A Phase 1/2, Open-Label Study to Evaluate the Safety and Efficacy of Autologous CD19-specific Chimeric Antigen Receptor T cells (CABA-201) in Subjects with Active Systemic Lupus Erythematosus

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Cabaletta Bio Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

31 Mar 2025 → ongoing

Decision date (initial)

2024-10-21

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-507613-10-01

ClinicalTrials.gov

NCT06121297

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the safety and tolerability of CABA-201 in subjects with active SLE over 28 days

Secondary objectives 13

1. To evaluate the safety and tolerability of CABA-201 in subjects with active SLE over 156 weeks.
2. To evaluate the effects of CABA-201 on WBC, including B cell counts.
3. To evaluate CABA-201 manufacturing success rates.
4. To characterize manufacturing process using subject cells.
5. To evaluate CABA-201 persistence and kinetics after infusion.
6. To evaluate the effects of CABA-201 on SLE serology.
7. To evaluate the effects of CABA-201 on SLE disease activity.
8. To evaluate the time to achieve disease response after CABA-201 infusion.
9. To evaluate the effect of CABA-201 on concomitant steroid use and other SLE-related therapy.
10. To evaluate the effect of CABA-201 on PROs and health-related QOL.
11. To evaluate the effect of CABA-201 on disease flare.
12. To evaluate the effect of CABA-201 on drug-free response.
13. To evaluate the time to achieve drug-free response after CABA-201 infusion.

Conditions and MedDRA coding

Active Systemic Lupus Erythematosus;Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by autoantibody production and abnormal B cell function. SLE presents with fluctuating severity and may cause tissue damage in a variety of organs over time. Lupus nephritis (LN) is a common severe manifestation of SLE, which can lead to significant morbidity and mortality.

Study design 1 period

Regulatory references

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Able to provide informed consent.
2. Adequate hepatic function
3. 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.
4. Clinical stability by vital signs assessment at the time of screening
5. Women of reproductive potential (Section 9.4) who are sexually active must agree to use 1 highly effective method of contraception
6. Age ≥18 to ≤65 years.
7. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.
8. A clinical diagnosis of SLE, based on the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for adult SLE.
9. Positive antinuclear antibody (ANA) titer or positive anti-dsDNA antibody at Screening.
10. 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
11. Adequate renal function

Exclusion criteria 22

1. Treatment with rituximab or other B cell-depleting agent within 26 weeks prior to Screening
2. Active infection requiring medical intervention at Screening.
3. Autoimmune disorder other than SLE requiring immunosuppressive therapies.
4. The presence of kidney disease other than active lupus nephritis
5. 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.
6. 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.
7. The presence of severe edema or anasarca at Screening
8. Moderate-to-severe chronic pulmonary disease
9. 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.
10. Previous CAR T cell therapy.
11. Prior solid organ (heart, liver, kidney, lung) transplant or hematopoietic cell transplant.
12. 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.
13. Pregnant or lactating woman, or plan to become pregnant within 52 weeks following CABA-201 infusion.
14. Men of reproductive potential (see Section 9.4) who plan to father a child in the 52 weeks following CABA-201 infusion.
15. Unable or unwilling to comply with protocol.
16. 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.
17. 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.
18. Planned major surgery (including joint surgery) within 52 weeks following the CABA-201 infusion.
19. Contraindication to Leukapheresis.
20. History of anaphylactic or severe systemic reaction to FLU, CY, any of their metabolites
21. A diagnosis of antiphospholipid antibody syndrome
22. Positive human immunodeficiency virus (HIV), hepatitis C antibody, or hepatitis B surface antigen test, or evidence of active or chronic tuberculosis at Screening.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. AEs occurring within 28 days after CABA-201 infusion, including DLTs and AEs related to CABA-201.

Secondary endpoints 13

1. AEs, vital signs, physical examination, and clinical laboratory tests occurring within 156 weeks after CABA-201 infusion.
2. Changes from baselinea in WBC with differential, including B cell counts.
3. Frequency of reaching released product at target dose.
4. 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.
5. Number and percentage of CABA-201-positive cells in the peripheral blood of subjects over time.
6. Changes from baseline in anti-dsDNA antibodies, C3, C4, and CH50.
7. 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.
8. Time to achieve complete renal response (for LN cohort only), SRI-4, SRI-5, SRI-6, BICLA responses, LLDAS, and DORIS remission.
9. 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.
10. Changes from baselinea in SF-36v2, pain NRS, FACIT-F, PtGA, Lupus QoL, and EQ-5D-5L scores.
11. Incidences of mild/moderate and severe disease flare per BILAG-2004 and SFI.; Time to mild/moderate and severe disease flare.
12. Proportions of subjects achieving drug free complete renal response (for LN cohort only), SRI-4, BICLA responses, LLDAS, and DORIS remissions.
13. Time to achievement of drug-free complete renal response (for LN cohort only), SRI-4, BICLA responses, LLDAS and DORIS remission.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Cabaletta Bio Inc.

Sponsor organisation

Cabaletta Bio Inc.

Address

2929 Arch Street Suite 600

City

Philadelphia

Postcode

19104-2857

Country

United States

Scientific contact point

Organisation

Cabaletta Bio Inc.

Contact name

Cabaletta EU Regulatory

Public contact point

Organisation

Cabaletta Bio Inc.

Contact name

Cabaletta EU Regulatory

Third parties 15

Locations

2 EU/EEA countries · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 54 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications