F01 in the Treatment of Moderate-to-severe Refractory Systemic Lupus Erythematosus

NCT06468683 | Not Yet Recruiting Phase 1

• 1 other identifier: SNC 103-CD19CAR NK-104
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase I clinical study to evaluate the safety , pharmacokinetic profile, and preliminary efficacy of F01 in patients with moderate-to-severe refractory systemic lupus erythematosus.

Conditions

Lupus Erythematosis

Keywords

Moderate-to-severe refractory systemic lupus erythematosus

Outcome Measures

Primary Outcomes (2)

• Primary Outcome Measures

  The proportion of subjects with AEs and SAEs

  12 weeks

• Primary Outcome Measures

  The proportion of subjects with DLT

  4 weeks

Secondary Outcomes (8)

• Secondary Outcome Measures

  48 weeks

• Secondary Outcome Measures

  96 weeks

• Secondary Outcome Measures

  96 weeks

• Secondary Outcome Measures

  96 weeks

• Secondary Outcome Measures

  96 weeks

Other Outcomes (3)

• Exploratory

  96 weeks

• Exploratory

  96 weeks

• Exploratory

  96 weeks

Study Arms (1)

Experimental: After preconditioning with chemotherapy, F01 will be evaluated.

EXPERIMENTAL

Assigned Interventions

Biological: After preconditioning with chemotherapy, F01 will be evaluated.

Interventions

After preconditioning with chemotherapy, F01 will be evaluated. BIOLOGICAL

Biological: 0.5-3×10\^9 CAR+NK Cells, Treatment follows a lymphodepletion Drug: Fludarabine: 25-30 mg/m\^2 (D-5\~D-3) Drug: Cyclophosphamide: 250-300 mg/ m\^2 (D-5\~D-3)

Experimental: After preconditioning with chemotherapy, F01 will be evaluated.

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 and ≤65 years old, gender unlimited.
• Subjects with moderate-to-severe refractory SLE must meet all of the following criteria:
• Diagnosis of SLE at least 24 weeks prior to screening in accordance with the European Federation of Rheumatological Societies (EULAR)/American College of Rheumatology (ACR) 2019 SLE classification criteria at screening;
• Applicants must meet one of the following criteria at screening: a. positive for antinuclear antibody (ANA); b. Positive anti-dsDNA antibody;c. Positive anti-Smith antibody;
• SLEDAI-2000 score ≥ 8 at screening
• Have received adequate standard doses of glucocorticoids, antimalarials, immunosuppressants/immunomodulators, and at least one biologic agent for at least 2 months prior to screening, with a stable dose \> disease remaining active after 2 weeks of treatment. Oral glucocorticoids must meet the following requirements: 1) Prednisone (or equivalent) ≥ 7.5 mg/day and ≤ 60 mg/day. 2) When used in combination with immunosuppressants and/or biologics, there is no minimum daily dose requirement for glucocorticoids. The blood routine within 7 days of clear drenching conditioning chemotherapy meets the following requirements:
• Absolute neutrophil value (ANC) ≥ 1.5×109/L;
• Hemoglobin (Hb) ≥ 80g/L;
• Platelet count (PLT) ≥ 50×109/L.
• Adequate hepatic, renal, lung, and cardiac function, defined as:
• Serum ALT and AST ≤ 2.5 times the upper limit of normal;
• Total bilirubin ≤ 1.5 times the upper limit of normal, except for patients with Gilbert\'s syndrome, where total bilirubin must be ≤ 3.0 times the upper limit of normal;
• creatinine clearance (estimated by Cockcroft Gault\'s formula) (Appendix 1) ≥ 50 ml/min;
• Oxygen saturation of ≥ 92% in non-oxygenated conditions under indoor ventilation; No clinically significant pleural effusion;
• Left ventricular ejection fraction ≥ 50%; Echocardiography to confirm the absence of pericardial effusion; There were no clinically significant abnormal findings on ECG.

You may not qualify if:

• Known allergies, hypersensitivity, intolerance, or contraindications to F01 or any ingredient of drugs that may be used in the study (including fludarabine, cyclophosphamide, tocilizumab), or subjects who have had severe allergic reactions in the past.
• Severe lupus nephritis (defined as urine protein \>6g/24 hours or serum creatinine \>2.5mg/dL or 221μmol/L) within 3 months prior to screening, or requiring active nephritis with drugs prohibited by the protocol, or requiring hemodialysis or treatment with prednisone ≥100mg/d or equivalent glucocorticoids ≥for 14 days.
• Previous history or pathological changes of clinically significant central nervous system disease, including but not limited to lupus encephalopathy, seizures, cerebrovascular accident (ischemia/hemorrhage), dementia, cerebellar disease, organic encephalopathy syndrome, encephalitis, central nervous system vasculitis, or psychiatric disease.
• Combined with severe pulmonary diseases, such as pulmonary hypertension with World Health Organization functional classification ≥ level 3, requiring oxygen therapy with an oxygen storage mask or non-invasive or invasive ventilator to assist breathing at screening;
• Unstable cardiovascular function:
• Myocardial infarction within 6 months prior to screening;
• Unstable angina within 3 months prior to screening;
• Uncontrolled, clinically significant cardiac arrhythmias (e.g., sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes);
• Mobitz type II. second-degree or third-degree atrioventricular block;
• New York Cardiac Function Association Class ≥ 3 congestive heart failure;
• Poorly controlled hypertension (systolic blood pressure \> 160 mmHg and/or diastolic blood pressure \> 100 mmHg) or concomitant hypertensive crisis or hypertensive encephalopathy;
• Patients with a history of concomitant malignancy, including tumor-associated polymyositis/dermatomyositis. Patients with non-melanoma skin cancer, carcinoma in situ of the cervix, local prostate cancer, low-stage bladder cancer, ductal carcinoma in situ, or patients who have no evidence of recurrence in the past 2 years and do not need treatment are excluded.
• Uncontrolled active bacterial, viral, fungal, mycobacterial infection or other infections requiring treatment with intravenous antibiotics, antiviral or antifungal drugs within 14 days prior to drenching conditioning chemotherapy; However, these drugs can be used for prophylactic treatment (including intravenous use).
• Risk of active tuberculosis at screening, regardless of completion of adequate treatment, including the presence of signs or symptoms of active tuberculosis (such as fever, cough, night sweats, and weight loss) as judged by the investigator at screening; Chest imaging (e.g., chest x-ray, chest CT scan) documented at screening or at any time within 6 months prior to screening showing active tuberculosis; Evidence of latent tuberculosis infection, such as a positive γ-interferon release test, at screening.
• Active hepatitis B virus (HBV), hepatitis C virus (HCV) infection at screening. Subjects who are HBsAg positive and/or HBcAb positive but HBV-DNA negative, and/or HCVAb positive but HCV-RNA negative are allowed to be enrolled (if the site report includes a range of reference values, the upper limit of normal for HBV-DNA and HCV-RNA tests is based on the test values of each site, and higher than the upper limit of test values is defined as \"positive\"; If the site report only shows \"negative/positive\", the positive is based on the test report result).

Sponsors & Collaborators

• Shanghai Simnova Biotechnology Co.,Ltd.: lead

Study Sites (1)

Shanghai jiaotong University School of Medicine,Renji Hospital

Shanghai, Shanghai Municipality, 200000, China

Location

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

Drug Therapy

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Central Study Contacts

Director Clinical Trial Disclosure Simnova Director Clinical Trial Disclosure Simnova

CONTACT

021-68099999; Disclosure@simnovabio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2024
• First Posted: June 21, 2024
• Study Start: June 15, 2024
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: June 21, 2024

Record last verified: 2024-05

Locations

CN (1)