Lupus Erythematosus, Systemic, Lupus Nephritis
Conditions
Keywords
Chimeric Antigen Receptor-T (CAR-T), rapcabtagene autoleucel, Lupus Nephritis (LN), Systemic Lupus Erythematosus (SLE)
Brief summary
The purpose of this study is to evaluate the efficacy and safety of rapcabtagene autoleucel (administered once following lymphodepletion) in patients with active, refractory systemic lupus erythematosus (SLE) or active, refractory lupus nephritis (LN).
Interventions
BIOLOGICALrapcabtagene autoleucel
single infusion of rapcabtagene autoleucel
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Men and women with SLE, aged \>= 18 years and =\< 75 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 or active systemic lupus erythematosus * 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 therapies Key
Exclusion criteria
* 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. * Grade 2 or higher thromboembolic event in the past 4 weeks prior to screening. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the efficacy of rapcabtagene autoleucel | Week 24, Week 52 | Defined as: Meeting the criteria of the Definition Of Remission In Systemic Lupus Erythematosus (DORIS) or Achieving complete renal response (CRR) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of participants achieving complete renal response (CRR) | Week 52 | CRR is a composite endpoint |
| Number of weeks where Lupus Low Disease Activity Score (LLDAS) was achieved | Week 12 to Week 52 | Lupus Low Disease Activity State (LLDAS) |
| PPercentage of participants without flaring (i.e., 1 new BILAG2004 A or 2 new BILAG2004 B flares) | Week 12 to Week 52 | British Isles Lupus Activity Group (BILAG2004) records disease activity occurring over the past 4 weeks. |
| Annualized cumulative corticosteroids dose | Week 52 | The total dose of corticosteroids used up to Week 52 per patient. |
| Percentage of participants who are negative for serological status | Week 52 | The percentage of participants with negative serological status |
| FACIT-Fatigue score change from baseline | Baseline to Week 52 | Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue is a 13-item patient- reported outcomes measure |
| Maintained DORIS | Week 52 to Week 76 | Definition Of Remission In Systemic Lupus Erythematosus (DORIS) |
Countries
Argentina, Australia, Austria, Brazil, Czechia, Denmark, France, Germany, Hungary, Israel, Italy, Japan, Mexico, Netherlands, Norway, Poland, Romania, Saudi Arabia, Singapore, South Korea, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States
Contacts
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Outcome results
None listed