Examining Distinct Immunophenotypes to Validate and Enhance Rational Treatment in Systemic Lupus
- Conditions
- Systemic Lupus Erythematosus
- Interventions
- Drug: Placebo for Voclosporin
- Registration Number
- NCT05306873
- Brief Summary
The primary purpose of this study is to evaluate the potential effectiveness of 24 weeks of MMF within previously discovered immunologically defined subsets of SLE patients. Treatment effects will be evaluated within the individual immunologically-homogenous subsets defined at screening. This study will also explore and compare pre-randomization gene expression patterns among responders and non-responders to MMF and MMF plus voclosporin, use comprehensive immunophenotyping to study the immunologic changes that accompany treatment- induced disease improvement and to better understand immunologic changes associated with the loss of clinical response.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 120
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description MMF Mycophenolate Mofetil Participants will receive 500 mg mycophenolate mofetil (MMF) bid for 7 days, followed by 500mg and 1,000mg MMF in divided doses for 7 days. They will then continue at a stable dose of 1,000mg MMF bid. Visits to evaluate AEs, vital signs, hematology and chemistry, study medication compliance, medication use, disease status, participant reported outcomes, and to obtain biomarker samples will occur every 4 weeks after randomization Placebo for MMF Placebo for Mycophenolate Mofetil Participants will receive 500 mg corresponding mycophenolate mofetil (MMF) placebo bid for 7 days, followed by 500mg and 1,000mg corresponding MMF placebo in divided doses for 7 days. They will then continue at a stable dose of 1,000mg corresponding MMF placebo bid. Visits to evaluate AEs, vital signs, hematology and chemistry, study medication compliance, medication use, disease status, participant reported outcomes, and to obtain biomarker samples will occur every 4 weeks after randomization MMF+ Placebo for Voclosporin Mycophenolate Mofetil Participants randomized in this arm will receive up to 24 weeks of mycophenolate mofetil (MMF) plus placebo for voclosporin, also during the first 2 weeks of treatment, a single intramuscular injection of a long-acting corticosteroid may be administered if needed to achieve amelioration of symptoms without meeting the definition of treatment failure in Stage 3 and without a requirement to stop Stage 3 study-provided medication MMF+ Placebo for Voclosporin Placebo for Voclosporin Participants randomized in this arm will receive up to 24 weeks of mycophenolate mofetil (MMF) plus placebo for voclosporin, also during the first 2 weeks of treatment, a single intramuscular injection of a long-acting corticosteroid may be administered if needed to achieve amelioration of symptoms without meeting the definition of treatment failure in Stage 3 and without a requirement to stop Stage 3 study-provided medication MMF+ Voclosporin Voclosporin Participants randomized in this arm will receive up to 24 weeks of mycophenolate mofetil (MMF) plus voclosporin, also during the first 2 weeks of treatment, a single intramuscular injection of a long-acting corticosteroid may be administered if needed to achieve amelioration of symptoms without meeting the definition of treatment failure in Stage 3 and without a requirement to stop Stage 3 study-provided medication MMF+ Voclosporin Mycophenolate Mofetil Participants randomized in this arm will receive up to 24 weeks of mycophenolate mofetil (MMF) plus voclosporin, also during the first 2 weeks of treatment, a single intramuscular injection of a long-acting corticosteroid may be administered if needed to achieve amelioration of symptoms without meeting the definition of treatment failure in Stage 3 and without a requirement to stop Stage 3 study-provided medication
- Primary Outcome Measures
Name Time Method The cumulative incidence of participants who experience a Stage 2 treatment failure at or before the Stage 2 Week 24 visit. At or before the Stage 2 Week 24 visit Treatment failure is defined as the first occurrence after randomization (Stage 2) of any of the following events:
1. Corticosteroid injections or treatment with a new or increased lupus medication, except the occasional use of corticosteroids for reasons not associated with Systemic Lupus Erythematosus (SLE) flare or
2. British Isles Lupus Assessment Group (BILAG) flare, defined as any item marked new or worse that could support a BILAG A (severe flare) or 2 organs with items marked new or worse that could support a BILAG B (moderate flare), and if the participant's condition is deemed by the investigator to be "moderately worse" or "much worse" compared to the day of randomization, as assessed by the Clinician Global Impression of Change (CGI-C); or
3. Premature permanent discontinuation of study-assigned treatment for any reason
- Secondary Outcome Measures
Name Time Method The incidence of Grade 3 or higher hypertension in stage 3 After Stage 3 re-randomization Day 0 to Stage 3 Week 24 Defined as a systolic blood pressure \>= 160 mm Hg or a diastolic blood pressure of \>= 100 mm Hg
The incidence of Grade 3 or higher infections in Stage 3 After Stage 3 re-randomization Day 0 to Stage 3 Week 24 The incidence of renal dysfunction in Stage 1 Day -28 to Day -1 Defined as Grade 3 or higher chronic kidney disease with eGFR \< 30 ml/min per 1.73 m\^2
The incidence of renal dysfunction in Stage 2 Stage 2 Day 0 up to Stage 2 Week 48 Defined as Grade 3 or higher chronic kidney disease with eGFR \< 30 ml/min per 1.73 m\^2
The incidence of renal dysfunction in Stage 3 After Stage 3 re-randomization Day 0 to Stage 3 Week 24 Defined as Grade 3 or higher chronic kidney disease with eGFR \< 30 ml/min per 1.73 m\^2
The incidence of Grade 3 or higher hypertension in Stage 1 Day -28 to Day -1 The incidence of Grade 3 or higher hypertension, defined as a systolic blood pressure \>=160 mm Hg or a diastolic blood pressure of \>= 100 mm Hg
The incidence of Grade 3 or higher hypertension in stage 2 Stage 2 Day 0 up to Stage 2 Week 48 The incidence of Grade 3 or higher hypertension, defined as a systolic blood pressure \>=160 mm Hg or a diastolic blood pressure of \>= 100 mm Hg
Clinical response in Stage 2 defined by the BILAG-based Combined Lupus Assessment (BICLA) at Stage 2 Week 24 At Stage 2 Week 24 Clinical response at Week 24 is defined by the BICLA as follows:
* All BILAG A scores must improve to B, C, or D, and
* All BILAG B scores must improve to C or D, and
* No new BILAG A scores among organs scored as B, C, D, or E, and
* ≤ 1 new BILAG B scores among organs scored as C, D, or E , and
* No worsening of H-SLEDAI total score, and
* Less than a 10% increase (worsening) in the Physician's Global Assessment (visual analogue scale).
The reference values for BILAG, H-SLEDAI total score and PGA are the assessments obtained at the Screening Visit.The cumulative incidence of participants who experience a Stage 3 treatment failure after re-randomization (Stage 3) and on or before completing Stage 3. At or before the Stage 3 Week 24 visit Treatment failure is defined as the first occurrence of any of the following events:
1. Corticosteroid injections or treatment with a new or increased lupus medication, except the occasional use of corticosteroids for reasons not associated with SLE flare (see Section 7.1.2.2, Prednisone (or equivalent) for additional information); or
2. BILAG flare, defined as any item marked new or worse that could support a BILAG A (severe flare) or 2 organs with items marked new or worse that could support a BILAG B (moderate flare), and if the participant's condition is deemed by the investigator to be "moderately worse" or "much worse" compared to the day of randomization, as assessed by the Clinician Global Impression of Change (CGI-C); or
3. Premature permanent discontinuation of study-assigned treatment for any reason.Time to treatment failure in Stage 3 From the day of Stage 3 randomization until the date of Stage 3 clinical response, assessed up to the Week 24 visit defined as the interval from the day of Stage 3 randomization until the day of treatment failure.
Clinical response in Stage 3 At Stage 3 Week 24 Defined by the Based Combined Lupus Assessment (BICLA) at Stage 3 Week 24.
The incidence of Grade 3 or higher related Adverse Events (AEs) in Stage 2 Stage 2 Day 0 up to Stage 2 Week 48 Adverse Events (AEs) will be evaluated separately for each stage of the study
The incidence of Grade 3 or higher related Adverse Events (AEs) in Stage 3 After Stage 3 re-randomization Day 0 to Stage 3 Week 24 Adverse Events (AEs) will be evaluated separately for each stage of the study
The incidence of Grade 3 or higher infections in Stage 1 Day -28 to Day -1 The incidence of Grade 3 or higher infections in Stage 2 Stage 2 Day 0 up to Stage 2 Week 48
Trial Locations
- Locations (10)
UCLA Medical Center: Division of Rheumatology
🇺🇸Los Angeles, California, United States
Yale University School of Medicine: Rheumatology, Allergy & Immunology
🇺🇸New Haven, Connecticut, United States
Emory University School of Medicine: Division of Rheumatology
🇺🇸Atlanta, Georgia, United States
Piedmont Healthcare: Rheumatology Atlanta
🇺🇸Atlanta, Georgia, United States
Massachusetts General Hospital: Rheumatology, Allergy and Immunology, Center for Immunology and Inflammatory Diseases
🇺🇸Boston, Massachusetts, United States
Feinstein Institute for Medical Research: Center for Autoimmune and Musculoskeletal Diseases
🇺🇸Manhasset, New York, United States
Columbia University Medical Center: Department of Medicine, Division of Rheumatology
🇺🇸New York, New York, United States
University of North Carolina at Chapel Hill; Thurston Arthritis Research Center: Division of Rheumatology, Allergy, and Immunology
🇺🇸Chapel Hill, North Carolina, United States
Oklahoma Medical Research Foundation: Arthritis and Clinical Immunology Research Program
🇺🇸Oklahoma City, Oklahoma, United States
PennState Health Milton S. Hershey Medical Center: Division of Rheumatology
🇺🇸Hershey, Pennsylvania, United States