A Phase 2 interventional study of Enpatoran low dose and Enpatoran medium dose in Systemic Lupus Erythematosus, sponsored by EMD Serono Research & Development Institute, Inc.. Completed at 153 sites in 22 countries. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2025-12-01.
Sponsored by EMD Serono Research & Development Institute, Inc. (part of Merck KGaA, Darmstadt, Germany) · Phase 2, Interventional, and Treatment
The purpose of this Proof of Concept (PoC) and Dose-finding (DF) basket study is to evaluate the efficacy and safety of orally administered Enpatoran over 24 weeks in systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE; subacute cutaneous lupus erythematosus [SCLE] and/or discoid lupus erythematosus [DLE]) participants in a randomized, double-blind, placebo-controlled, parallel, adaptive and dose-ranging setting. Study Duration: 33 weeks Visit Frequency: every 2 or 4 weeks Enpatoran is not available through an expanded access program.
1,207 studies on the registry are indexed under Lupus Erythematosus, Systemic; 405 are open to participants now.
This study's enrollment of 456 is above the median of 52 across 876 interventional studies indexed under Lupus Erythematosus, Systemic.
Browse Lupus Erythematosus, Systemic studies →EMD Serono Research & Development Institute, Inc. is the lead sponsor of 87 studies on the registry; 8 are open to participants now.
Of its 47 completed or terminated interventional studies of FDA-regulated products, 38 (81%) have results posted.
First submitted after EMD Serono Research & Development Institute, Inc. became part of Merck KGaA, Darmstadt, Germany.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants with CLE (active SCLE and/or DLE) or SLE with predominantly active lupus rash (Cutaneous Lupus Erythematosus Disease Area and Severity Index \[CLASI-A\] greater than or equal to \[\>=\] 8) will be enrolled in Cohort A to receive placebo matched to Enpatoran.
Drug: Placebo
Participants with CLE (active SCLE and/or DLE) or SLE with predominantly active lupus rash (CLASI-A \>= 8) will be enrolled in Cohort A to receive low dose of Enpatoran.
Drug: Enpatoran low dose
Participants with CLE (active SCLE and/or DLE) or SLE with predominantly active lupus rash (CLASI-A \>= 8) will be enrolled in Cohort A to receive medium dose of Enpatoran.
Drug: Enpatoran medium dose
Participants with CLE (active SCLE and/or DLE) or SLE with predominantly active lupus rash (CLASI-A \>= 8) will be enrolled in Cohort A to receive high dose of Enpatoran.
Drug: Enpatoran high dose
Participants with active SLE who have moderate to high systemic disease activity (British Isles Lupus Assessment Group \[BILAG A/2B\]) with 1 or 2 of the following: CLASI-A \>= 8 and/or Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) \>= 6 will be enrolled in Cohort B to receive placebo matched to Enpatoran .
Drug: Placebo
Participants with active SLE who have moderate to high systemic disease activity (BILAG A/2B) with 1 or 2 of the following: CLASI-A \>= 8 and/or SLEDAI \>= 6 will be enrolled in Cohort B to receive high dose of Enpatoran.
Drug: Enpatoran high dose
Participants with active SLE who have moderate to high systemic disease activity (BILAG A/2B) with 1 or 2 of the following: CLASI-A \>= 8 and/or SLEDAI \>= 6 will be enrolled in Cohort B to receive low dose of M5049.
Drug: Enpatoran low dose
Participants with active SLE who have moderate to high systemic disease activity (BILAG A/2B) with 1 or 2 of the following: CLASI-A \>= 8 and/or SLEDAI \>= 6 will be enrolled in Cohort B to receive medium dose of Enpatoran.
Drug: Enpatoran medium dose
Participants will receive film-coated tablets of Enpatoran at a low dose orally, twice daily (BID) up to 24 weeks.
Also known as: M5049
Participants will receive film-coated tablets of Enpatoran at a medium dose, orally, BID up to 24 weeks.
Also known as: M5049
Participants will receive film-coated tablets of Enpatoran at a high dose, orally, BID up to 24 weeks.
Also known as: M5049
Participants will receive placebo matched to Enpatoran up to 24 weeks.
Cohort A: Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index-A (CLASI-A) Total Score at Week 16
The CLASI (Cutaneous Lupus Erythematosus Disease Area and Severity Index) was a validated instrument used to assess disease activity (CLASI-A) and damage in lupus erythematosus. The activity scale included erythema, scale/hypertrophy, active alopecia, recent hair loss, and mucous membrane disease, while the damage scale measured dyspigmentation, atrophy, and scarring. CLASI-A scores ranged from 0 to 70, with mild, moderate, and severe disease corresponding to scores of 0-9, 10-20, and 21-70, respectively. Erythema and scale/hypertrophy sub-scores were computed across 13 body areas, with maximum scores of 39 and 26, respectively. The remaining 5 points reflected contributions from active alopecia (0-3), recent hair loss (0-1), and mucous membrane involvement (0-1), completing the total CLASI-A activity score. Directionality reflected worsening with higher scores and improvement with lower scores.
Time frame: Baseline, week 16
Cohort B: Number of Participants With British Isles Lupus Assessment Group (BILAG)-Based Composite Lupus Assessment (BICLA) Response at Week 24
BILAG-based BICLA response is defined as participants meeting all of the following criteria: 1. Improvement in baseline BILAG scores in all organ systems with moderate or severe disease activity-i.e., all grade A scores (severe disease requiring high-dose therapy) must improve to B (moderate), C (mild), or D (no activity); all grade B scores (moderate disease requiring moderate therapy) must improve to C or D; 2. No new BILAG A scores and no more than one new BILAG B score; 3. No worsening in total SLEDAI-2K score from baseline; 4. No significant deterioration (≤10%) in physician's global assessment; and 5. No treatment failure, defined as initiation of non-protocol therapy. Directionality is toward clinical improvement and disease stabilization.
Time frame: At Week 24
Cohort A and B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Events (AEs) of Special Interest
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether considered related to the medicinal product or protocol-specified procedure. Serious AE was defined AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAE was defined as events with onset date or worsening during the on-treatment period. TEAEs included serious TEAEs and non-serious TEAEs. Adverse events of special interest (AESI) are serious or non-serious AEs that are of clinical interest and were closely followed.
Time frame: From screening upto safety follow up period (up to approximately 33 weeks)
Cohort A and B: Number of Participants With Abnormal Laboratory Parameters
Laboratory parameters included hematology, biochemistry, Urinalysis, Renal Toxicity and Hepatotoxicity. Number of Participants with Abnormal laboratory parameters (severity of grade greater or equal to 3) were reported. Severity of grade 3 or higher TEAEs were graded using National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 toxicity grades, as follows: Grade 3 = Severe; Grade 4 = Life-threatening and Grade 5 = Death.
Time frame: From screening upto safety follow up period (up to approximately 33 weeks)
Cohort A and B: Number of Participants With Clinically Important Increases in QT Interval Corrected Using Fridericia's Formula (QTcF)
12-lead ECG recordings included rhythm, heart rate (as measured by RR interval), PR interval, QRS duration, and QT interval. The corrected QT interval (QTcF) was calculated using Fridericia's formula. 12-lead ECG recordings were obtained after the participants have rested for at least 10 minutes in semisupine position. Clinical importance was determined by the investigator. The number of participants with clinically important increases in QTCF findings were reported.
Time frame: From screening upto safety follow up period (up to approximately 33 weeks)
Cohort A and Cohort B: Change From Baseline in Cutaneous Lupus Activity Investigator's Global Assessment (CLA-IGA) Scale Score at Week 16 and Week 24
The Cutaneous Lupus Activity Investigator's Global Assessment (CLA-IGA) is a validated clinician-reported outcome measure used to assess disease severity in participants with cutaneous lupus erythematosus. It is based on a 5-point ordinal scale that evaluates overall lesion characteristics, where 0 indicates "clear" skin and 4 represents "severe" disease. The scale includes the following categories: 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), and 4 (severe).
Time frame: Baseline and at Week 16 and Week 24
Cohort A and Cohort B: Change From Baseline in Physician's Global Assessment of Cutaneous Lupus Disease Activity Score at Week 16 and 24
The Physician's Global Assessment of Disease Activity was recorded using the 100 millimeter horizontal Visual Analog Scale (VAS). The score reflects the clinician's integrated judgment based on clinical signs, symptoms, laboratory findings, and patient-reported outcomes. PGA is used to quantify disease severity and monitor treatment response over time. Physician rated participant's disease activity on a scale ranged from 0-100 millimeter (mm), where 0 indicated no disease activity and 100 represented maximum disease activity.
Time frame: Baseline and at Week 16 and Week 24
Cohort B: Number of Participants With Both BICLA Response and With Clinically Meaningful Corticosteroids (CS) Reduction
BICLA (BILAG-Based Composite Lupus Assessment) defines response as improvement in all baseline BILAG A scores to B, C, or D and all B scores to C or D, with no new A scores and no more than one new B score. Responders must also show no worsening in SLEDAI-2K or Physician's Global Assessment (defined as ≥0.3-point increase). Corticosteroid (CS) reduction is defined as a decrease in daily prednisone-equivalent dose from ≥10 mg at Day 1 to ≤5 mg by Week 12, sustained through Week 24. BILAG grades reflect disease severity: A = severe disease requiring high-dose therapy; B = moderate disease requiring moderate therapy; C = mild stable disease; D = no current activity.
Time frame: At week 24 (BICLA Response) and Day 1 upto Week 24 (CS Reductions)
Cohort A and B: Number of Participants With Clinically Meaningful Corticosteroids (CS) Reduction
CS reduction is defined as the reduction of daily prednisone-equivalent dose from \>= 10 mg at Day 1 to \<= 5 mg by the Week 12 visit and sustained through Week 24. The number of participants with Clinically Meaningful CS Reduction were reported.
Time frame: Day 1 up to Week 24
Cohort A: Number of Participants With CLA-IGA Score 0 or 1 at Week 16 and Week 24
The Cutaneous Lupus Activity Investigator's Global Assessment (CLA-IGA) is a validated clinician-reported outcome measure used to assess disease severity in participants with cutaneous lupus erythematosus. It is based on a 5-point ordinal scale that evaluates overall lesion characteristics, where 0 indicates "clear" skin and 4 represents "severe" disease. The scale includes the following categories: 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), and 4 (severe). The number of participants with CLA-IGA score 0 or 1 at Week 16 and Week 24 were reported.
Time frame: At Week 16 and Week 24
Cohort B: Number of Participants With Systemic Lupus Erythematosus Responder Index-4 (SRI-4) Response at Week 24
SRI-4 response was defined as \>= 4-point reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) total score, no new British Isles Lupus Assessment Group (BILAG) A and no more than 1 new BILAG B domain score, no worsening (less than 10 percent increase) from baseline in Physician's Global Assessment of Disease Activity (PGA) and no treatment failure. SLEDAI-2K assessment consists of 24 items with total score of 0(no symptoms) to 105 (presence of all defined symptoms) with higher scores representing increased disease activity. BILAG Index: assessing clinical signs, symptoms, or laboratory parameters related to Systemic Lupus Erythematosus (SLE), divided into 9 organ systems. For each organ system A=severe disease, B=moderate disease, C=mild stable disease, D=inactive, but previously active, E=inactive and never affected. The PGA assess disease activity on a visual analogue scale =from 0(very well) to 100(very poor).
Time frame: At Week 24
Cohort B: Number of Participants With Lupus Low Disease Activity State (LLDAS) Attainment at Week 24
Lupus Low Disease Activity State (LLDAS) Attainment at Week 24 is defined as meeting all of the following criteria at the specified time point: SLE Disease Activity Index 2000 (SLEDAI-2K) ≤4 with no activity in major organ systems, no new disease activity compared to the previous assessment, Physician's Global Assessment (PGA) ≤1, current prednisone dose ≤7.5 mg/day, and standard maintenance dosing of immunosuppressive therapies. The number of participants with LLDAS Attainment at Week 24 were reported.
Time frame: At Week 24
Cohort B: Number of Participants With Remission Attainment at Week 24
Remission attainment was defined as a Clinical Hybrid Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index score of 0, Physician's Global Assessment of Systemic Lupus Erythematosus \<0.5 (0-3 scale), daily prednisolone-equivalent dose ≤5 mg, and stable use of immunosuppressive therapies including biologics. Number of participants who attained remission was reported.
Time frame: At Week 24
Cohort B: Percentage of Participants With 50% Reduction in Baseline Tender and Swollen Count at Week 24
The 28-joint count questionnaire assesses 14 joints on each side (28 joints overall) for both tenderness and swelling. The outcome for the assessment of each joint can be "absent", "present", "replaced" or "unable to evaluate".Tender 28-joint count will be derived as the count of joints which are tender. Swollen 28-joint count will be derived as the count of joints which are swollen. The number of tender and swollen joints will be calculated as the count of joints which are both tender and swollen. Percentage of Participants with 50% Reduction in Baseline Tender and Swollen Count at Week 24 was reported.
Time frame: At Week 24
Cohort B: Time to First Moderate/Severe British Isles Lupus Assessment Group (BILAG) Flare
Time to First Moderate/Severe British Isles Lupus Assessment Group (BILAG) Flare is defined as the time from baseline to the first occurrence of moderate or severe disease activity, as measured by the BILAG Index. The BILAG Index assesses clinical signs, symptoms, and laboratory parameters related to systemic lupus erythematosus (SLE) across 9 organ systems. Each organ system is scored alphabetically: A (severe disease), B (moderate disease), C (mild stable disease), D (inactive but previously active), and E (inactive and never affected). A moderate/severe flare is defined as the presence of at least one new or worsening BILAG A score (severe disease activity) or two or more new or worsening BILAG B scores (moderate disease activity) in any organ system, compared to the previous visit. Time to First Moderate/Severe British Isles Lupus Assessment Group (BILAG) Flare was estimated via Kaplan-Meier method.
Time frame: Baseline (Day 1) through Week 24
Cohort B: Time to First Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Flare Index (SFI) Severe Flare
Time to First Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Flare Index (SFI) Severe Flare is defined as the time from baseline to the first occurrence of a severe flare, as measured by the SLEDAI Flare Index (SFI). A severe flare is characterized by a ≥12-point increase in the SLEDAI score from the previous visit, accompanied by a ≥2.5-point increase in the physician's global assessment (on a 0-3 visual analogue scale), and a change in treatment such as initiation of corticosteroids at a dose \>0.5 mg/kg/day and/or the addition of a new immunosuppressive agent. Time to First Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Flare Index (SFI) Severe Flare was estimated via Kaplan-Meier method.
Time frame: Baseline (Day 1) through Week 24
Cohort A and B: Change From Baseline in Skindex 29+3 Symptom Domain Score at Week 24
The Skindex 29+3 is a self-reported measure of skin-specific symptoms and functioning for CLE populations, and includes items from the Skindex-29, designed for use across dermatologic conditions, and 3 additional items specific for lupus. Subscale scores are generated for each of the 3 original domains of the Skindex-29 i.e., symptoms, functioning, and emotional well-being. For all subscale scores, higher scores indicate lower functioning/worse symptoms. The symptoms domain includes items measuring physical sensations such as itching, burning, stinging, and pain. Each item is rated on a 5-point Likert scale from 1 ("never") to 5 ("all the time"), and scores are transformed to a 0-100 scale, with higher scores indicating more severe symptoms.
Time frame: Baseline and at week 24
Cohort A and B: Change From Baseline in the Skindex 29+3 Functioning Domain Scores at Week 24
The Skindex 29+3 is a self-reported measure of skin-specific symptoms and functioning for CLE populations, and includes items from the Skindex-29, designed for use across dermatologic conditions, and 3 additional items specific for lupus. Subscale scores are generated for each of the 3 original domains of the Skindex-29 i.e., symptoms, functioning, and emotional well-being. For all subscale scores, higher scores indicate lower functioning/worse symptoms. The functioning domain assesses the impact of skin disease on daily activities, social interactions, and work. Items are rated on a 5-point Likert scale (1 = "never" to 5 = "all the time") and transformed to a 0-100 scale, where higher scores reflect greater impairment in functioning.
Time frame: Baseline and at Week 24
Cohort A and B: Change From Baseline in the Skindex 29+3 Emotion Domain Scores at Week 24
The Skindex 29+3 is a self-reported measure of skin-specific symptoms and functioning for CLE populations, and includes items from the Skindex-29, designed for use across dermatologic conditions, and 3 additional items specific for lupus. Subscale scores are generated for each of the 3 original domains of the Skindex-29 i.e., symptoms, functioning, and emotional well-being. For all subscale scores, higher scores indicate lower functioning/worse symptoms. The emotion domain of the Skindex-29+3 assesses the psychological impact of skin disease in individuals with cutaneous lupus erythematosus. It includes items that measure feelings such as embarrassment, frustration, anger, sadness, and worry related to skin symptoms. Each item is rated on a 5-point Likert scale from 1 ("never") to 5 ("all the time"), and scores are transformed to a 0-100 scale, with higher scores indicating greater emotional distress.
Time frame: Baseline and at Week 24
Cohort A and B: Change From Baseline in the Skindex 29+3 Lupus-Specific Domain Scores at Week 24
The Skindex-29+3 is a self-reported measure of skin-specific symptoms and functioning for CLE populations. It includes items from the Skindex-29, designed for use across dermatologic conditions, and 3 additional items specific to lupus. Subscale scores are generated for the 3 original domains: symptoms, functioning, and emotional well-being. For all subscales, higher scores indicate worse symptoms or lower functioning. The lupus-specific domain captures symptoms and concerns unique to cutaneous lupus, including sensitivity to sunlight, flares from environmental exposure, and emotional impact of lupus-related skin changes. Each item is rated on a 5-point Likert scale from 1 ("never") to 5 ("all the time"), and scores are transformed to a 0-100 scale. Higher scores reflect greater symptom burden and disease impact.
Time frame: Baseline and at Week 24
Cohort A and B: Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scores at Week 24
Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) is a 13-item, self-reported questionnaire designed to assess fatigue and its impact on daily activities and functioning in individuals with chronic illness, including systemic lupus erythematosus. Each item is rated on a 5-point Likert-type scale ranging from 0 = "not at all" to 4 = "very much". Items are scored to ensure that 0 represents the worst and 4 the best possible outcome. The score ranges from 0 to 52, with higher scores indicating less fatigue and better functioning.
Time frame: Baseline and at Week 24
| Milestone | Cohort A: Placebo | Cohort A: Enpatoran 25 mg | Cohort A: Enpatoran 50 mg | Cohort A: Enpatoran 100 mg | Cohort B (Part 1 + Part 2): Placebo | Cohort B (Part 2): Enpatoran 25 mg | Cohort B (Part 2): Enpatoran 50 mg | Cohort B (Part 1 + Part 2): Enpatoran 100 mg |
|---|---|---|---|---|---|---|---|---|
| Started | 26 | 24 | 26 | 26 | 95 | 71 | 74 | 114 |
| Participants with bilag≥1a/2b randomized in error due to systemic disease activity | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 0 |
| Cohort b part 1 | 0 | 0 | 0 | 0 | 20 | 0 | 0 | 40 |
| Cohort b part 2 | 0 | 0 | 0 | 0 | 74 | 71 | 74 | 74 |
| Completed | 22 | 23 | 25 | 24 | 79 | 64 | 65 | 104 |
| Not completed | 4 | 1 | 1 | 2 | 16 | 7 | 9 | 10 |
| Withdrew: Other | 0 | 0 | 0 | 0 | 1 | 0 | 2 | 2 |
| Withdrew: Lack of efficacy | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 |
| Withdrew: Lost to follow-up | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 2 |
| Withdrew: Non-compliance | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 1 |
| Withdrew: Withdrawal by subject | 2 | 0 | 0 | 0 | 7 | 6 | 2 | 2 |
| Withdrew: Adverse event | 2 | 0 | 1 | 2 | 4 | 1 | 5 | 2 |
The CLASI (Cutaneous Lupus Erythematosus Disease Area and Severity Index) was a validated instrument used to assess disease activity (CLASI-A) and damage in lupus erythematosus. The activity scale included erythema, scale/hypertrophy, active alopecia, recent hair loss, and mucous membrane disease, while the damage scale measured dyspigmentation, atrophy, and scarring. CLASI-A scores ranged from 0 to 70, with mild, moderate, and severe disease corresponding to scores of 0-9, 10-20, and 21-70, respectively. Erythema and scale/hypertrophy sub-scores were computed across 13 body areas, with maximum scores of 39 and 26, respectively. The remaining 5 points reflected contributions from active alopecia (0-3), recent hair loss (0-1), and mucous membrane involvement (0-1), completing the total CLASI-A activity score. Directionality reflected worsening with higher scores and improvement with lower scores.
| scores on a scale | Cohort A: Placebo | Cohort A: Enpatoran 25 mg | Cohort A: Enpatoran 50 mg | Cohort A: Enpatoran 100 mg |
|---|---|---|---|---|
| Cohort A: Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index-A (CLASI-A) Total Score at Week 16 | -5.0 ± 3.94 | -9.0 ± 4.60 | -10.2 ± 6.77 | -9.7 ± 5.84 |
BILAG-based BICLA response is defined as participants meeting all of the following criteria: 1. Improvement in baseline BILAG scores in all organ systems with moderate or severe disease activity-i.e., all grade A scores (severe disease requiring high-dose therapy) must improve to B (moderate), C (mild), or D (no activity); all grade B scores (moderate disease requiring moderate therapy) must improve to C or D; 2. No new BILAG A scores and no more than one new BILAG B score; 3. No worsening in total SLEDAI-2K score from baseline; 4. No significant deterioration (≤10%) in physician's global assessment; and 5. No treatment failure, defined as initiation of non-protocol therapy. Directionality is toward clinical improvement and disease stabilization.
| Participants | Cohort B (Part 1 + Part 2): Placebo | Cohort B (Part 2): Enpatoran 25 mg | Cohort B (Part 2): Enpatoran 50 mg | Cohort B (Part 1 + Part 2): Enpatoran 100 mg |
|---|---|---|---|---|
| Cohort B: Number of Participants With British Isles Lupus Assessment Group (BILAG)-Based Composite Lupus Assessment (BICLA) Response at Week 24 | 37 | 41 | 36 | 56 |
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether considered related to the medicinal product or protocol-specified procedure. Serious AE was defined AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAE was defined as events with onset date or worsening during the on-treatment period. TEAEs included serious TEAEs and non-serious TEAEs. Adverse events of special interest (AESI) are serious or non-serious AEs that are of clinical interest and were closely followed.
| Participants | Cohort A: Placebo | Cohort A: Enpatoran 25 mg | Cohort A: Enpatoran 50 mg | Cohort A: Enpatoran 100 mg | Cohort B (Part 1 + Part 2): Placebo | Cohort B (Part 2): Enpatoran 25 mg | Cohort B (Part 2): Enpatoran 50 mg | Cohort B (Part 1 + Part 2): Enpatoran 100 mg |
|---|---|---|---|---|---|---|---|---|
| TEAEs | 12 | 15 | 15 | 21 | 61 | 42 | 47 | 70 |
| Serious TEAEs | 1 | 2 | 0 | 1 | 3 | 1 | 3 | 5 |
| AESI | 0 | 0 | 0 | 2 | 3 | 1 | 0 | 3 |
Laboratory parameters included hematology, biochemistry, Urinalysis, Renal Toxicity and Hepatotoxicity. Number of Participants with Abnormal laboratory parameters (severity of grade greater or equal to 3) were reported. Severity of grade 3 or higher TEAEs were graded using National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 toxicity grades, as follows: Grade 3 = Severe; Grade 4 = Life-threatening and Grade 5 = Death.
| Participants | Cohort A: Placebo | Cohort A: Enpatoran 25 mg | Cohort A: Enpatoran 50 mg | Cohort A: Enpatoran 100 mg | Cohort B (Part 1 + Part 2): Placebo | Cohort B (Part 2): Enpatoran 25 mg | Cohort B (Part 2): Enpatoran 50 mg | Cohort B (Part 1 + Part 2): Enpatoran 100 mg |
|---|---|---|---|---|---|---|---|---|
| Cohort A and B: Number of Participants With Abnormal Laboratory Parameters | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
12-lead ECG recordings included rhythm, heart rate (as measured by RR interval), PR interval, QRS duration, and QT interval. The corrected QT interval (QTcF) was calculated using Fridericia's formula. 12-lead ECG recordings were obtained after the participants have rested for at least 10 minutes in semisupine position. Clinical importance was determined by the investigator. The number of participants with clinically important increases in QTCF findings were reported.
| Participants | Cohort A: Placebo | Cohort A: Enpatoran 25 mg | Cohort A: Enpatoran 50 mg | Cohort A: Enpatoran 100 mg | Cohort B (Part 1 + Part 2): Placebo | Cohort B (Part 2): Enpatoran 25 mg | Cohort B (Part 2): Enpatoran 50 mg | Cohort B (Part 1 + Part 2): Enpatoran 100 mg |
|---|---|---|---|---|---|---|---|---|
| Cohort A and B: Number of Participants With Clinically Important Increases in QT Interval Corrected Using Fridericia's Formula (QTcF) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
The Cutaneous Lupus Activity Investigator's Global Assessment (CLA-IGA) is a validated clinician-reported outcome measure used to assess disease severity in participants with cutaneous lupus erythematosus. It is based on a 5-point ordinal scale that evaluates overall lesion characteristics, where 0 indicates "clear" skin and 4 represents "severe" disease. The scale includes the following categories: 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), and 4 (severe).
| units on a scale | Cohort A: Placebo | Cohort A: Enpatoran 25 mg | Cohort A: Enpatoran 50 mg | Cohort A: Enpatoran 100 mg | Cohort B (Part 1 + Part 2): Placebo | Cohort B (Part 2): Enpatoran 25 mg | Cohort B (Part 2): Enpatoran 50 mg | Cohort B (Part 1 + Part 2): Enpatoran 100 mg |
|---|---|---|---|---|---|---|---|---|
| Baseline | 3.0 ± 0.66 | 3.0 ± 0.714 | 3.0 ± 0.61 | 3.179 ± 0.59 | 2.8 ± 0.72 | 2.9 ± 0.67 | 2.7 ± 0.65 | 2.8 ± 0.57 |
| Week 16 | -0.9 ± 1.01 | -1.7 ± 1.09 | -1.5 ± 1.14 | -1.8 ± 0.88 | -0.6 ± 0.96 | -1.1 ± 1.15 | -1.2 ± 1.01 | -1.5 ± 1.00 |
| Week 24 | -0.9 ± 1.17 | -1.8 ± 0.92 | -1.7 ± 0.92 | -2.1 ± 1.08 | -0.8 ± 1.00 | -1.5 ± 1.19 | -1.4 ± 0.94 | -1.8 ± 0.98 |
The Physician's Global Assessment of Disease Activity was recorded using the 100 millimeter horizontal Visual Analog Scale (VAS). The score reflects the clinician's integrated judgment based on clinical signs, symptoms, laboratory findings, and patient-reported outcomes. PGA is used to quantify disease severity and monitor treatment response over time. Physician rated participant's disease activity on a scale ranged from 0-100 millimeter (mm), where 0 indicated no disease activity and 100 represented maximum disease activity.
| millimeter | Cohort A: Placebo | Cohort A: Enpatoran 25 mg | Cohort A: Enpatoran 50 mg | Cohort A: Enpatoran 100 mg | Cohort B (Part 1 + Part 2): Placebo | Cohort B (Part 2): Enpatoran 25 mg | Cohort B (Part 2): Enpatoran 50 mg | Cohort B (Part 1 + Part 2): Enpatoran 100 mg |
|---|---|---|---|---|---|---|---|---|
| Baseline | 61.4 ± 14.08 | 61.8 ± 15.37 | 56.3 ± 19.42 | 61.7 ± 18.04 | 55.7 ± 17.08 | 56.1 ± 15.65 | 56.7 ± 14.85 | 57.4 ± 17.42 |
| Week 16 | -25.3 ± 20.55 | -42.5 ± 23.67 | -35.2 ± 25.70 | -42.0 ± 22.94 | -16.7 ± 20.01 | -26.1 ± 17.62 | -30.7 ± 22.78 | -36.0 ± 22.08 |
| Week 24 | -23.9 ± 25.45 | -44.0 ± 21.97 | -41.2 ± 25.12 | -49.1 ± 22.44 | -21.3 ± 18.35 | -33.0 ± 19.68 | -34.8 ± 20.06 | -39.1 ± 23.16 |
BICLA (BILAG-Based Composite Lupus Assessment) defines response as improvement in all baseline BILAG A scores to B, C, or D and all B scores to C or D, with no new A scores and no more than one new B score. Responders must also show no worsening in SLEDAI-2K or Physician's Global Assessment (defined as ≥0.3-point increase). Corticosteroid (CS) reduction is defined as a decrease in daily prednisone-equivalent dose from ≥10 mg at Day 1 to ≤5 mg by Week 12, sustained through Week 24. BILAG grades reflect disease severity: A = severe disease requiring high-dose therapy; B = moderate disease requiring moderate therapy; C = mild stable disease; D = no current activity.
| Participants | Cohort B (Part 1 + Part 2): Placebo | Cohort B (Part 2): Enpatoran 25 mg | Cohort B (Part 2): Enpatoran 50 mg | Cohort B (Part 1 + Part 2): Enpatoran 100 mg |
|---|---|---|---|---|
| Cohort B: Number of Participants With Both BICLA Response and With Clinically Meaningful Corticosteroids (CS) Reduction | 16 | 20 | 20 | 28 |
CS reduction is defined as the reduction of daily prednisone-equivalent dose from \>= 10 mg at Day 1 to \<= 5 mg by the Week 12 visit and sustained through Week 24. The number of participants with Clinically Meaningful CS Reduction were reported.
| Participants | Cohort A: Placebo | Cohort A: Enpatoran 25 mg | Cohort A: Enpatoran 50 mg | Cohort A: Enpatoran 100 mg | Cohort B (Part 1 + Part 2): Placebo | Cohort B (Part 2): Enpatoran 25 mg | Cohort B (Part 2): Enpatoran 50 mg | Cohort B (Part 1 + Part 2): Enpatoran 100 mg |
|---|---|---|---|---|---|---|---|---|
| Cohort A and B: Number of Participants With Clinically Meaningful Corticosteroids (CS) Reduction | 6 | 7 | 12 | 9 | 36 | 28 | 27 | 41 |
The Cutaneous Lupus Activity Investigator's Global Assessment (CLA-IGA) is a validated clinician-reported outcome measure used to assess disease severity in participants with cutaneous lupus erythematosus. It is based on a 5-point ordinal scale that evaluates overall lesion characteristics, where 0 indicates "clear" skin and 4 represents "severe" disease. The scale includes the following categories: 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), and 4 (severe). The number of participants with CLA-IGA score 0 or 1 at Week 16 and Week 24 were reported.
| Participants | Cohort A: Placebo | Cohort A: Enpatoran 25 mg | Cohort A: Enpatoran 50 mg | Cohort A: Enpatoran 100 mg |
|---|---|---|---|---|
| Week 16 | 4 | 10 | 10 | 12 |
| Week 24 | 7 | 11 | 12 | 14 |
SRI-4 response was defined as \>= 4-point reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) total score, no new British Isles Lupus Assessment Group (BILAG) A and no more than 1 new BILAG B domain score, no worsening (less than 10 percent increase) from baseline in Physician's Global Assessment of Disease Activity (PGA) and no treatment failure. SLEDAI-2K assessment consists of 24 items with total score of 0(no symptoms) to 105 (presence of all defined symptoms) with higher scores representing increased disease activity. BILAG Index: assessing clinical signs, symptoms, or laboratory parameters related to Systemic Lupus Erythematosus (SLE), divided into 9 organ systems. For each organ system A=severe disease, B=moderate disease, C=mild stable disease, D=inactive, but previously active, E=inactive and never affected. The PGA assess disease activity on a visual analogue scale =from 0(very well) to 100(very poor).
| Participants | Cohort B (Part 1 + Part 2): Placebo | Cohort B (Part 2): Enpatoran 25 mg | Cohort B (Part 2): Enpatoran 50 mg | Cohort B (Part 1 + Part 2): Enpatoran 100 mg |
|---|---|---|---|---|
| Cohort B: Number of Participants With Systemic Lupus Erythematosus Responder Index-4 (SRI-4) Response at Week 24 | 50 | 44 | 48 | 77 |
Lupus Low Disease Activity State (LLDAS) Attainment at Week 24 is defined as meeting all of the following criteria at the specified time point: SLE Disease Activity Index 2000 (SLEDAI-2K) ≤4 with no activity in major organ systems, no new disease activity compared to the previous assessment, Physician's Global Assessment (PGA) ≤1, current prednisone dose ≤7.5 mg/day, and standard maintenance dosing of immunosuppressive therapies. The number of participants with LLDAS Attainment at Week 24 were reported.
| Participants | Cohort B (Part 1 + Part 2): Placebo | Cohort B (Part 2): Enpatoran 25 mg | Cohort B (Part 2): Enpatoran 50 mg | Cohort B (Part 1 + Part 2): Enpatoran 100 mg |
|---|---|---|---|---|
| Cohort B: Number of Participants With Lupus Low Disease Activity State (LLDAS) Attainment at Week 24 | 23 | 21 | 32 | 35 |
Remission attainment was defined as a Clinical Hybrid Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index score of 0, Physician's Global Assessment of Systemic Lupus Erythematosus \<0.5 (0-3 scale), daily prednisolone-equivalent dose ≤5 mg, and stable use of immunosuppressive therapies including biologics. Number of participants who attained remission was reported.
| Participants | Cohort B (Part 1 + Part 2): Placebo | Cohort B (Part 2): Enpatoran 25 mg | Cohort B (Part 2): Enpatoran 50 mg | Cohort B (Part 1 + Part 2): Enpatoran 100 mg |
|---|---|---|---|---|
| Cohort B: Number of Participants With Remission Attainment at Week 24 | 10 | 7 | 8 | 20 |
The 28-joint count questionnaire assesses 14 joints on each side (28 joints overall) for both tenderness and swelling. The outcome for the assessment of each joint can be "absent", "present", "replaced" or "unable to evaluate".Tender 28-joint count will be derived as the count of joints which are tender. Swollen 28-joint count will be derived as the count of joints which are swollen. The number of tender and swollen joints will be calculated as the count of joints which are both tender and swollen. Percentage of Participants with 50% Reduction in Baseline Tender and Swollen Count at Week 24 was reported.
| percentage of participants | Cohort B (Part 1 + Part 2): Placebo | Cohort B (Part 2): Enpatoran 25 mg | Cohort B (Part 2): Enpatoran 50 mg | Cohort B (Part 1 + Part 2): Enpatoran 100 mg |
|---|---|---|---|---|
| Cohort B: Percentage of Participants With 50% Reduction in Baseline Tender and Swollen Count at Week 24 | 68.8 | 72.2 | 77.6 | 79.1 |
Time to First Moderate/Severe British Isles Lupus Assessment Group (BILAG) Flare is defined as the time from baseline to the first occurrence of moderate or severe disease activity, as measured by the BILAG Index. The BILAG Index assesses clinical signs, symptoms, and laboratory parameters related to systemic lupus erythematosus (SLE) across 9 organ systems. Each organ system is scored alphabetically: A (severe disease), B (moderate disease), C (mild stable disease), D (inactive but previously active), and E (inactive and never affected). A moderate/severe flare is defined as the presence of at least one new or worsening BILAG A score (severe disease activity) or two or more new or worsening BILAG B scores (moderate disease activity) in any organ system, compared to the previous visit. Time to First Moderate/Severe British Isles Lupus Assessment Group (BILAG) Flare was estimated via Kaplan-Meier method.
| days | Cohort B (Part 1 + Part 2): Placebo | Cohort B (Part 2): Enpatoran 25 mg | Cohort B (Part 2): Enpatoran 50 mg | Cohort B (Part 1 + Part 2): Enpatoran 100 mg |
|---|---|---|---|---|
| Cohort B: Time to First Moderate/Severe British Isles Lupus Assessment Group (BILAG) Flare | NA (NA to NA) | NA (NA to NA) | NA (NA to NA) | NA (NA to NA) |
Time to First Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Flare Index (SFI) Severe Flare is defined as the time from baseline to the first occurrence of a severe flare, as measured by the SLEDAI Flare Index (SFI). A severe flare is characterized by a ≥12-point increase in the SLEDAI score from the previous visit, accompanied by a ≥2.5-point increase in the physician's global assessment (on a 0-3 visual analogue scale), and a change in treatment such as initiation of corticosteroids at a dose \>0.5 mg/kg/day and/or the addition of a new immunosuppressive agent. Time to First Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Flare Index (SFI) Severe Flare was estimated via Kaplan-Meier method.
| days | Cohort B (Part 1 + Part 2): Placebo | Cohort B (Part 2): Enpatoran 25 mg | Cohort B (Part 2): Enpatoran 50 mg | Cohort B (Part 1 + Part 2): Enpatoran 100 mg |
|---|---|---|---|---|
| Cohort B: Time to First Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Flare Index (SFI) Severe Flare | NA (NA to NA) | NA (NA to NA) | NA (NA to NA) | NA (NA to NA) |
The Skindex 29+3 is a self-reported measure of skin-specific symptoms and functioning for CLE populations, and includes items from the Skindex-29, designed for use across dermatologic conditions, and 3 additional items specific for lupus. Subscale scores are generated for each of the 3 original domains of the Skindex-29 i.e., symptoms, functioning, and emotional well-being. For all subscale scores, higher scores indicate lower functioning/worse symptoms. The symptoms domain includes items measuring physical sensations such as itching, burning, stinging, and pain. Each item is rated on a 5-point Likert scale from 1 ("never") to 5 ("all the time"), and scores are transformed to a 0-100 scale, with higher scores indicating more severe symptoms.
| scores on a scale | Cohort A: Placebo | Cohort A: Enpatoran 25 mg | Cohort A: Enpatoran 50 mg | Cohort A: Enpatoran 100 mg | Cohort B (Part 1 + Part 2): Placebo | Cohort B (Part 2): Enpatoran 25 mg | Cohort B (Part 2): Enpatoran 50 mg | Cohort B (Part 1 + Part 2): Enpatoran 100 mg |
|---|---|---|---|---|---|---|---|---|
| Cohort A and B: Change From Baseline in Skindex 29+3 Symptom Domain Score at Week 24 | -13.7 (-21.4 to -6.1) | -27.3 (-34.7 to -19.9) | -28.6 (-36.1 to -21.2) | -21.9 (-28.8 to -14.9) | -9.2 (-16.5 to -2.0) | -17.5 (-25.9 to -9.2) | -15.2 (-22.6 to -7.9) | -17.0 (-23.5 to -10.5) |
The Skindex 29+3 is a self-reported measure of skin-specific symptoms and functioning for CLE populations, and includes items from the Skindex-29, designed for use across dermatologic conditions, and 3 additional items specific for lupus. Subscale scores are generated for each of the 3 original domains of the Skindex-29 i.e., symptoms, functioning, and emotional well-being. For all subscale scores, higher scores indicate lower functioning/worse symptoms. The functioning domain assesses the impact of skin disease on daily activities, social interactions, and work. Items are rated on a 5-point Likert scale (1 = "never" to 5 = "all the time") and transformed to a 0-100 scale, where higher scores reflect greater impairment in functioning.
| scores on a scale | Cohort A: Placebo | Cohort A: Enpatoran 25 mg | Cohort A: Enpatoran 50 mg | Cohort A: Enpatoran 100 mg | Cohort B (Part 1 + Part 2): Placebo | Cohort B (Part 2): Enpatoran 25 mg | Cohort B (Part 2): Enpatoran 50 mg | Cohort B (Part 1 + Part 2): Enpatoran 100 mg |
|---|---|---|---|---|---|---|---|---|
| Cohort A and B: Change From Baseline in the Skindex 29+3 Functioning Domain Scores at Week 24 | -12.2 (-19.5 to -4.8) | -17.9 (-24.9 to -10.8) | -20.3 (-27.4 to -13.1) | -15.1 (-21.7 to -8.5) | -11.1 (-18.4 to -3.8) | -14.2 (-23.0 to -5.5) | -11.3 (-18.7 to -3.8) | -15.4 (-22.0 to -8.9) |
The Skindex 29+3 is a self-reported measure of skin-specific symptoms and functioning for CLE populations, and includes items from the Skindex-29, designed for use across dermatologic conditions, and 3 additional items specific for lupus. Subscale scores are generated for each of the 3 original domains of the Skindex-29 i.e., symptoms, functioning, and emotional well-being. For all subscale scores, higher scores indicate lower functioning/worse symptoms. The emotion domain of the Skindex-29+3 assesses the psychological impact of skin disease in individuals with cutaneous lupus erythematosus. It includes items that measure feelings such as embarrassment, frustration, anger, sadness, and worry related to skin symptoms. Each item is rated on a 5-point Likert scale from 1 ("never") to 5 ("all the time"), and scores are transformed to a 0-100 scale, with higher scores indicating greater emotional distress.
| scores on a scale | Cohort A: Placebo | Cohort A: Enpatoran 25 mg | Cohort A: Enpatoran 50 mg | Cohort A: Enpatoran 100 mg | Cohort B (Part 1 + Part 2): Placebo | Cohort B (Part 2): Enpatoran 25 mg | Cohort B (Part 2): Enpatoran 50 mg | Cohort B (Part 1 + Part 2): Enpatoran 100 mg |
|---|---|---|---|---|---|---|---|---|
| Cohort A and B: Change From Baseline in the Skindex 29+3 Emotion Domain Scores at Week 24 | -15.8 (-25.3 to -6.4) | -23.1 (-32.3 to -13.9) | -21.2 (-30.5 to -12.0) | -23.2 (-31.8 to -14.5) | -15.3 (-24.6 to -6.0) | -18.0 (-29.1 to -6.8) | -16.9 (-26.3 to -7.4) | -16.3 (-24.6 to -7.9) |
The Skindex-29+3 is a self-reported measure of skin-specific symptoms and functioning for CLE populations. It includes items from the Skindex-29, designed for use across dermatologic conditions, and 3 additional items specific to lupus. Subscale scores are generated for the 3 original domains: symptoms, functioning, and emotional well-being. For all subscales, higher scores indicate worse symptoms or lower functioning. The lupus-specific domain captures symptoms and concerns unique to cutaneous lupus, including sensitivity to sunlight, flares from environmental exposure, and emotional impact of lupus-related skin changes. Each item is rated on a 5-point Likert scale from 1 ("never") to 5 ("all the time"), and scores are transformed to a 0-100 scale. Higher scores reflect greater symptom burden and disease impact.
| scores on a scale | Cohort A: Placebo | Cohort A: Enpatoran 25 mg | Cohort A: Enpatoran 50 mg | Cohort A: Enpatoran 100 mg | Cohort B (Part 1 + Part 2): Placebo | Cohort B (Part 2): Enpatoran 25 mg | Cohort B (Part 2): Enpatoran 50 mg | Cohort B (Part 1 + Part 2): Enpatoran 100 mg |
|---|---|---|---|---|---|---|---|---|
| Cohort A and B: Change From Baseline in the Skindex 29+3 Lupus-Specific Domain Scores at Week 24 | -15.5 (-26.8 to -4.3) | -19.9 (-30.6 to -9.1) | -21.1 (-31.9 to -10.3) | -11.0 (-21.1 to -1.0) | -16.4 (-26.8 to -6.0) | -10.9 (-23.1 to 1.3) | -13.1 (-23.8 to -2.4) | -14.5 (-23.8 to -5.2) |
Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) is a 13-item, self-reported questionnaire designed to assess fatigue and its impact on daily activities and functioning in individuals with chronic illness, including systemic lupus erythematosus. Each item is rated on a 5-point Likert-type scale ranging from 0 = "not at all" to 4 = "very much". Items are scored to ensure that 0 represents the worst and 4 the best possible outcome. The score ranges from 0 to 52, with higher scores indicating less fatigue and better functioning.
| scores on a scale | Cohort A: Placebo | Cohort A: Enpatoran 25 mg | Cohort A: Enpatoran 50 mg | Cohort A: Enpatoran 100 mg | Cohort B (Part 1 + Part 2): Placebo | Cohort B (Part 2): Enpatoran 25 mg | Cohort B (Part 2): Enpatoran 50 mg | Cohort B (Part 1 + Part 2): Enpatoran 100 mg |
|---|---|---|---|---|---|---|---|---|
| Cohort A and B: Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scores at Week 24 | 3.0 (0.3 to 5.8) | 2.0 (-0.7 to 4.7) | 6.9 (4.2 to 9.6) | 4.3 (1.7 to 6.8) | 2.4 (0.4 to 4.4) | 4.8 (2.5 to 7.0) | 3.6 (1.4 to 5.8) | 5.1 (3.3 to 6.9) |
Collected over From screening up to safety follow up period (up to approximately 33 weeks). Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Cohort A: Placebo | 0/26 (0%) | 1/26 (3.8%) | 8/26 (30.8%) |
| Cohort A: Enpatoran 25 mg | 0/24 (0%) | 2/24 (8.3%) | 4/24 (16.7%) |
| Cohort A: Enpatoran 50 mg | 0/26 (0%) | 0/26 (0%) | 6/26 (23.1%) |
| Cohort A: Enpatoran 100 mg | 0/26 (0%) | 1/26 (3.8%) | 13/26 (50%) |
| Cohort B (Part 1 + Part 2): Placebo | 0/95 (0%) | 3/95 (3.2%) | 29/95 (30.5%) |
| Cohort B (Part 2): Enpatoran 25 mg | 0/71 (0%) | 1/71 (1.4%) | 17/71 (23.9%) |
| Cohort B (Part 2): Enpatoran 50 mg | 0/74 (0%) | 3/74 (4.1%) | 24/74 (32.4%) |
| Cohort B (Part 1 + Part 2): Enpatoran 100 mg | 0/114 (0%) | 5/114 (4.4%) | 33/114 (28.9%) |
| Event | Cohort A: Placebo | Cohort A: Enpatoran 25 mg | Cohort A: Enpatoran 50 mg | Cohort A: Enpatoran 100 mg | Cohort B (Part 1 + Part 2): Placebo | Cohort B (Part 2): Enpatoran 25 mg | Cohort B (Part 2): Enpatoran 50 mg | Cohort B (Part 1 + Part 2): Enpatoran 100 mg |
|---|---|---|---|---|---|---|---|---|
| Humerus fractureInjury, poisoning and procedural complications | 0/26 | 1/24 | 0/26 | 0/26 | 0/95 | 0/71 | 0/74 | 0/114 |
| Multiple injuriesInjury, poisoning and procedural complications | 0/26 | 1/24 | 0/26 | 0/26 | 0/95 | 0/71 | 0/74 | 0/114 |
| Sternal fractureInjury, poisoning and procedural complications | 0/26 | 1/24 | 0/26 | 0/26 | 0/95 | 0/71 | 0/74 | 0/114 |
| Herpes zosterInfections and infestations | 0/26 | 0/24 | 0/26 | 1/26 | 0/95 | 0/71 | 0/74 | 0/114 |
| Invasive ductal breast carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 1/26 | 0/24 | 0/26 | 0/26 | 0/95 | 0/71 | 0/74 | 1/114 |
| PneumoniaInfections and infestations | 0/26 | 0/24 | 0/26 | 0/26 | 1/95 | 0/71 | 0/74 | 2/114 |
| Radius fractureInjury, poisoning and procedural complications | 0/26 | 0/24 | 0/26 | 0/26 | 0/95 | 1/71 | 0/74 | 0/114 |
| Peripheral nerve injuryInjury, poisoning and procedural complications | 0/26 | 0/24 | 0/26 | 0/26 | 0/95 | 0/71 | 1/74 | 0/114 |
| Skin injuryInjury, poisoning and procedural complications | 0/26 | 0/24 | 0/26 | 0/26 | 0/95 | 0/71 | 1/74 | 0/114 |
| Upper limb fractureInjury, poisoning and procedural complications | 0/26 | 0/24 | 0/26 | 0/26 | 0/95 | 0/71 | 1/74 | 0/114 |
| Event | Cohort A: Placebo | Cohort A: Enpatoran 25 mg | Cohort A: Enpatoran 50 mg | Cohort A: Enpatoran 100 mg | Cohort B (Part 1 + Part 2): Placebo | Cohort B (Part 2): Enpatoran 25 mg | Cohort B (Part 2): Enpatoran 50 mg | Cohort B (Part 1 + Part 2): Enpatoran 100 mg |
|---|---|---|---|---|---|---|---|---|
| Upper respiratory tract infectionInfections and infestations | 2/26 | 2/24 | 4/26 | 5/26 | 6/95 | 7/71 | 9/74 | 8/114 |
| Urinary tract infectionInfections and infestations | 4/26 | 0/24 | 0/26 | 2/26 | 8/95 | 0/71 | 5/74 | 11/114 |
| HeadacheNervous system disorders | 2/26 | 2/24 | 2/26 | 0/26 | 0/95 | 0/71 | 7/74 | 0/114 |
| NasopharyngitisInfections and infestations | 2/26 | 0/24 | 0/26 | 0/26 | 0/95 | 0/71 | 6/74 | 10/114 |
| DiarrhoeaGastrointestinal disorders | 0/26 | 0/24 | 2/26 | 2/26 | 7/95 | 4/71 | 0/74 | 0/114 |
| Abdominal pain upperGastrointestinal disorders | 2/26 | 0/24 | 0/26 | 2/26 | 0/95 | 0/71 | 0/74 | 0/114 |
| Herpes zosterInfections and infestations | 0/26 | 0/24 | 0/26 | 2/26 | 0/95 | 0/71 | 0/74 | 0/114 |
| Alanine aminotransferase increasedInvestigations | 0/26 | 0/24 | 0/26 | 2/26 | 0/95 | 0/71 | 0/74 | 0/114 |
| Aspartate aminotransferase increasedInvestigations | 0/26 | 0/24 | 0/26 | 2/26 | 0/95 | 0/71 | 0/74 | 0/114 |
| Blood creatinine increasedInvestigations | 0/26 | 0/24 | 0/26 | 2/26 | 0/95 | 0/71 | 0/74 | 0/114 |
The Full Analysis Set (FAS) included all participants randomized in the cohort to which they were eligible. Participants who were randomized in error were excluded from FAS.
| Age, Continuous(years) | Cohort A: Placebo | Cohort A: Enpatoran 25 mg | Cohort A: Enpatoran 50 mg | Cohort A: Enpatoran 100 mg | Cohort B (Part 1 + Part 2): Placebo | Cohort B (Part 2): Enpatoran 25 mg | Cohort B (Part 2): Enpatoran 50 mg | Cohort B (Part 1 + Part 2): Enpatoran 100 mg | Total |
|---|---|---|---|---|---|---|---|---|---|
| Mean | 49 ± 11.0 | 42 ± 12.1 | 47 ± 14.6 | 45 ± 14.3 | 42 ± 12.3 | 42 ± 12.4 | 39 ± 12.3 | 44 ± 12.2 | 42 ± 12.3 |
| Sex: Female, Male(Participants) | Cohort A: Placebo | Cohort A: Enpatoran 25 mg | Cohort A: Enpatoran 50 mg | Cohort A: Enpatoran 100 mg | Cohort B (Part 1 + Part 2): Placebo | Cohort B (Part 2): Enpatoran 25 mg | Cohort B (Part 2): Enpatoran 50 mg | Cohort B (Part 1 + Part 2): Enpatoran 100 mg | Total |
|---|---|---|---|---|---|---|---|---|---|
| Female | 22 | 17 | 19 | 19 | 87 | 69 | 69 | 110 | 412 |
| Male | 4 | 6 | 6 | 7 | 7 | 2 | 5 | 4 | 41 |
| Ethnicity (NIH/OMB)(Participants) | Cohort A: Placebo | Cohort A: Enpatoran 25 mg | Cohort A: Enpatoran 50 mg | Cohort A: Enpatoran 100 mg | Cohort B (Part 1 + Part 2): Placebo | Cohort B (Part 2): Enpatoran 25 mg | Cohort B (Part 2): Enpatoran 50 mg | Cohort B (Part 1 + Part 2): Enpatoran 100 mg | Total |
|---|---|---|---|---|---|---|---|---|---|
| Hispanic or Latino | 10 | 9 | 11 | 11 | 47 | 37 | 37 | 51 | 213 |
| Not Hispanic or Latino | 16 | 14 | 14 | 15 | 47 | 34 | 37 | 63 | 240 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Cohort A: Placebo | Cohort A: Enpatoran 25 mg | Cohort A: Enpatoran 50 mg | Cohort A: Enpatoran 100 mg | Cohort B (Part 1 + Part 2): Placebo | Cohort B (Part 2): Enpatoran 25 mg | Cohort B (Part 2): Enpatoran 50 mg | Cohort B (Part 1 + Part 2): Enpatoran 100 mg | Total |
|---|---|---|---|---|---|---|---|---|---|
| American Indian or Alaska Native | 4 | 3 | 2 | 3 | 27 | 22 | 18 | 28 | 107 |
| Asian | 7 | 8 | 9 | 8 | 26 | 16 | 20 | 27 | 121 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 4 | 1 | 2 | 1 | 3 | 6 | 6 | 3 | 26 |
| White | 11 | 11 | 12 | 14 | 35 | 24 | 29 | 51 | 187 |
| More than one race | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 2 | 3 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 2 | 3 | 1 | 3 | 9 |
Showing the first 100 of 153 sites across 22 countries. Choose a country and city above to see the rest.
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21
Supporting information: Study protocol, Statistical analysis plan, Clinical study report, Analytic code
Time frame: Within six months after the approval of a new product or a new indication for an approved product in both the United States and the European Union
Access criteria: Qualified scientific and medical researchers can request the data. Such requests must be submitted in writing to the company's portal and will be internally reviewed regarding criteria for researchers' qualification and legitimacy of the research proposal.
Data sharing details ↗ · bit.ly
This study is completed, as verified in Nov 2025. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Enpatoran
Lupus Erythematosus, Systemic →
EMD Serono Research & Development Institute, Inc. →