Systemic Lupus Erythematosus
Conditions
Keywords
Musculoskeletal and connective tissue disorders
Brief summary
The purpose of the study is to assess the efficacy and safety of 4 doses of cenerimod versus placebo in adult subjects with systemic lupus erythematosus (SLE).
Detailed description
This is a Phase 2b, multicenter, multinational, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of 4 doses of cenerimod versus placebo in adult subjects with moderately to severely active, autoantibody-positive systemic lupus erythematosus (SLE).
Interventions
DRUGCenerimod 0.5 mg
Cenerimod will be supplied as a film-coated tablets at the dose of 0.5 mg
DRUGCenerimod 1 mg
Cenerimod will be supplied as a film-coated tablets at the dose of 1 mg
DRUGCenerimod 2 mg
Cenerimod will be supplied as a film-coated tablets at the dose of 2 mg
DRUGCenerimod 4 mg
Cenerimod will be supplied as a film-coated tablets at the dose of 4 mg
DRUGPlacebo
Matching placebo will be supplied as identical film-coated tablets formulated with the same excipients but without the active ingredient, cenerimod
DRUGcenerimod 2 mg (ex-4 mg)
Cenerimod will be supplied as a film-coated tablets at the dose of 2 mg
Sponsors
Viatris Innovation GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Participants randomized to the 4 mg arm who are still on treatment at month 6 will be re-randomized in a 1:1 ratio to placebo or cenerimod 2 mg to enter Treatment Period 2 and will continue study treatment for a total maximum of 12 months.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Signed Informed Consent Form prior to any study-mandated procedure * Diagnosis of SLE made at least 6 months prior to Screening, by fulfilling at least 4 of the 11 criteria for SLE as defined by the American College of Rheumatology (ACR) criteria * A mSLEDAI-2K score ≥ 6 of at least 2 points for musculoskeletal or mucocutaneous manifestations (i.e., myositis, arthritis, rash, alopecia, mucosal ulcers). * Currently treated with stable doses of one or more of the following background medications: * NSAIDs * Anti-malarials (≤ 400 mg/day hydroxychloroquine, ≤ 500 mg/day chloroquine, ≤ 100 mg/day quinacrine) * Mycophenolate mofetil (≤ 2 g/day) * Mycophenolic acid (≤ 1440 mg/day) * Azathioprine (≤ 2 mg/kg/day) * Methotrexate (≤ 20 mg/week) * Corticosteroids (≤ 40 mg/day prednisone or equivalent) * Belimumab (≤10 mg/kg every 4 weeks intravenously, or 200 mg/week subcutaneously). * History or presence of positive autoantibodies measured by central laboratory defined as follows: (a) Positive antinuclear antibody (ANA) test measured by immunofluorescence assay (IFA) with titre ≥1:80; AND/OR (b) positive anti-double stranded deoxyribonucleic acid (anti-dsDNA) antibodies with titre ≥30 IU/mL * Women of childbearing potential: * Must have a negative serum pregnancy test at Screening * Must agree to undertake monthly urine pregnancy tests during the study * Must use highly effective methods of contraception from the screening visit until 6 months after taking the last dose of study treatment.
Exclusion criteria
* Active lupus nephritis or a renal biopsy demonstrating immune complex mediated glomerulonephritis compatible with lupus nephritis. * CNS (Central Nervous System) lupus and severe forms of vasculitis requiring systemic immunosuppressive treatment * A diagnosis of mixed connective tissue disease or any history of overlap syndromes of SLE with rheumatoid arthritis, erosive arthritis, scleroderma or autoimmune hepatitis * History or presence of Mobitz type II or third-degree atrioventricular block, sick sinus syndrome, symptomatic bradycardia or syncope associated with cardiac disorders * Subjects who experienced myocardial infarction, unstable angina pectoris, stroke, transient ischemic attack, vascular thrombosis, decompensated heart failure requiring hospitalization, or heart failure defined by the New York Heart Association Class III/IV within six months prior to Screening * An elevated QT corrected for HR (Heart Rate) on the basis of Fridericia's formula interval of \> 470 ms (females) / \> 450 ms (males) * History or presence of severe respiratory disease or pulmonary fibrosis * Active or latent tuberculosis * Ongoing bacterial, viral or fungal infection that is of clinical concern in the judgment of the investigator or history of any serious infection * Subjects who have congenital or acquired severe immunodeficiency or known HIV infection or positive HIV testing * Presence of macular edema or active uveitis * Type 1 or 2 diabetes that is poorly controlled according to investigator judgment, or diabetes complicated with organ involvement such as diabetic nephropathy or retinopathy * Significant hematology abnormality: Lymphocyte count \< 800 /μL (0.8 × 10e9/L); hemoglobin \< 9 g/dL; WBC (White Blood Cell) count \< 2500/μL (2.5 × 10e9/L) or platelets \< 75000/μL (75 × 10e9/L) * Estimated glomerular filtration rate \< 60 mL/min/1.73 m2 * Known allergy to S1P (sphingosine-1-phosphate) receptor modulators or any of the cenerimod formulation excipients
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Month 6 in the Modified Systemic Lupus Erythematosus Activity Index 2000 (mSLEDAI-2K) Score | Baseline (Day 1) and Month 6 | The primary endpoint is the absolute change from baseline in the modified Systemic Lupus Erythematosus Activity Index 2000 (mSLEDAI-2K) score. The SLEDAI-2K is a cumulative index of lupus disease activity scored by the physician. It is calculated from 24 individual descriptors across 9 organ systems, with weighted scores of 2-8, and measures disease activity within the last 10 days. 0 points indicates inactive disease, and 105 points is the maximum possible score. In this study the SLEDAI-2K was modified, to exclude leucopenia (minus 1 point), due to the mechanism of action of cenerimod. Improvement in systemic lupus erythematosus disease activity is defined as a reduction in SLEDAI-2K score of greater than or equal to 4. A decreased score, i.e., a negative change, indicates an improvement in systemic lupus erythematosus disease activity from baseline to Month 6. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response on Systemic Lupus Erythematosus Responder Index 4 (SRI-4) at Month 6 as Compared to Baseline | Baseline (Day 1) and Month 6 | A responder could only be assessed if the full information of all body systems was available. A participant was defined as a responder based on the Systemic Lupus Erythematosus Responder Index 4 (SRI-4) was a composite, binary endpoint based on three variables: * mSLEDAI-2K score had to have a reduction from baseline greater than or equal to 4, * Physician Global Assessment (PGA) had to have an increase from baseline less than or equal to 0.3. The PGA is a 100 mm visual analog scale used by the physician to assess disease activity ranging for 0 to 3. The scale is anchored with values from 0 = "none" and 3 = "severe"), and * BILAG-2004 (no new BILAG A organ domain score and at most one new BILAG B organ domain score) compared with baseline. If one of the SRI-4 mSLEDAI-2K, PGA and BILAG variables were not met the subject was scored a non-responder. Participants that did not fit at least one of the above criteria were assigned to the missing group. |
| British Isles Lupus Assessment Group-2004 (BILAG) Disease Activity Index Response at Month 6 | Baseline (Day 1) and Month 6 | The British Isles Lupus Assessment Group-2004 (BILAG) is a comprehensive tool used by the physician to assess disease activity and is sensitive to small changes over time. Response (no worsening) at Month 6 on BILAG-2004 disease activity index was defined as no new BILAG A organ domain score and no more than one new BILAG B organ domain score compared with baseline. No analysis is reported because the model did not meet the convergence criteria. |
Countries
Bulgaria, Chile, Czechia, France, Georgia, Germany, Greece, Hungary, Israel, Italy, Japan, Mexico, Philippines, Poland, Puerto Rico, Romania, Russia, Spain, Taiwan, Thailand, Turkey (Türkiye), Ukraine, United Kingdom, United States
Contacts
STUDY_DIRECTORClinical Trials
Viatris Innovation GmbH
Participant flow
Recruitment details
The study was done from 21 December 2018 to 25 August 2022.
Pre-assignment details
427 participants are considered to be enrolled in the study and were randomized to study treatment. This represents the Full Analysis Set (treatment as assigned). 810 adult subjects with SLE have been screened and 427 subjects randomized in a 1:1:1:1:1 ratio to placebo, 0.5, 1, 2, or 4 mg once daily (o.d.) of cenerimod, in addition to background SLE therapy.
Participants by arm
| Arm | Count |
|---|---|
| Cenerimod 0.5 mg Participants were randomized to receive cenerimod 0.5 mg once daily in addition to background SLE therapy for up to 6 months in Treatment Period 1. | 85 |
| Cenerimod 1 mg Participants were randomized to receive cenerimod 1 mg once daily in addition to background SLE therapy for up to 6 months in Treatment Period 1. | 85 |
| Cenerimod 2 mg Participants were randomized to receive cenerimod 2 mg once daily in addition to background SLE therapy for up to 6 months in Treatment Period 1. | 86 |
| Cenerimod 4 mg Participants were randomized to receive cenerimod 4 mg once daily in addition to background SLE therapy for up to 6 months in Treatment Period 1. | 85 |
| Placebo Participants were randomized to receive placebo once daily in addition to background SLE therapy for up to 6 months in Treatment Period 1. | 86 |
| Total | 427 |
Baseline characteristics
| Characteristic | Total | Cenerimod 0.5 mg | Cenerimod 1 mg | Cenerimod 2 mg | Cenerimod 4 mg | Placebo |
|---|---|---|---|---|---|---|
| Age, Continuous | 41.6 years STANDARD_DEVIATION 11.94 | 42.8 years STANDARD_DEVIATION 12.41 | 40.0 years STANDARD_DEVIATION 12.77 | 42.2 years STANDARD_DEVIATION 12.06 | 42.1 years STANDARD_DEVIATION 10.44 | 41.0 years STANDARD_DEVIATION 11.94 |
| Age, Customized Between 18 and 45 years | 259 years | 49 years | 54 years | 49 years | 50 years | 57 years |
| Age, Customized Between 45 and 64 years | 156 years | 31 years | 29 years | 36 years | 33 years | 27 years |
| Age, Customized Between 64 and 75 years | 12 years | 5 years | 2 years | 1 years | 2 years | 2 years |
| Body Mass Index | 26.14 kilograms/square meter STANDARD_DEVIATION 6.33 | 25.67 kilograms/square meter STANDARD_DEVIATION 5.67 | 25.55 kilograms/square meter STANDARD_DEVIATION 5.95 | 26.16 kilograms/square meter STANDARD_DEVIATION 6.6 | 26.82 kilograms/square meter STANDARD_DEVIATION 7.15 | 26.49 kilograms/square meter STANDARD_DEVIATION 6.24 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 89 Participants | 16 Participants | 17 Participants | 18 Participants | 19 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 336 Participants | 69 Participants | 68 Participants | 68 Participants | 65 Participants | 66 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| modified SLEDAI at baseline | 9.9 units on a scale STANDARD_DEVIATION 2.99 | 9.8 units on a scale STANDARD_DEVIATION 2.69 | 10.1 units on a scale STANDARD_DEVIATION 3.71 | 9.5 units on a scale STANDARD_DEVIATION 2.88 | 10.0 units on a scale STANDARD_DEVIATION 2.5 | 10.2 units on a scale STANDARD_DEVIATION 3.05 |
| Race (NIH/OMB) American Indian or Alaska Native | 18 Participants | 5 Participants | 3 Participants | 6 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 33 Participants | 5 Participants | 9 Participants | 7 Participants | 6 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 33 Participants | 3 Participants | 6 Participants | 8 Participants | 10 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) White | 337 Participants | 72 Participants | 67 Participants | 65 Participants | 65 Participants | 68 Participants |
| Region of Enrollment Bulgaria | 13 participants | 5 participants | 2 participants | 1 participants | 3 participants | 2 participants |
| Region of Enrollment Chile | 18 participants | 1 participants | 3 participants | 2 participants | 5 participants | 7 participants |
| Region of Enrollment Czechia | 7 participants | 2 participants | 2 participants | 2 participants | 0 participants | 1 participants |
| Region of Enrollment France | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants |
| Region of Enrollment Georgia | 15 participants | 5 participants | 3 participants | 1 participants | 4 participants | 2 participants |
| Region of Enrollment Greece | 1 participants | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants |
| Region of Enrollment Israel | 2 participants | 0 participants | 1 participants | 1 participants | 0 participants | 0 participants |
| Region of Enrollment Italy | 4 participants | 1 participants | 1 participants | 0 participants | 1 participants | 1 participants |
| Region of Enrollment Mexico | 39 participants | 10 participants | 6 participants | 10 participants | 6 participants | 7 participants |
| Region of Enrollment Philippines | 27 participants | 4 participants | 7 participants | 6 participants | 5 participants | 5 participants |
| Region of Enrollment Poland | 21 participants | 6 participants | 2 participants | 3 participants | 3 participants | 7 participants |
| Region of Enrollment Romania | 2 participants | 1 participants | 0 participants | 0 participants | 1 participants | 0 participants |
| Region of Enrollment Russia | 24 participants | 2 participants | 8 participants | 7 participants | 5 participants | 2 participants |
| Region of Enrollment Spain | 7 participants | 1 participants | 2 participants | 0 participants | 0 participants | 4 participants |
| Region of Enrollment Taiwan | 2 participants | 0 participants | 0 participants | 1 participants | 1 participants | 0 participants |
| Region of Enrollment Thailand | 2 participants | 0 participants | 2 participants | 0 participants | 0 participants | 0 participants |
| Region of Enrollment Turkey | 1 participants | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants |
| Region of Enrollment Ukraine | 150 participants | 36 participants | 29 participants | 29 participants | 27 participants | 29 participants |
| Region of Enrollment United Kingdom | 3 participants | 0 participants | 0 participants | 0 participants | 2 participants | 1 participants |
| Region of Enrollment United States | 88 participants | 11 participants | 17 participants | 21 participants | 21 participants | 18 participants |
| Sex: Female, Male Female | 406 Participants | 79 Participants | 83 Participants | 80 Participants | 82 Participants | 82 Participants |
| Sex: Female, Male Male | 21 Participants | 6 Participants | 2 Participants | 6 Participants | 3 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 84 | 2 / 85 | 0 / 87 | 0 / 35 | 0 / 35 | 0 / 14 | 0 / 86 |
| other Total, other adverse events | 37 / 84 | 54 / 85 | 53 / 87 | 23 / 35 | 20 / 35 | 13 / 14 | 39 / 86 |
| serious Total, serious adverse events | 4 / 84 | 12 / 85 | 4 / 87 | 1 / 35 | 0 / 35 | 2 / 14 | 6 / 86 |
Outcome results
Primary
Change From Baseline to Month 6 in the Modified Systemic Lupus Erythematosus Activity Index 2000 (mSLEDAI-2K) Score
The primary endpoint is the absolute change from baseline in the modified Systemic Lupus Erythematosus Activity Index 2000 (mSLEDAI-2K) score. The SLEDAI-2K is a cumulative index of lupus disease activity scored by the physician. It is calculated from 24 individual descriptors across 9 organ systems, with weighted scores of 2-8, and measures disease activity within the last 10 days. 0 points indicates inactive disease, and 105 points is the maximum possible score. In this study the SLEDAI-2K was modified, to exclude leucopenia (minus 1 point), due to the mechanism of action of cenerimod. Improvement in systemic lupus erythematosus disease activity is defined as a reduction in SLEDAI-2K score of greater than or equal to 4. A decreased score, i.e., a negative change, indicates an improvement in systemic lupus erythematosus disease activity from baseline to Month 6.
Time frame: Baseline (Day 1) and Month 6
Population: Full Analysis Set (FAS).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Cenerimod 0.5 mg | Change From Baseline to Month 6 in the Modified Systemic Lupus Erythematosus Activity Index 2000 (mSLEDAI-2K) Score | -3.2 score on a scale |
| Cenerimod 1 mg | Change From Baseline to Month 6 in the Modified Systemic Lupus Erythematosus Activity Index 2000 (mSLEDAI-2K) Score | -3.41 score on a scale |
| Cenerimod 2 mg | Change From Baseline to Month 6 in the Modified Systemic Lupus Erythematosus Activity Index 2000 (mSLEDAI-2K) Score | -2.84 score on a scale |
| Cenerimod 4 mg | Change From Baseline to Month 6 in the Modified Systemic Lupus Erythematosus Activity Index 2000 (mSLEDAI-2K) Score | -4.04 score on a scale |
| Placebo | Change From Baseline to Month 6 in the Modified Systemic Lupus Erythematosus Activity Index 2000 (mSLEDAI-2K) Score | -2.85 score on a scale |
Comparison: The analysis was performed on the Full Analysis Set (FAS). The FAS included all participants who were randomized. Baseline was defined as the last measurement before randomization.p-value: 0.474995% CI: [-1.45, 0.68]Mixed Models Analysis
Comparison: The analysis was performed on the Full Analysis Set (FAS). The FAS included all participants who were randomized. Baseline was defined as the last measurement before randomization.p-value: 0.294195% CI: [-1.65, 0.49]Mixed Models Analysis
Comparison: The analysis was performed on the Full Analysis Set (FAS). The FAS included all participants who were randomized. Baseline was defined as the last measurement before randomization.p-value: 0.980295% CI: [-1.05, 1.08]Mixed Models Analysis
Comparison: The analysis was performed on the Full Analysis Set (FAS). The FAS included all participants who were randomized. Baseline was defined as the last measurement before randomization.p-value: 0.029195% CI: [-2.25, -0.12]Mixed Models Analysis
Secondary
British Isles Lupus Assessment Group-2004 (BILAG) Disease Activity Index Response at Month 6
The British Isles Lupus Assessment Group-2004 (BILAG) is a comprehensive tool used by the physician to assess disease activity and is sensitive to small changes over time. Response (no worsening) at Month 6 on BILAG-2004 disease activity index was defined as no new BILAG A organ domain score and no more than one new BILAG B organ domain score compared with baseline. No analysis is reported because the model did not meet the convergence criteria.
Time frame: Baseline (Day 1) and Month 6
Population: Full analysis set (FAS).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cenerimod 0.5 mg | British Isles Lupus Assessment Group-2004 (BILAG) Disease Activity Index Response at Month 6 | 98.8 percentage of participants |
| Cenerimod 1 mg | British Isles Lupus Assessment Group-2004 (BILAG) Disease Activity Index Response at Month 6 | 98.7 percentage of participants |
| Cenerimod 2 mg | British Isles Lupus Assessment Group-2004 (BILAG) Disease Activity Index Response at Month 6 | 97.5 percentage of participants |
| Cenerimod 4 mg | British Isles Lupus Assessment Group-2004 (BILAG) Disease Activity Index Response at Month 6 | 98.7 percentage of participants |
| Placebo | British Isles Lupus Assessment Group-2004 (BILAG) Disease Activity Index Response at Month 6 | 97.4 percentage of participants |
Secondary
Response on Systemic Lupus Erythematosus Responder Index 4 (SRI-4) at Month 6 as Compared to Baseline
A responder could only be assessed if the full information of all body systems was available. A participant was defined as a responder based on the Systemic Lupus Erythematosus Responder Index 4 (SRI-4) was a composite, binary endpoint based on three variables: * mSLEDAI-2K score had to have a reduction from baseline greater than or equal to 4, * Physician Global Assessment (PGA) had to have an increase from baseline less than or equal to 0.3. The PGA is a 100 mm visual analog scale used by the physician to assess disease activity ranging for 0 to 3. The scale is anchored with values from 0 = none and 3 = severe), and * BILAG-2004 (no new BILAG A organ domain score and at most one new BILAG B organ domain score) compared with baseline. If one of the SRI-4 mSLEDAI-2K, PGA and BILAG variables were not met the subject was scored a non-responder. Participants that did not fit at least one of the above criteria were assigned to the missing group.
Time frame: Baseline (Day 1) and Month 6
Population: Full Analysis Set (FAS)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cenerimod 0.5 mg | Response on Systemic Lupus Erythematosus Responder Index 4 (SRI-4) at Month 6 as Compared to Baseline | Missing | 4 participants |
| Cenerimod 0.5 mg | Response on Systemic Lupus Erythematosus Responder Index 4 (SRI-4) at Month 6 as Compared to Baseline | Non-responder | 45 participants |
| Cenerimod 0.5 mg | Response on Systemic Lupus Erythematosus Responder Index 4 (SRI-4) at Month 6 as Compared to Baseline | Responder | 36 participants |
| Cenerimod 1 mg | Response on Systemic Lupus Erythematosus Responder Index 4 (SRI-4) at Month 6 as Compared to Baseline | Non-responder | 38 participants |
| Cenerimod 1 mg | Response on Systemic Lupus Erythematosus Responder Index 4 (SRI-4) at Month 6 as Compared to Baseline | Responder | 41 participants |
| Cenerimod 1 mg | Response on Systemic Lupus Erythematosus Responder Index 4 (SRI-4) at Month 6 as Compared to Baseline | Missing | 6 participants |
| Cenerimod 2 mg | Response on Systemic Lupus Erythematosus Responder Index 4 (SRI-4) at Month 6 as Compared to Baseline | Missing | 7 participants |
| Cenerimod 2 mg | Response on Systemic Lupus Erythematosus Responder Index 4 (SRI-4) at Month 6 as Compared to Baseline | Responder | 38 participants |
| Cenerimod 2 mg | Response on Systemic Lupus Erythematosus Responder Index 4 (SRI-4) at Month 6 as Compared to Baseline | Non-responder | 41 participants |
| Cenerimod 4 mg | Response on Systemic Lupus Erythematosus Responder Index 4 (SRI-4) at Month 6 as Compared to Baseline | Non-responder | 36 participants |
| Cenerimod 4 mg | Response on Systemic Lupus Erythematosus Responder Index 4 (SRI-4) at Month 6 as Compared to Baseline | Responder | 41 participants |
| Cenerimod 4 mg | Response on Systemic Lupus Erythematosus Responder Index 4 (SRI-4) at Month 6 as Compared to Baseline | Missing | 8 participants |
| Placebo | Response on Systemic Lupus Erythematosus Responder Index 4 (SRI-4) at Month 6 as Compared to Baseline | Missing | 9 participants |
| Placebo | Response on Systemic Lupus Erythematosus Responder Index 4 (SRI-4) at Month 6 as Compared to Baseline | Responder | 34 participants |
| Placebo | Response on Systemic Lupus Erythematosus Responder Index 4 (SRI-4) at Month 6 as Compared to Baseline | Non-responder | 43 participants |
Comparison: A generalized mixed effects model for repeated measures was applied to the SRI-4 response from Month 1 through 6 with treatment group, month, treatment group by month interaction, and stratification factors (oral corticosteroids dose \& mSLEDAI-2K) as fixed effects \& participant as random effect.p-value: 0.97495% CI: [0.54, 1.9]Mixed Models Analysis
Comparison: A generalized mixed effects model for repeated measures was applied to the SRI-4 response from Month 1 through 6 with treatment group, month, treatment group by month interaction, and stratification factors (oral corticosteroids dose \& mSLEDAI-2K) as fixed effects \& participant as random effect.p-value: 0.284595% CI: [0.75, 2.65]Mixed Models Analysis
Comparison: A generalized mixed effects model for repeated measures was applied to the SRI-4 response from Month 1 through 6 with treatment group, month, treatment group by month interaction, and stratification factors (oral corticosteroids dose \& mSLEDAI-2K) as fixed effects \& participant as random effect.p-value: 0.511595% CI: [0.66, 2.32]Mixed Models Analysis
Comparison: A generalized mixed effects model for repeated measures was applied to the SRI-4 response from Month 1 through 6 with treatment group, month, treatment group by month interaction, and stratification factors (oral corticosteroids dose \& mSLEDAI-2K) as fixed effects \& participant as random effect.p-value: 0.511595% CI: [0.66, 2.32]Mixed Models Analysis