportions of treatment success between treatment conditions (doses of ESK-001 and placebo, regardless of discontinuation) in patients with moderate to severe SLE whereby treatment success is defined as response at Week 48 in BICLA without use of additional or alternative medications NAME OF THE RESULT: 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 PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: 48 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Difference between baseline (Day 1) and Week 48 in FACIT-F NAME OF THE RESULT: To compare Fatigue measured by FACIT-F between doses of ESK-001 and placebo PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: 48 weeks;meeting all of the following criteria: o Reduction of all BILAG-2004 A to B/C/D and baseline BILAG-2004 B to C/D, and no BILAG-2004 worsening in other organ systems, as defined by =1 new BILAG-2004 A or =2 new BILAG2004 B at Week 48 o No worsening from baseline in SLE Disease Activity Index 2000 (SLEDAI-2K), where worsening is defined as an increase from baseline of >0 points in SLEDAI-2K at Week 48 o No worsening from baseline in physician’s assessment of patient lupus disease activity, where worsening is defined by an increase =0.30 points on a 3-point Physician’s Global Assessment (PGA) visual analogue scale (VAS) at Week 48 The estimand is the difference in proportions of treatment success between treatment conditions (doses of ESK-001 and placebo, regardless of discontinuation) in patients with moderate to severe SLE whereby treatment success is defined as response at Week 48 in BICLA without use of additional or alternative medications NAME OF THE RESULT: 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 PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: 48 weeks;Incidence of treatment-emergent AEs (TEAEs) and SAEs, vital signs, physical examination, 12-lead ECG, and clinical laboratory tests (hematology, clinical chemistry, urinalysis) NAME OF THE RESULT: To assess the safety and tolerability of multiple dose levels of ESK-001 PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: 48 weeks;Composite endpoint SRI( | — |
Countries
Argentina, Bulgaria, Chile, Colombia, Croatia, Denmark, Georgia, Germany, Hungary, India, Korea South, Mexico, Peru, Philippines, Poland, Romania, Spain, Taiwan, United Kindgdom, United States
Contacts
Public ContactMILAGROS PATRICIA NAVARRETE
SYNEOS HEALTH PERU S.R.L.
Outcome results
None listed