CABA-201 for Systemic lupus erythematosus | Lupus nephritis

Inclusion criteria

• {"criterion_text":"- Able to provide informed consent.\n- Diagnosed with active SLE. Subjects with either LN or without LN will be eligible, if they meet the following criteria: - For LN subjects: urine protein-to-creatinine ratio (UPCR) ≥1 mg/mg despite prior or current treatment with standard of care therapy\n- Adequate renal function\n- Adequate hepatic function\n- Have received all recommended vaccinations, including against COVID-19/severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), per the Centers for Disease Control and Prevention (CDC) or local/institutional guidelines for immunocompromised individuals before or during Screening. o Live vaccines must be administered at least 30 days prior to the Pre-Infusion Visit. o Non-live vaccines should be administered to subjects at least 2 weeks prior to the start of study drug infusion. If possible, non-live vaccines should also be administered at least 2 weeks prior to Leukapheresis.\n- Clinical stability by vital signs assessment at the time of screening\n- Women of reproductive potential (Section 9.4) who are sexually active must agree to use 1 highly effective method of contraception\n- Age ≥18 to ≤65 years.\n- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.\n- A clinical diagnosis of SLE, based on the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for adult SLE.\n- Positive antinuclear antibody (ANA) titer or positive anti-dsDNA antibody at Screening."}

Exclusion criteria

• {"criterion_text":"- Treatment with rituximab or other B cell-depleting agent within 26 weeks prior to Screening\n- Previous CAR T cell therapy.\n- Prior solid organ (heart, liver, kidney, lung) transplant or hematopoietic cell transplant.\n- For LN subjects only: Evidence of severe chronicity on kidney biopsy, defined as a modified National Institute of Health chronicity index score of 3+ for any of the following individual biopsy features: total glomerulosclerosis score, fibrous crescents, tubular atrophy, or interstitial fibrosis.\n- Pregnant or lactating woman, or plan to become pregnant within 52 weeks following CABA-201 infusion.\n- Men of reproductive potential (see Section 9.4) who plan to father a child in the 52 weeks following CABA-201 infusion.\n- Unable or unwilling to comply with protocol.\n- Treatment with any investigational agent within 4 weeks or 5 half-lives, whichever is longer. Note: Subjects who had received a C5 inhibitor (e.g., eculizumab, ravulizumab) may be eligible earlier than 5 half-lives after the last C5 inhibitor administration if, at Screening, they have evidence of complement lab testing (i.e., total hemolytic complement [CH50] measurement) that has normalized or returned to pre-treatment levels.\n- Diagnosis of cancer, except basal or squamous cell skin cancer or carcinoma in situ of the cervix that has been excised and cured and at least 5 years since excision.\n- Planned major surgery (including joint surgery) within 52 weeks following the CABA-201 infusion.\n- Contraindication to Leukapheresis.\n- Active infection requiring medical intervention at Screening.\n- History of anaphylactic or severe systemic reaction to FLU, CY, any of their metabolites\n- A diagnosis of antiphospholipid antibody syndrome\n- Positive human immunodeficiency virus (HIV), hepatitis C antibody, or hepatitis B surface antigen test, or evidence of active or chronic tuberculosis at Screening.\n- Autoimmune disorder other than SLE requiring immunosuppressive therapies.\n- The presence of kidney disease other than active lupus nephritis\n- Current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, pulmonary, psychiatric, cardiac, neurological, or cerebral disease, including severe and uncontrolled infections, such as sepsis and opportunistic infections.\n- Concomitant medical conditions that, in the opinion of the investigator, might place the subject at unacceptable risk for participation in this study, interfere with the assessment of the effects or safety of the investigational product or with the study procedures.\n- The presence of severe edema or anasarca at Screening\n- Moderate-to-severe chronic pulmonary disease\n- Impaired cardiac function or clinically significant cardiac disease, including: a. Unstable angina or myocardial infarction or coronary artery bypass graft within 26 weeks prior to Leukapheresis. b. New York Heart Association stage III or IV congestive heart failure. c. History of clinically significant cardiac arrhythmia (e.g., ventricular tachycardia), complete left bundle branch block, high-grade atrioventricular block d. History of severe non-ischemic cardiomyopathy. e. Left ventricular ejection fraction <45% as assessed by echocardiogram or multi-gated acquisition scan (if performed) ≤8 weeks of Leukapheresis. f. Active, severe cardiac manifestations of SLE, including constrictive pericarditis, hemodynamically significant pericardial effusions, and myocarditis at the time of screening."}

Primary endpoints

• {"endpoint_text":"- AEs occurring within 28 days after CABA-201 infusion, including DLTs and AEs related to CABA-201.","definition_or_measurement_approach":"Assessment and recording of adverse events (AEs) and dose-limiting toxicities (DLTs) occurring within 28 days after CABA-201 infusion as per protocol safety assessments."}

Secondary endpoints

• {"endpoint_text":"- AEs, vital signs, physical examination, and clinical laboratory tests occurring within 156 weeks after CABA-201 infusion.","definition_or_measurement_approach":"Safety assessments over 156 weeks including monitoring of adverse events, vital signs, physical examinations, and clinical laboratory tests."}
• {"endpoint_text":"- Changes from baselinea in WBC with differential, including B cell counts.","definition_or_measurement_approach":"Laboratory measurement of white blood cell count with differential and B cell counts versus baseline values."}
• {"endpoint_text":"- Frequency of reaching released product at target dose.","definition_or_measurement_approach":"Assessment of manufacturing outcome: count/frequency of released product batches achieving the target dose per manufacturing run."}
• {"endpoint_text":"- Fold cell expansion, transduction efficiency, vector copy number per cell, and product phenotype; Total number of CABA-201-positive cells in each manufacturing run; Percent of CAR-transduced cells in the total number of cells for infusion.","definition_or_measurement_approach":"Manufacturing and cellular product characterization metrics measured for each manufacturing run (cell expansion fold, transduction efficiency, vector copy number, phenotype, total CABA-201-positive cells, percent CAR-transduced cells)."}
• {"endpoint_text":"- Number and percentage of CABA-201-positive cells in the peripheral blood of subjects over time.","definition_or_measurement_approach":"Peripheral blood monitoring of CABA-201-positive cells (absolute number and percentage) at scheduled timepoints post-infusion."}
• {"endpoint_text":"- Changes from baseline in anti-dsDNA antibodies, C3, C4, and CH50.","definition_or_measurement_approach":"Serologic measurements of anti-dsDNA, complement components C3, C4 and CH50 versus baseline."}
• {"endpoint_text":"- Changes in UPCR, eGFR, SLEDAI-2K score, BILAG-2004 score, PGA score, joint counts, CLASI score, and SDI.; Proportions of subjects achieving complete renal response (for LN cohort only), SRI-4, BICLA responses, and LLDAS and DORIS criteria.","definition_or_measurement_approach":"Clinical and laboratory assessments for disease activity and organ-specific measures; calculation of response rates (complete renal response for LN cohort, SRI-4, BICLA, LLDAS, DORIS) per protocol-defined criteria."}
• {"endpoint_text":"- Time to achieve complete renal response (for LN cohort only), SRI-4, SRI-5, SRI-6, BICLA responses, LLDAS, and DORIS remission.","definition_or_measurement_approach":"Time-to-event analysis measuring days/weeks from infusion to achieving specified response/remission endpoints per protocol definitions."}
• {"endpoint_text":"- Change from baseline in the dose of concomitant corticosteroids and other SLE-related therapies.; Proportion of subjects achieving a dose of ≤5 mg/day oral prednisone or equivalent.; Proportion of subjects who require no SLE-related therapies.","definition_or_measurement_approach":"Assessment of concomitant medication dosing over time versus baseline; calculation of proportions achieving specified corticosteroid dose thresholds or drug-free status."}
• {"endpoint_text":"- Changes from baselinea in SF-36v2, pain NRS, FACIT-F, PtGA, Lupus QoL, and EQ-5D-5L scores.","definition_or_measurement_approach":"Patient-reported outcome instruments administered per schedule; changes from baseline in standardized scores."}
• {"endpoint_text":"- Incidences of mild/moderate and severe disease flare per BILAG-2004 and SFI.; Time to mild/moderate and severe disease flare.","definition_or_measurement_approach":"Assessment of disease flares classified by BILAG-2004 and SFI criteria; incidence counts and time-to-flare analyses."}
• {"endpoint_text":"- Proportions of subjects achieving drug free complete renal response (for LN cohort only), SRI-4, BICLA responses, LLDAS, and DORIS remissions.","definition_or_measurement_approach":"Proportion calculations of subjects meeting specified composite clinical endpoints without concomitant SLE medications where indicated."}
• {"endpoint_text":"- Time to achievement of drug-free complete renal response (for LN cohort only), SRI-4, BICLA responses, LLDAS and DORIS remission.","definition_or_measurement_approach":"Time-to-event analyses for achieving drug-free response/remission endpoints as defined in the protocol."}

Methods

• Recruitment and Informed Consent Procedure Template (documents available; versions in French and Spanish) — outlines recruitment arrangements and consent process.
• RealTime-Pay Patient Portal (screenshots provided) — patient portal materials for payments/reimbursements to participants.
• Welcome Letter and Contact Card-Magnet — participant-facing materials used in engagement/recruitment.
• Travel Request Form, Travel and Reimbursement FAQ, Patient and Caregiver Meals and Incidentals Report — logistical support for participants (travel reimbursement/assistance) to facilitate participation.
• Addendum to consent / Patient Transportation documents — describes transport support arrangements for participants.

Spain

Earliest CTIS Part Ii Submission Date

20-08-2024

Latest Decision Or Authorization Date

01-12-2025

Processing Time Days

468

Number Of Sites

2

Number Of Participants

2

France

Earliest CTIS Part Ii Submission Date

08-10-2024

Latest Decision Or Authorization Date

26-01-2026

Processing Time Days

475

Number Of Sites

3

Number Of Participants

4

Primary sponsor

Full Name

Cabaletta Bio Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Third parties

• {"country":"United States","full_name":"Elligo Health Research Inc.","duties_or_roles":"Travel Service","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Advanced Therapies LLC","duties_or_roles":"CABA-201 Manufacturer","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Cellcarta Fremont LLC","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Cell&Co","duties_or_roles":"EU import and QP site","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"CellCarta (Antwerp)","duties_or_roles":"code: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Canfield Scientific Inc.","duties_or_roles":"Image Analyses","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Cryoport Inc.","duties_or_roles":"Logistics","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Pharma Start LLC","duties_or_roles":"Home Health Provider","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Cellcarta Naperville LLC","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Merative US LP","duties_or_roles":"Electronic Data Capture","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Bioreliance Corp.","duties_or_roles":"CABA-201 Manufacturer","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Advent Bioservices Limited","duties_or_roles":"Importation of apheresis material from EU; Cryopreservation of apheresis material for EU and UK clinical sites; Site of QP batch certification for UK (in conjunction with Cell&Co); Distribution of drug product to UK clinical sites","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Advanced Clinical GmbH","duties_or_roles":"sponsorDuties codes: 1, 12, 5, 8","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}