An Exploratory Clinical Study of CD19 CAR NK Cells for the Treatment of Refractory Antisynthetase Antibody Syndrome and Rheumatoid Arthritis

An Exploratory Clinical Study of the Safety and Efficacy of CD19 Chimeric Antigen Receptor NK Cells for the Treatment of Refractory Antisynthetase Antibody Syndrome and Rheumatoid Arthritis

A single-center, open-label dose-escalation design to evaluate the safety and efficacy of 3 infusions of anti CD19 CAR NK cells (KN5501), as well as the expansion and persistence of KN5501 in patients with refractory antisynthetase antibody syndrome (ASyS) and rheumatoid arthritis (RA); To evaluate the ability of KN5501 to clear CD19-positive B cells in patients to determine the feasibility of KN5501 for the treatment of refractory ASyS and or RA.

Study Overview

• Status: Recruiting
• Conditions: Rheumatoid Arthritis; Antisynthetase Syndrome
• Intervention / Treatment: Biological: anti CD19 CAR NK cells

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Wenfeng Tan, PhD, MD; Phone Number: 086 18061202878; Email: tanwenfeng@jsph.org.cn
• Study Contact Backup: Name: Hanxiao You, PhD, MD; Phone Number: 086 18800181269; Email: youhanxiao@jsph.org.cn

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Recruiting
      • The First Affiliated Hospital with Nanjing Medical University
      • Contact: Wenfeng Tan, PhD, MD; Phone Number: 086 18061202878; Email: tanwenfeng@jsph.org.cn
      • Contact: Hanxiao You, PhD, MD; Phone Number: 086 18800181269; Email: youhanxiao@jsph.org.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Subjects voluntarily sign the Informed Consent Form (ICF) , participate in this clinical study and be willing to follow and be able to complete all trial procedures.
2. Defined according to the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria, adult patients with RA diagnosed ≥3 months prior to screening;Moderately to severely active RA;Poor response, or loss of response, or intolerance to at least one conventional synthetic DMARD (csDMARD) or biologic DMARD (bDMARD) or targeted synthetic DMARD (tsDMARD).
3. Defined according to the 2020 ENMC-DM classification diagnostic criteria. Adult patients with ASyS diagnosed ≥3 months prior to screening; patients with moderately severe active ASyS.
4. Age: ≥ 18 years old and ≤ 70 years old, male or female.
5. Subjects with estimated survival > 12 weeks.
6. Serum creatinine clearance meets the relevant age/sex criteria, and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 times the upper limit of normal (ULN).
7. ECOG score 0 - 2.
8. The heart structure is essentially normal by echocardiography and Left ventricular ejection fraction (LVEF) ≥45%.
9. 2 weeks after the subject received the last dose treatment (hormonal, immunosuppressive or other experimental treatment).

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. Subjects with history of malignancy except cured of carcinoma in situ of the skin or cervix, and patients with inactive tumors.
7. Subjects with pronounced bleeding tendencies, such as gastrointestinal bleeding, coagulation disorders, and hypersplenism.
8. The subject with unstable angina, symptomatic congestive heart failure or myocardial infarction within the last 6 months.
9. Females who are pregnant, lactating, or planning a pregnancy within six months.
10. Subjects who have received other clinical trial treatment within 3 months.

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

Biological: anti CD19 CAR NK cells; This study is a single-arm, open-label and single-center exploratory clinical study to evaluate the safety and effectiveness of anti CD19 CAR NK cells in patients with refractory antisynthetase antibody syndrome (ASyS) and rheumatoid arthritis (RA). All subjects will receive fludarabine/cyclophosphamide lymphodepletion followed by Anti-CD19 CAR NK cells infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Dose-Limiting Toxicity (DLT)	To characterize the safety of CD19 CAR NK Cells (KN5501) for refractory antisynthetase antibody syndrome (ASyS) and rheumatoid arthritis (RA)	up to 52 weeks after infusion
Incidence of Treatment Emergent Adverse Events (TEAEs)	To characterize the safety of CD19 CAR NK Cells (KN5501) for refractory antisynthetase antibody syndrome (ASyS) and rheumatoid arthritis (RA)	up to 52 weeks after infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The overall response rate (ORR)	To characterize the efficacy of CD19 CAR NK Cell (KN5501) for refractory antisynthetase antibody syndrome (ASyS) and rheumatoid arthritis (RA)	4, 12, 24, 36 and 52 months after infusion

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital with Nanjing Medical University
• Collaborators: Rui Therapeutics Co., Ltd

Study record dates

Study Major Dates

• Study Start (Estimated): May 20, 2025
• Primary Completion (Estimated): October 20, 2025
• Study Completion (Estimated): October 20, 2026

Study Registration Dates

• First Submitted: September 23, 2024
• First Submitted That Met QC Criteria: September 23, 2024
• First Posted (Actual): September 26, 2024

Study Record Updates

• Last Update Posted (Actual): April 30, 2025
• Last Update Submitted That Met QC Criteria: April 26, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Pathologic Processes; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Disease; Arthritis; Syndrome; Arthritis, Rheumatoid
• Other Study ID Numbers: 2023-SR-834

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