F01 in the Treatment of Autoimmune Diseases

NCT06208280 | Unknown Phase 1

• 1 other identifier: SNC 103-CD19CAR NK-103
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicenter, open lable clinical study to evaluate the safety and tolerability of F01 in autoimmune diseases.

Conditions

Autoimmune Diseases

Keywords

NK; Autoimmune Diseases

Outcome Measures

Primary Outcomes (2)

• The proportion of subjects with AEs and SAEs

  The incidence and severity of all adverse events, serious adverse events, and abnormal laboratory test results

  Up to 12 weeks

• The proportion of subjects with DLT

  Incidence of DLT

  Up to 4 weeks

Secondary Outcomes (2)

• Efficacy of F01 cells in autoimmune diseases

  24 weeks after infusion

• Cellular kinetics

  96 weeks

Study Arms (1)

Assigned Interventions

EXPERIMENTAL

Drug: After preconditioning with Fludarabine and Cyclophosphamide, F01 will be evaluated.

Interventions

After preconditioning with Fludarabine and Cyclophosphamide, F01 will be evaluated. DRUG

Drug: After preconditioning with Fludarabine and Cyclophosphamide, F01 will be evaluated. 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)

Assigned Interventions

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.
• Special criteria for different indications:
• Patients with moderately to severely active SLE need to meet the following criteria：
• Diagnosis of systemic lupus erythematosus (SLE) according to the European League Against Rheumatology/American College of Rheumatology (EULAR/ACR) SLE classification criteria (Aringer et al 2019) at least 6 months prior to screening.
• Positive antinuclear antibody, and/or anti-double-stranded DNA antibody at screening.
• Moderate to severe activity is defined as: SLEDAI 2000 score ≥ 8 points at screening Disease remains active after at least 2 months of use of standard SLE treatment regimen prior to screening.
• Standard regimens for SLE include glucocorticoids and/or antimalarials, combined immunosuppressants/immunomodulators (including but not limited to azathioprine, mycophenolate mofetil, leflunomide, iratimod, methotrexate, cyclophosphamide, mycophenolate mofetil, cyclosporine, tacrolimus, etc.), and/or biologic agents (including but not limited to rituximab, belimumab, telitacicept, etc.).
• Patients with relapsed or refractory AAV should meet the following criteria：
• Clinical diagnosis of granulomatosis with polyangitis (GPA) and microscopic polyangiitis (MPA) as defined by the 2012 Chapel Hill Consensus Conference (CHCC); At least one major item, or at least three other items, in Birmingham Vasculitis Activity Score (BVAS) version 3; Positive anti-protease-3 (PR3-ANCA) or antimyeloperoxidase (MPO-ANCA) at screening;
• Relapsed/refractory is defined as:
• Subjects with relapsed AAV: At least 1 disease recurrence (defined as the presence of at least one important item on the BVAS assessment, or at least 3 other items) after at least 3 months of treatment with glucocorticoids in combination with immunosuppressants (cyclophosphamide, rituximab, azathioprine, methotrexate, mycophenolate mofetil, etc.) (BVAS score 0 and glucocorticoid dose ≤ 7.5 mg/day prednisone or other equivalent glucocorticoid drugs) or 1-2 new items in two consecutive assessments), and disease recurrence occurred within 12 weeks prior to screening; Subjects with refractory AAV: Glucocorticoids combined with immunosuppressants (cyclophosphamide, rituximab, azathioprine, methotrexate, mycophenolate mofetil, etc.) for at least 3 months have not been effective (BVAS score of 0 and glucocorticoid dose ≤ 7.5 mg/day prednisone or other equivalent glucocorticoid drugs); 2.3 Patients with moderately to severely active IIM need to meet the following criteria： According to the 2017 EULAR/ACR classification criteria, the probability of diagnosing IIM is ≥55%, and it is classified as dermatomyositis (DM), polymyositis (PM), or immune-mediated necrotizing myopathy (IMNM) based on age at first onset, skin and muscle strength performance, laboratory tests, and muscle biopsy features;
• Disease activity/severity meets the following criteria:
• MMT-8 score ≤141 out of 150;
• At least 2 of the other CSMs exceptions are met:
• Patient-assessed overall activity (based on visual analogue scale (VAS) score≥2 points (range 0-10 points); Physician-assessed overall disease activity VAS score ≥2 points (range 0-10 points); Extramuscular global mobility VAS score ≥2 points (range 0-10 points); Health Assessment Questionnaire (HAQ) score ≥0.25 (range 0-3). At least 1 muscle enzyme level \> 1.5 times ULN. - Prior intolerance or inadequate response to treatment with glucocorticoids and at least one other immunosuppressant or modulator, requiring that: Treatment with glucocorticoids and at least 2 immunosuppressants (azathioprine, methotrexate, mycophenolate mofetil, etc.) at known effective doses for at least 3 months; 2.4 Subjects with relapsed/refractory active diffuse cutaneous systemic sclerosis (dcSSc) need to meet the following criteria：

You may not qualify if:

• Severe pulmonary disease in the past 1 year, such as moderate to severe pulmonary hypertension (echocardiographic mean pulmonary artery pressure \> 60 mmHg), requiring oxygen storage mask oxygen therapy or non-invasive or invasive ventilator to assist breathing at screening Primary central nervous system lymphoma; SLE subjects need to exclude subjects who have had lupus crisis in the past 3 months, active central nervous system lupus, severe hemolytic anemia, severe thrombocytopenic purpura, severe neutropenia, severe myocardial damage, severe lupus pneumonia or pulmonary hemorrhage, severe lupus hepatitis, severe vasculitis;
• Combined with severe kidney disease, including severe lupus nephritis, severe nephrotic syndrome, etc. Severe is defined as:
• Have received any of the following treatments within the specified time: Previous kidney transplantation; Dialysis or plasmapheresis within 3 months prior to screening; Pulse glucocorticoid therapy (defined as a dose ≥ 500 mg/d prednisone or equivalent dose of other glucocorticoids) within 1 month prior to screening;
• Need to receive either of the following treatments during the study: Need to use protocol prohibited medications; Need for dialysis or plasmapheresis; Kidney transplantation is required or planned.
• Patients who have received the following treatments within the prescribed time frame prior tolymphodepletion pretreatment:
• Received autologous/allogeneic hematopoietic stem cell transplantation or CAR-T and other cell therapy; Pulse glucocorticoid therapy within 2 months (defined as a dose of ≥500 mg/day prednisone or equivalent dose of other glucocorticoids); Have been treated with biologics such as belimumab or telitacicept within 1 month; Received major surgery, received live vaccine or received other clinical study treatment within 1 month; Presence of uncontrolled active infection requiring treatment with systemic antibiotics, antiviral, or antifungal drugs within 14 days, except for prophylactic therapy.
• prednisone or equivalent glucocorticoids should be reduced to ≤20 mg/day at least 7 days before lymphodepletion Concomitant active hepatitis B (HBV), hepatitis C (HCV), human immunodeficiency virus infection (HIV), or syphilis infection.
• Risk of active tuberculosis at screening, regardless of completion of adequate treatment: 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; Use of drug combinations/combination therapies prohibited by the protocol during screening; Any situations that the investigator believes the patients are not suitable for the study.

Sponsors & Collaborators

• RenJi Hospital: lead
• Shanghai Simnova Biotechnology Co.,Ltd.: collaborator

Study Sites (1)

Department of Rheumatology, Ren Ji Hospital South Campus, School of Medicine, Shanghai JiaoTong University

Shanghai, Shanghai Municipality, 200001, China

RECRUITING

MeSH Terms

Conditions

Autoimmune Diseases

Interventions

fludarabine; Cyclophosphamide

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Central Study Contacts

Qiong Fu, Ph.D

CONTACT

86-13585603288; Fuqiong5@163.com

Study Design

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

Study Record Dates

• First Submitted: January 5, 2024
• First Posted: January 17, 2024
• Study Start: January 9, 2024
• Primary Completion: January 1, 2025
• Study Completion: December 1, 2025
• Last Updated: January 17, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)