Systemic Lupus Erythematosus
Conditions
Keywords
Lupus Nephritis, CAR-T therapy
Brief summary
The purpose of this study is to evaluate the safety and tolerability of P-CD19CD20-ALLO1 in participants with highly active, severe, refractory SLE with or without lupus nephritis (LN). This study includes a dose-escalation stage followed by an expansion stage. It will also evaluate the cellular kinetics (CK), pharmacodynamics (PD), and efficacy of P-CD19CD20-ALLO1.
Interventions
BIOLOGICALP-CD19CD20-ALLO1 Cells
P-CD19CD20-ALLO1 cells will be administered intravenously as per the schedule specified in the protocol.
DRUGCyclophosphamide
Cyclophosphamide will be administered intravenously.
DRUGFludarabine
Fludarabine will be administered intravenously.
DRUGRimiducid
Rimiducid will be used as a rescue therapy in the event of the occurrence of severe or life-threatening adverse events. It will be administered intravenously.
Sponsors
Genentech, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion criteria: 18-75 years old SLE diagnosis per 2019 EULAR/ACR classification criteria ≥ 24 weeks Autoantibody positive and low complement at screening Treatment refractory: Failed ≥ 2 treatments for at least 3 months Highly active disease: SLEDAI-2K ≥ 8 (excluding alopecia, headache, and fever; additional protocol-specified requirements to enhance specificity of findings) BILAG-2004 cat A in ≥ 1 organ system and/or cat B in ≥ 2 organ systems (excluding constitutional, musculoskeletal, and/or mucocutaneous organ systems for category B) PGA score ≥ 1.0 on a 0 to 3 VAS For patients with lupus nephritis: Biopsy-proven Class III or IV (± Class V) active LN per 2018 ISN/RPS criteria within 12 months of screening Modified NIH activity index ≥ 1/24 UPCR ≥ 1g/g Key
Exclusion criteria
Participants who are pregnant, breastfeeding, or intend to become pregnant within the timeframe in which contraception is required Prior treatment with CAR T-cell therapy, B-cell-targeting T-cell-dependent bispecific antibody, gene therapy product, total body irradiation, allograft organ transplant, or hematopoietic stem cell transplant Significant organ impairment (renal, hepatic, cardiac, or pulmonary) or uncontrolled medical disease which, in the investigator's opinion would preclude patient participation or that may require treatment with systemic corticosteroids or immunosuppressants during the study Active severe or unstable neuropsychiatric disease Protocol-specified active or chronic infections, recent major episode of infection High-risk medical conditions (e.g. high bleeding risk, history of cancer, recent major surgery, history of HLH/MAS, substance abuse within the previous year) Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With Dose-limiting Toxicities (DLTs) at Each Dose Level of P-CD19CD20-ALLO1 | Day 1 up to Day 29 |
| Number of Participants With Adverse Events (AEs) | Up to 5 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Chimeric Antigen Receptor (CAR) Transgene Copies in Blood Assessed by Droplet Digital Polymerase Chain Reaction (ddPCR) | Up to 5 years | — |
| B-cell Levels in the Blood | Up to 5 years | — |
| Percentage of Participants who Achieve Sustained Drug-free Definition of Remission in SLE (DORIS) | From Week 24 through Week 52 | Drug-free DORIS is defined as a SLEDAI-2K = 0 and a PGA \<0.5 (on a 3-point PGA-visual analog scale \[VAS\]), without corticosteroids or other immunosuppressants. |
| Number of Participants With Anti-CAR T Antibodies | Up to 5 years | — |
Countries
United States
Contacts
STUDY_DIRECTORClinical Trials
Genentech, Inc.
Outcome results
None listed