An Open-Label, Single-Arm Clinical Study to Evaluate the Safety and Preliminary Efficacy of CD20 Monoclonal Antibody Combined With NK042 Cell Injection in the Treatment of Multiple Sclerosis (MS).

An Open-Label, Single-Arm Clinical Study to Evaluate the Safety and Preliminary Efficacy of CD20 Monoclonal Antibody Combined With NK042 Cell Injection in the Treatment of Multiple Sclerosis (MS).

This is an Open-Label, Single-Arm Clinical Study to Evaluate the Safety and Preliminary Efficacy of CD20 Monoclonal Antibody Combined with NK042 Cell Injection in the Treatment of Multiple Sclerosis (MS).

The study will consist of a Screening Period of up to 4 weeks, a Treatment Period, and a 1-year Follow-up Period.

Inclusion criteria：

1. Able to understand research requirements, voluntary participation, and can provide written informed consent;
2. Age ≥18 years and ≤65 years;
3. Subjects diagnosed with relapsing-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS, with or without recurrence), or primary progressive multiple sclerosis (PPMS) according to the 2017 revision of McDonald's diagnostic criteria (SPMS diagnostic criteria include an initial relapsing-remitting course, subsequent disease progression with or without incidental relapse, mild remission, and plateau; Progress refers to the continuous deterioration of neurological impairment for at least 6 months);
4. Subjects in the Screening phase had an EDSS score of ≥2.5 and ≤6.5.
5. Subjects who weighed ≥ 45 kg and had a body mass index (BMI) of ≥ 18.0 kg/m2.

Exclusion criteria：

1. Subjects with a history of seizures or epilepsy (a history of febrile seizures in childhood was permitted);

2. Subjects with known clinical relapses (acute or subacute new or exacerbating neurological dysfunction with subsequent complete or partial recovery without fever or infection) within 8 weeks prior to enrollment;

3. Subjects with a history of neurological disorders other than MS, such as head trauma, cerebrovascular disease, and vascular dementia within 3 months;

4. Recent history of severe infection (e.g., infectious pneumonia, sepsis) within 4 weeks prior to screening; Infections requiring hospitalization or intravenous antibiotics, antiviral drugs, or antifungal drugs within 4 weeks prior to screening; Or a subject with a chronic bacterial infection (e.g., tuberculosis) determined by the investigator to be unacceptable;

5. Subjects with severe cognitive impairment, mental illness, other neurodegenerative disorders (such as Parkinson's disease or Alzheimer's disease), the presence of substance abuse or any other condition that would make a subject unsuitable for the study, or subjects the investigator believes may interfere with assessment or study completion;

6. Subjects with a history of attempted suicide or Grade 4 or 5 suicidal ideation on the Columbia Suicide Severity Rating Scale (C-SSRS) within 24 weeks prior to the screening visit, or subjects at risk for suicide as determined by the investigator;

7. Subjects with a history of unstable or severe heart, lung, tumor, liver, or kidney disease or other conditions of medical significance other than MS that prevented safe participation in the study;

8. Subjects who received live vaccine within 14 days prior to the screening visit or were scheduled to receive vaccine during the study;

9. Subjects who were HIV-positive;

10. Subjects with laboratory abnormalities at the screening visit:

    • alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3.0 × upper limit of normal (ULN)
    • Bilirubin > 1.5×ULN；; Unless the subject had a history of Gilbert syndrome (bilirubin > 1.5×ULN acceptable if bilirubin was split in two and direct bilirubin < 35%)
    • serum albumin < 3.5 g/dL
    • Estimated glomerular filtration rate < 60 mL/min/1.73 m2 (modified diet for patients with renal disease [MDRD])
    • other abnormal laboratory values or electrocardiogram (ECG) changes considered clinically significant at the investigator's discretion

11. Subjects with hepatitis B surface antigen (HBsAg) or anti-hepatitis B core antibody (HBcAb) at the screening visit or 12 weeks prior to the first study intervention. If the serological results are consistent with a resolved infection or vaccination, for example, the presence of HBsAb, it may not exclude potential subjects from the trial;

12. Subjects tested positive for hepatitis C antibodies at the screening visit or within 12 weeks prior to initiation of study drug administration. Note: Only subjects with positive hepatitis C antibodies due to previous disease remission after a confirmed negative hepatitis C ribonucleic acid (RNA) test were enrolled;

13. Use of immunomodulatory monoclonal antibodies or study drugs within 3 months or 5 half-lives prior to the Screening Period, whichever is higher;

14. The subject is known to be allergic to any component of study drug or any other NK cell injection drug;

15. Subjects who were positive for hepatitis B and C screening tests received live or attenuated vaccines within 6 weeks prior to baseline;

16. Subjects had MRI contraindications of pacemaker implantation, metal implants in high-risk areas (e.g., prosthetic heart valves, aneurysms/vascular clips), metal substances in high-risk areas (e.g., shrapnel), a known history of gadolinium allergy, or claustrophobia that would prevent completion of all MRI scans as defined in the protocol.

    Note: Patients with contraindication to gadolinium may be included in the study, but gadolinium developer shall not be used for MRI scanning;

17. Current or past medical history of primary immunodeficiency;

18. Subjects who were pregnant or lactating, or who were scheduled to become pregnant with severe psychiatric disorders during the study or within 12 months after the last dose, and were not eligible for follow-up;

19. Other circumstances that the investigator did not consider appropriate for participation in this study;

20. Subjects currently on any of the following drugs/treatments: aminopyridine/davapyridine, fingolimod, cladribine, cilimod, ponesimod, ozanimod, alemtuzumab, mitoxantrone, ocrelizumab, natalizumab, or similar approved but different trade names for MS, and any unapproved treatment or regimen for MS. Any new DMT approved after July 2022 and marketed at any time during the study.