A Study of Rapcabtagene Autoleucel in Systemic Lupus Erythematosus (SLE) Patients With Active, Refractory Lupus Nephritis (LN)
- Conditions
- Lupus Erythematosus, SystemicLupus Nephritis
- Interventions
- Biological: rapcabtagene autoleucel Regimen 2Biological: rapcabtagene autoleucel Regimen 1Other: Standard of Care
- Registration Number
- NCT06581198
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief 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).
- Detailed Description
This is a Phase 2, adaptive, two-year, randomized, assessor-blinded, active controlled study:
* Part A: Participants suffering from systemic lupus erythematosus (SLE) with active, refractory LN will be randomized to Regimen 1, Regimen 2, or SOC.
* Part B: Participants suffering from SLE with active, refractory LN will be randomized to the selected regimen from Part A or SOC.
The study will consist of two periods:
* A screening period lasting up to 6 weeks, and
* A randomized treatment period and primary follow-up period lasting up to 104 weeks.
After end of study (EOS), participants who received rapcabtagene autoleucel infusion will enter a long-term follow-up (LTFU) period lasting up to 15 years after rapcabtagene autoleucel infusion. This LTFU will be described in a separate study protocol.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 144
- Men and women with SLE, aged >= 18 years and =< 65 years at screening, fulfilling the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for SLE at screening.
- Participant must be positive for at least one of the following autoantibodies at screening: antinuclear antibodies (ANA) at a titer of >= 1:80 (on HEp-2 cells or an equivalent positive test), or anti-dsDNA (above the ULN); or anti-Sm (above the ULN) as determined by a central laboratory.
- Active lupus nephritis without signs of significant chronicity
- SLEDAI-2K Criteria at screening: SLEDAI-2K score >= 6 points (Gladman et al 2002, Touma et al 2011), excluding points attributed to "fever", "lupus headache", "alopecia", and "organic brain syndrome".
- Inadequate response at screening to at least two LN treatment regimens
Key
- Any acute, severe lupus related-flare at screening that needs immediate treatment other than pulse GCs and/or makes the immunosuppressive washout impossible and, thus, makes the participant ineligible for CD19 CAR-T therapy
- Inadequate organ function during screening and prior to randomization
- History or current diagnosis of ECG or cardiac abnormalities indicating significant risk of safety for participants prior to randomization
- Human immunodeficiency virus (HIV) positivity at screening.
- Acute or chronic infection with hepatitis B (HBV) or hepatitis C (HCV) at screening.
- Evidence of active or latent tuberculosis.
- Grade 2 or higher thromboembolic event in the past 4 weeks prior to screening.
- Vaccination (including with live attenuated vaccines) not completed at least 6 weeks prior to randomization.
Other protocol-defined inclusion/exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Regimen 2 rapcabtagene autoleucel Regimen 2 rapcabtagene autoleucel Regimen 2 Regimen 1 rapcabtagene autoleucel Regimen 1 rapcabtagene autoleucel Regimen 1 Standard of Care Standard of Care The treatment regimen must be in line with Kidney Disease Improving Global Outcomes (KDIGO) guidelines for treatment of class III/IV LN.
- Primary Outcome Measures
Name Time Method Part A and Part B: Percentage of participants achieving clinical response at Week 52. 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.
- Secondary Outcome Measures
Name Time Method Part A and Part B: Percentage of participants achieving complete renal response (CRR) at Week 52 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
Part A and Part B: Number of weeks where Lupus Low Disease Activity Score (LLDAS) was achieved from Week 12 until Week 52 Week 12 to 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.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 Week 12 to 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.
Part A and Part B: Annualized cumulative corticosteroids dose until Week 52 Week 52 The total dose of corticosteroids used up to Week 52 per patient.
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 Week 52 The percentage of participants who are negative for antinuclear antibodies anti-dsDNA \& anti-Sm will be analyzed like the Clinical Response.
Part A and Part B: FACIT-Fatigue score change from baseline at Week 52 Baseline to 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.
Part A and Part B: Percentage of participants who were in Sustained Remission at Week 52 to Week 76 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.
Trial Locations
- Locations (8)
UCSF
🇺🇸San Francisco, California, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
University Of Iowa
🇺🇸Iowa City, Iowa, United States
University of Kentucky
🇺🇸Lexington, Kentucky, United States
Boston Medical Center
🇺🇸Boston, Massachusetts, United States
Oregon Health Sciences University
🇺🇸Portland, Oregon, United States
Univ Of TX MD Anderson CC
🇺🇸Houston, Texas, United States
Novartis Investigative Site
🇪🇸Madrid, Spain