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

Autoimmune Diseases Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06318533
• Other study ID #: 2023-11-01
• Status: Recruiting
• Phase: Early Phase 1
• Start date: March 13, 2024
• Est. completion date: March 13, 2026

Study information

• Verified date: March 2024
• Source: Affiliated Hospital of Jiangsu University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: March 13, 2026
• Est. primary completion date: March 13, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Autoimmune Diseases

Intervention

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.

Locations

Country	Name	City	State
China	Affiliated Hospital of Jiangsu University	Zhenjiang	Jiangsu
China	Jiangsu University Affiliated Hospital	Zhenjiang	Jiangsu

Sponsors (2)

Lead Sponsor	Collaborator
YANRU WANG	Rui Therapeutics Co., Ltd

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Secondary	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
Secondary	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