Using CD19 CAR NK cells to treat 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

This study tests if a new treatment using special immune cells can help people with tough cases of antisynthetase antibody syndrome and rheumatoid arthritis feel better.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: The First Affiliated Hospital with Nanjing Medical University (Academic / other)
• Drugs / interventions: cyclophosphamide, fludarabine
• Locations: 1 site (Nanjing, Jiangsu)
• Trial ID: NCT06613490 on ClinicalTrials.gov

What this trial studies

This clinical study evaluates the safety and efficacy of three infusions of anti CD19 CAR NK cells (KN5501) in patients with refractory antisynthetase antibody syndrome and rheumatoid arthritis. It employs a single-center, open-label, dose-escalation design to assess the treatment's ability to clear CD19-positive B cells and its overall impact on disease symptoms. The study aims to determine the expansion and persistence of KN5501 in the patient population over the course of treatment.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 to 70 with moderately to severely active rheumatoid arthritis or antisynthetase antibody syndrome who have not responded to previous treatments.

Not a fit: Patients with mild forms of rheumatoid arthritis or antisynthetase antibody syndrome, or those who have not been diagnosed for at least three months, may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients suffering from refractory antisynthetase antibody syndrome and rheumatoid arthritis.

How similar studies have performed: While this approach is novel, similar studies using CAR NK cells have shown promise in other conditions, indicating potential for success.

Eligibility criteria

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.

Where this trial is running

Nanjing, Jiangsu

• The First Affiliated Hospital with Nanjing Medical University — Nanjing, Jiangsu, China (Recruiting)

Study contacts

• Study coordinator: Wenfeng Tan, PhD, MD

Conditions Antisynthetase Syndrome; Rheumatoid Arthritis