An Exploratory Clinical Study of Anti-CD19 CAR NK Cells in the Treatment of Systemic Lupus Erythematosus

An Exploratory Clinical Study of the Safety and Efficacy of Anti-CD19 Chimeric Antigen Receptor (CAR) Nature Killer Cells (KN5501) in the Treatment of Moderate to Severe Refractory Systemic Lupus Erythematosus (SLE)

A single arm, open-label pilot study is designed to determine the safety and effectiveness of anti-cluster of differentiation antigen 19 (CD19) chimeric antigen receptor (CAR) natural killer (NK) cells (KN5501) in patients with moderate to severe refractory systemic lupus erythematosus (SLE). 36 patients are planned to be enrolled in the dose-escalation trial. The primary objective of the study was to evaluate the safety of allogeneic anti-CD19 CAR-NK cells (KN5501) for the treatment of patients with moderate to severe refractory active SLE. The secondary objective is to evaluate the efficacy of anti-CD19 CAR NK cells (KN5501) in patients with moderate to severe refractory SLE, including British Isles Lupus Assessment Group 2004 (BILAG-2004) index, Systemic Lupus Erythematosus Responder Index (SRI)-4 response rate, Lupus Low Disease Activity State (LLDAS) rate, and Definitions Of Remission In SLE (DORIS) remission rate.

Study Overview

• Status: Recruiting
• Conditions: Systemic Lupus Erythematosus (SLE)
• Intervention / Treatment: Drug: anti-CD19 CAR NK cells (KN5501)

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Dongbao Zhao, Doctor; Phone Number: +86-15921061314; Email: dongbaozhao@163.com

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Changhai Hospital
    • Contact: Dongbao Dongbao Zhao, Doctor; Phone Number: +86-15921061314; Email: dongbaozhao@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age: ≥ 18 years old and ≤ 65 years old, male or female, subjects voluntarily participate in this clinical study and sign the Informed Consent Form (ICF)
2. Previous diagnosis of systemic lupus erythematosus (SLE) (according to the 1997 American Rheumatology Association criteria)
3. Females of childbearing potential must use effective contraception during study treatment and for 90 days after the last dose of study treatment. In addition, subjects must not donate eggs during the study and for at least 90 days after the last dose of study treatment
4. Subjects with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K) score ≥ 8 points prior to screening
5. Subject has ≥ 1 organ system with BILAG-2004 Class A mobility score or ≥ 2 organ systems with BILAG-2004 Class B mobility score prior to screening

6. Subjects meets one of the following:

   1. Antinuclear antibody (ANA) ≥ 1:80, determined by immunofluorescence method;
   2. Anti-dsDNA antibodies are higher than normal level;
   3. Anti-Smith antibodies are higher than normal level
7. Absolute number of neutrophils ≥ 1.0×10^9/L, hemoglobin ≥ 60g/L
8. Left ventricular ejection fraction (LVEF) ≥ 50%
9. Subjects have been treated with oral corticosteroids (OCS) in combination with an immunosuppressive or biologic agent for at least 6 months prior to enrollment

Exclusion Criteria:

1. Subjects with known severe allergic reactions, hypersensitivity, contraindication to any medications during the trial (cyclophosphamide, fludarabine, obinutuzumab), or subjects with a history of severe allergic reactions
2. Subjects with active infection receiving intravenous (IV) antibiotic treatment, or received intravenous (IV) antibiotic treatment within one week prior to anti-CD19 CAR NK Cells infusion
3. Subjects with acquired and congenital immunodeficiency diseases
4. Subjects with grade III or IV heart failure (NYHA classification)
5. History of epilepsy or other central nervous system (CNS) diseases
6. History of severe herpetic infection, such as herpetic encephalitis, ocular herpes, or diffuse herpes

7. History of other primary malignant tumors except:

   1. Cured non-melanoma skin cancer by surgical excision, for example basal cell carcinoma (BCC) ;
   2. Cured primary malignant tumors, such as cervical cancer, superficial bladder cancer, breast cancer
8. Signs of herpes or varicella-zoster virus infection (especially chickenpox, shingles) within 12 weeks prior to screening; History of any cardiac, endocrine, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, and renal disease or other major medical condition that would prevent the administration of anti-CD19 CAR NK Cells (KN5501), except for lupus (determined by the investigator)
9. Females who are pregnant, lactating, or planning a pregnancy within six months
10. Any active skin disease that may interfere with the study assessment of SLE, including but not limited to psoriasis, dermatomyositis, systemic sclerosis, non-LE cutaneous lupus manifestations (eg, cutaneous vascular disease, periungual telangiectasia, fingertip sclerosis, rheumatoid nodules, erythema multiforme, leg ulcers) or drug-induced lupus
11. Subjects who have received other clinical trial treatment within 3 months
12. Subjects who have received B cell-targeted drug therapy within 1 month before enrollment
13. Any abnormal laboratory test results judged by the investigator to be clinically significant and prevent the subject from participating in the study. Laboratory test values that are out of range and not of clinical significance will not be considered as exclusion criteria
14. Any situation judged by the investigators that may increase the risk of the subjects or interfere with the clinical trial outcome

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: anti-CD19 CAR NK cells; To evaluate the safety and effectiveness of anti-CD19 CAR NK cells (KN5501) in patients with moderate to severe refractory SLE. All subjects will receive fludarabine/cyclophosphamide lymphodepletion followed by anti-CD19 CAR NK cells infusion.	Drug: anti-CD19 CAR NK cells (KN5501); Patients will receive Fludarabine (25 mg/m2 per day) and Cyclophosphamide (300mg/m2 per day) on day -5, -4, and -3. Multiple doses of anti-CD19 CAR NK cells (KN5501) will infused in each group using the "3 + 3" dose-escalation strategy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Dose Limiting Toxicity (DLTs)	To characterize the safety of anti-CD19 CAR NK Cells for moderate to severe refractory SLE	within 4 weeks after infusion; 12, 24, 36 and 52 weeks after infusion
Incidence of Treatment Emergent Adverse Events (TEAEs)	To characterize the safety of anti-CD19 CAR NK Cells for moderate to severe refractory SLE	within 4 weeks after infusion; 12, 24, 36 and 52 weeks after infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SRI-4 response rate of subjects	To characterize the efficacy of anti-CD19 CAR NK Cells for moderate to severe refractory SLE	12, 24,36, and 52 weeks after infusion
LLDAS rate of subjects	To characterize the efficacy of anti-CD19 CAR NK Cells for moderate to severe refractory SLE	12, 24,36, and 52 weeks after infusion
DORIS remission rate of subjects	To characterize the efficacy of anti-CD19 CAR NK Cells for moderate to severe refractory SLE	12, 24,36, and 52 weeks after infusion

Collaborators and Investigators

• Sponsor: Changhai Hospital
• Collaborators: Rui Therapeutics Co., Ltd
• Investigators: Principal Investigator: Dongbao Zhao, Doctor, ChanghaiHospital

Study record dates

Study Major Dates

• Study Start (Actual): August 20, 2023
• Primary Completion (Estimated): August 25, 2026
• Study Completion (Estimated): August 25, 2027

Study Registration Dates

• First Submitted: August 7, 2023
• First Submitted That Met QC Criteria: August 23, 2023
• First Posted (Actual): August 24, 2023

Study Record Updates

• Last Update Posted (Actual): April 29, 2025
• Last Update Submitted That Met QC Criteria: April 26, 2025
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Autoimmune disorders; Connective Tissue Diseases; Lupus Erythematosus, Systemic
• Additional Relevant MeSH Terms: Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: CHEC2023-174

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No