Universal CAR-T Cell Therapy for Refractory Lupus Nephritis

A Clinical Study of the Safety and Efficacy of Universal CAR-T Cells Targeting BCMA and CD19 for the Treatment of Refractory Lupus Nephritis

This investigator-initiated trial aims to assess the efficacy and safety of combination therapy using universal CAR-T cells targeting BCMA and CD19 in refractory lupus nephritis.

Study Overview

• Status: Not yet recruiting
• Conditions: Lupus Nephritis
• Intervention / Treatment: Biological: BCMA CART + CD19 CART

Detailed Description

This study is a non-randomized, open-label, single-arm clinical trial designed to assess the efficacy and safety of combination therapy for refractory lupus nephritis using universal CAR-T cells targeting BCMA and CD19.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Dandan Wang, PhD; Phone Number: 15850515316; Email: dangdangwang2007@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aged 18-65 years; both genders eligible.
• Subjects diagnosed with lupus nephritis.
• Previous treatment outcomes were unsatisfactory.
• Diagnosis of active nephritis type III or IV with or without type V according to 2018 International Society of Nephrology and Society of Renal Pathology (ISN/RPS) criteria.
• NIH Activity Index > 2 and elevated chronicity index.
• Urine protein: creatinine ratio (UPCR) ≥ 1.0 g/g, or 24-hour urine protein ≥ 1.0 g, with or without active urine sediment with red blood cell casts.
• Receiving hormones with or without antimalarials.
• SLEDAI-2K score ≥ 6.
• Antinuclear antibody positive, and/or anti-ds-DNA antibody positive, and/or anti-Smith antibody positive.
• Positive expression of CD19 on B cells in peripheral blood.
• Agrees to use double barrier methods, condoms, oral or injectable contraceptives, or intrauterine devices during the study period and for one year after taking the study medication.
• Provides written informed consent.

Exclusion Criteria:

• History of solid organ transplantation.
• Malignant tumor within the last two years.
• Positive for Hepatitis B surface antigen (HBsAg) or Hepatitis B core antibody (HBcAb), with peripheral blood Hepatitis B virus (HBV) DNA detected as positive; positive for Hepatitis C virus antibodies, with peripheral blood Hepatitis C virus RNA detected as positive; positive for Human Immunodeficiency Virus (HIV) antibodies; positive for Cytomegalovirus (CMV) DNA; positive for syphilis.
• Primary immunodeficiency (congenital or acquired).
• Severe cardiac disease.
• History of psychiatric disorders or history of psychotropic drug abuse, with no history of withdrawal.
• Allergic constitution or a history of severe allergies.
• Pregnant or breastfeeding women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BCMA CART + CD19 CART	Biological: BCMA CART + CD19 CART; BCMA CART + CD19 CART

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AEs	The total number, incidence, and severity of AE	Within 6 months after BCMA CART and CD19 CART infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR (CR and PR)	Complete response (CR) was defined as serum creatinine ≤ 1.2 mg/dl or ≤ 125% of baseline value, and urine protein/creatinine ratio < 0.5 or 24-hour urine protein quantification < 0.5 g, and prednisone dose reduction to ≤ 10 mg/d (or equivalent dose). Partial response (PR) was defined as if both serum creatinine and urine protein/creatinine ratio (or 24-hour urine protein quantification) were abnormal before treatment, both items improved by > 30% after treatment, without other indicators of deterioration; if only urine protein/creatinine ratio (or 24-hour urine protein quantification) was abnormal before treatment, the improvement was > 50% after treatment.	At 6 months after BCMA CART and CD19 CART infusion

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK/PD	Changes and duration of CAR gene copy number and CAR-T cell number in peripheral blood after BCMA CART and CD19 CART infusion	Within 3 months after BCMA CART and CD19 CART infusion

Collaborators and Investigators

• Sponsor: Bioray Laboratories
• Collaborators: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Study record dates

Study Major Dates

• Study Start (Estimated): November 25, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: November 4, 2024
• First Submitted That Met QC Criteria: November 7, 2024
• First Posted (Estimated): November 8, 2024

Study Record Updates

• Last Update Posted (Estimated): November 8, 2024
• Last Update Submitted That Met QC Criteria: November 7, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Glomerulonephritis; Lupus Erythematosus, Systemic; Nephritis; Lupus Nephritis
• Other Study ID Numbers: 2024-BRL-302-03

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No