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).

Study Overview

• Status: Not yet recruiting
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Biological: NK042; Drug: ofatumumab

Detailed Description

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

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Yong Zhang, MD; Phone Number: +86 18052268193; Email: zy20037416@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Combination Therapy Group; All participants in this single-arm study will receive the combined intervention, which consists of a standard regimen of a CD20 monoclonal antibody administered concurrently with NK042 cell injection (an allogeneic natural killer cell therapy). The dose level of NK042 cells will be escalated sequentially across participant cohorts following safety assessment.

Biological: NK042; NK042 is an allogeneic, off-the-shelf cellular therapy derived from healthy donors and enriched with NKR+ NK cells。; Drug: ofatumumab; Ofatumumab is a fully human monoclonal antibody targeting the CD20 antigen on the surface of B lymphocytes. In this study, it will be administered in combination with the investigational NK042 cell injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse events (AEs) and Serious Adverse Events (SAEs)	Number of subjects experiencing adverse events, and the frequency and severity of adverse events. The type, frequency, onset, and severity of treatment-emergent adverse events (TEAEs) will be assessed in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE),version 5.0.	Up to 48 weeks after first dose of NK042.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Expanded Disability Status Scale (EDSS) Score	Change in Expanded Disability Status Scale (EDSS) score from baseline to Week 24。	Baseline to week 24

Collaborators and Investigators

• Sponsor: The Affiliated Hospital of Xuzhou Medical University
• Investigators: Principal Investigator: Yong Zhang, MD, The Affiliated Hospital of Xuzhou Medical University; Principal Investigator: Fudong Shi, MD, The General Hospital of Tianjin Medical University/Beijing tiantan Hospital; Principal Investigator: Guiyun Cui, MD, The Affiliated Hospital of Xuzhou Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2028

Study Registration Dates

• First Submitted: March 24, 2026
• First Submitted That Met QC Criteria: April 20, 2026
• First Posted (Actual): April 22, 2026

Study Record Updates

• Last Update Posted (Actual): April 22, 2026
• Last Update Submitted That Met QC Criteria: April 20, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Multiple Sclerosis; NK cell therapy; CD20 monoclonal antibody; Cell immunotherapy; Multiple sclerosis (MS)、NK cell therapy、CD20 monoclo、Cell immunotherapynal antibody、
• Additional Relevant MeSH Terms: Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis; ofatumumab
• Other Study ID Numbers: NK042-MS-IIT-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No