A Study of Rapcabtagene Autoleucel in Systemic Lupus Erythematosus (SLE) Patients With Active, Refractory Lupus Nephritis (LN)
NCT Number: NCT06581198
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Lupus Erythematosus, Systemic|Lupus Nephritis
Interventions: BIOLOGICAL: rapcabtagene autoleucel Regimen 1|BIOLOGICAL: rapcabtagene autoleucel Regimen 2|OTHER: Standard of Care
Sponsor: Novartis Pharmaceuticals
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 144
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: SINGLE (OUTCOMES_ASSESSOR)|Primary Purpose: TREATMENT
Start Date: 2024-08-30
Completion Date: 2030-06-04
Locations: Northwestern University Research, Chicago, Illinois, 60611, United States|University Of Iowa, Iowa City, Iowa, 52242, United States|Novartis Investigative Site, Singapore, 119074, Singapore

Summary:
The purpose of this study is to evaluate the efficacy and safety of rapcabtagene autoleucel (administered once following lymphodepletion) versus Standard of Care (SOC) in patients with systemic lupus erythematosus (SLE) with active, refractory lupus nephritis (LN).

Primary Outcome Measures: Part A and Part B: Percentage of participants achieving clinical response at Week 52., Clinical response is defined as meeting the criteria of the Definition Of Remission In Systemic Lupus Erythematosus (DORIS) AND maintaining treatment with low dose glucocorticoids (GCs) from Week 24 onward as defined by:

* Clinical Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K of 0 at Week 52 AND
* Achieving a Physician Global Assessment (PhGA) score of \<0.5 at Week 52 AND
* GC treatment with low prednisone dose/day or equivalent from Week 24 onward AND
* Stable immunomodulatory/immunosuppressive treatment., Week 52
Secondary Outcome Measures: Part A and Part B: Percentage of participants achieving complete renal response (CRR) at Week 52, CRR is a composite endpoint defined as: estimated glomerular filtration rate (eGFR) ≥ 90 ml/min/1.73 m2 (eGFR within normal range) or no less than 85% of baseline AND 24-hour UPCR \< 0.5, Week 52|Part A and Part B: Number of weeks where Lupus Low Disease Activity Score (LLDAS) was achieved from Week 12 until Week 52, Lupus Low Disease Activity State (LLDAS) has been described and validated for SLE participants and is defined by:

* SLEDAI-2K score of ≤ 4, with no activity in major organ systems (renal, central nervous system (CNS), cardiopulmonary, vasculitis, fever)
* No new lupus disease activity compared with the previous assessment
* Physician global assessment (PhGA, scale 0-3) ≤ 1
* Current GC (predniso(lo)ne or equivalent) dose ≤ 7.5 mg/day
* Well tolerated standard maintenance doses of immunosuppressive drugs and approved biological agents, excluding investigational drugs
* No discontinuation of investigational product
* No use of restricted medications beyond the protocol-allowed threshold before assessment., Week 12 to Week 52|Part A and Part B: Percentage of participants without flaring (i.e., 1 new BILAG2004 A or 2 new BILAG2004 B flares) from Week 12 through Week 52, British Isles Lupus Activity Group (BILAG2004) records disease activity occurring over the past 4 weeks. The BILAG2004 index covers 97 items, and the assessment is based on the principle of the doctor's intent to treat, which requires an assessment as 0 = not present, 1 = improving, 2 = same, 3 = worse, or 4 = new over the last month., Week 12 to Week 52|Part A and Part B: Annualized cumulative corticosteroids dose until Week 52, The total dose of corticosteroids used up to Week 52 per patient., Week 52|Part A and Part B: Percentage of participants who are negative (i.e., titer within normal limits) for antinuclear antibodies (ANA), anti-dsDNA, and anti-Sm at Week 52, The percentage of participants who are negative for antinuclear antibodies anti-dsDNA \& anti-Sm will be analyzed like the Clinical Response., Week 52|Part A and Part B: FACIT-Fatigue score change from baseline at Week 52, Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue is a 13-item patient-reported outcomes measure) that assesses self-reported fatigue and its impact upon daily activities and function over the past week. For FACIT, the score ranges from 0 to 52, with lower values indicating less fatigue., Baseline to Week 52|Part A and Part B: Percentage of participants who were in Sustained Remission at Week 52 to Week 76, Sustained remission is defined as follows: Clinical SLEDAI-2K=0 from Week 52 to Week 76, Physician Global Assessment \< 0.5 (PhGA, scale 0-3) from Week 52 to Week 76, The participant must be on stable treatment from Week 52 to Week 76., Week 52 to Week 76