A Clinical Study of CD19 CAR NK Cells for the Treatment of Relapsed/Refractory B-cell Related Autoimmune Diseases

An Exploratory Clinical Study of the Safety and Efficacy of CD19 Chimeric Antigen Receptor NK Cell Injections for the Treatment of Relapsed/Refractory B-cell Related Autoimmune Diseases

A single arm, open-label pilot study is designed to determine the safety and effectiveness of anti-CD19 CAR NK cells (KN5501) in patients with relapsed/refractory B-cell related autoimmune diseases.15 patients are planned to be enrolled in the dose-escalation trial (6×10^9 cells, 9×10^9 cells). The primary objective of the study is to evaluation of the safety and feasibility of KN5501 for the treatment of relapsed/refractory B-cell related autoimmune diseases. The secondary objective is to evaluate the effectiveness of KN5501 for the treatment of relapsed/refractory B-cell related autoimmune diseases. The exploratory objective is to evaluate expansion, persistence and ability to deplete CD19 positive B cells of KN5501 in patients with relapsed/refractory B-cell related autoimmune diseases.

Study Overview

• Status: Recruiting
• Conditions: Autoimmune Diseases
• Intervention / Treatment: Drug: anti-CD19 CAR NK cells

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Zhenjiang, Jiangsu, China, 212001
      • Recruiting
      • Affiliated Hospital of Jiangsu University
      • Contact: Yu Tang; Phone Number: 086-13815153350; Email: tangtang@ujs.edu
      • Principal Investigator: Yu Tang, Dr.
    • Zhenjiang, Jiangsu, China, 212001
      • Recruiting
      • Jiangsu University Affiliated Hospital
      • Contact: Yanru Wang; Phone Number: 0511-85026079; Email: tangtang@ujs.edu
      • Principal Investigator: Yu Tang, Doctor

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Subjects voluntarily participate in this clinical study and sign the Informed Consent Form (ICF) and are willing to follow and be able to complete all trial procedures
2. Subjects disease status of enrolment: not complete response (CR) after standard treatment; moderately to severely active autoimmune diseases
3. Age: ≥ 18 years old and ≤ 70 years old, male or female
4. Subjects with estimated survival > 12 weeks
5. Adequate organs function: Serum creatinine clearance meets relevant age/sex criteria,aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 times the upper limit of normal (ULN)
6. ECOG performance ≤ 2
7. Left ventricular ejection fraction (LVEF) ≥ 45%
8. Subjects have been treated with OCS in combination with an immunosuppressive or biologic agent for at least 2 weeks prior to enrollment

Exclusion Criteria:

1. Subjects with known severe allergic reactions, hypersensitivity, contraindication to any medications during the trial (cyclophosphamide, fludarabine, tozumabs), or subjects with a history of severe allergic reactions
2. Subjects with one of the following genetic syndromes: Fanconi syndrome, Kostmann syndrome, Shwachman syndrome or any of the known bone marrow failure syndromes
3. Subjects with active or uncontrolled infections requiring parenteral antimicrobials; evidence of severe active viral or bacterial infections or uncontrolled systemic fungal infections
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 other primary malignant tumors except: cured non-melanoma skin cancer or primary cervical cancer; subjects with inactive tumors
7. Subjects with more pronounced bleeding tendencies, such as gastrointestinal bleeding, coagulation disorders, and hypersplenism
8. Subjects were treated with systemic corticosteroids concomitantly within 2 weeks prior to treatment
9. Subjects with unstable angina, symptomatic congestive heart failure or myocardial infarction within the last 6 months
10. Females who are pregnant, lactating, or planning a pregnancy within six months
11. Subjects who have received other clinical trial treatment within 3 months
12. 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	Drug: anti-CD19 CAR NK cells; Patients will receive Fludarabine (30mg/m2 per day) and Cyclophosphamide (300mg/m2 per day) on day -5, -4, and -3, followed by Anti-CD19 CAR NK cells infusion.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease control rate of subjects	To characterize the efficacy of anti-CD19 CAR NK Cells for moderate to severe autoimmune diseases. Disease control is assessed according to SLEDAl 2K. Disease control rate is defined as proportion of patients with SRI-4 response: including SLEDAI 2K ≥ 4-Point improvement	4, 12, 24, and 52 weeks after infusion
Remission rate of subjects	To characterize the efficacy of anti-CD19 CAR NK Cells for moderate to severe autoimmune diseases. Remission is assessed according to SLEDAl 2K. Remission rate is defined as proportion of patients with SLEDAl 2K score= 0	4, 12, 24, and 52 weeks after infusion

Collaborators and Investigators

• Sponsor: YANRU WANG
• Collaborators: Rui Therapeutics Co., Ltd

Study record dates

Study Major Dates

• Study Start (Estimated): March 13, 2024
• Primary Completion (Estimated): March 13, 2025
• Study Completion (Estimated): March 13, 2026

Study Registration Dates

• First Submitted: March 12, 2024
• First Submitted That Met QC Criteria: March 13, 2024
• First Posted (Actual): March 19, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2024
• Last Update Submitted That Met QC Criteria: March 22, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases
• Other Study ID Numbers: 2023-11-01

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