Efficacy and Safety of HN2301 in Autoimmune Diseases（AIDs） (SLE，SSc，RA)

Dose-escalation Study to Assess the Safety, Tolerability, and Preliminary Efficacy of HN2301 in Patients With Autoimmune Diseases Including Systemic Lupus Erythematosus（SLE）, Systemic Sclerosis (SSc) and Rheumatoid Arthritis （RA）

This is an open lable and single arm study, is designed to evaluate the safety and preliminary efficacy of HN2301 in Autoimmune Disease（AID）

Study Overview

• Status: Recruiting
• Conditions: Rheumatoid Arthritis; Systemic Lupus Erythematosus; Scleroderma
• Intervention / Treatment: Drug: HN2301 injection

Detailed Description

This study is a prospective exploratory clinical trial in subjects with Autoimmune Disease（SLE, SSc, RA, etc.）. The objective is to evaluate the safety and efficacy of HN2301 injection in Autoimmune Disease (SLE, SSc, RA, etc.).

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Zhu Chen, MD; Phone Number: +86055162284920; Email: doczchen@ustc.edu.cn
• Study Contact Backup: Name: Ze Xiu Xiao, MD; Phone Number: +86075527109036; Email: xiaozexiu@magicrna.com

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China
      • Recruiting
      • The First Affiliated Hospital of University of Science and Technology of China
      • Contact: Zhu Chen, MD; Phone Number: +86055162284920; Email: doczchen@ustc.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients aged between 18 and 69 (inclusive), of any gender;
• Appropriate bone marrow, coagulation, cardiopulmonary, liver, and kidney functions. Bone marrow function: ANC ≥1.5×10^9/L, ALC ≥0.8×10^9/L, Hb ≥80g/L. No use of transfusions and growth factors allowed within 7 days prior to screening to meet these requirements. Coagulation function: INR or APTT ≤1.5×ULN. Cardiac function: Echocardiography (ECHO) assessment of left ventricular ejection fraction (LVEF) ≥40%. Lung function: ≤CTCAE grade 1 dyspnea and SpO2 ≥92% (measured by pulse oximetry) while breathing indoor air. Liver function: ALT and AST ≤2.5×ULN, total bilirubin <2.0mg/dL (Gilbert syndrome subjects total bilirubin <3.0mg/dL). Kidney function: defined as creatinine clearance rate (Cockcroft-Gault) ≥50mL/min without need for fluid assistance;
• Non-pregnant/non-lactating participants, willing to adopt contraceptive measures within 12 months after drug infusion;
• Diagnosed with SLE according to the 2019 EULAR/ACR SLE diagnostic criteria; A history of SLE for at least 6 months, having used a stable standard treatment regimen for at least 8 weeks; Oral corticosteroids are prednisone (or equivalent drug) ≥7.5mg/day and ≤30mg/day. At least two immunosuppressants have been used in a standardized manner (including hydroxychloroquine); Screening period tests meet: positive blood antinuclear antibody (ANA), and/or positive anti-ds-DNA antibodies, and/or hypocomplementemia;
• SSc-meets the classification criteria of ACR and EULAR, 10-35 in mRSS score;
• RA-meets the classification criteria of ACR and EULAR, DAS28-ESR>3.2, ACPA possitive.

Exclusion Criteria:

• Individuals with positive Hepatitis B surface antigen (HBsAg) and/or Hepatitis B core antibody (HBcAb), and Hepatitis B virus (HBV) DNA positivity or titers above the detection threshold; those with positive Hepatitis C virus (HCV) antibodies and HCV RNA positivity or titers above the detection threshold; individuals with Human Immunodeficiency Virus (HIV) antibodies positivity, CMV DNA positivity or above the detection limit; those with positive syphilis antigen or antibodies;
• Presence of other uncontrolled active infections;
• History of major organ transplantation (such as heart, lung, liver, kidney) or bone marrow/hematopoietic stem cell transplantation;
• Pregnant or breastfeeding women;
• Receiving any mRNA-LNP product or other LNP medications within the past two years;
• History of any of the following cardiovascular diseases within the last 6 months before screening: Class III or IV heart failure defined by the New York Heart Association (NYHA), myocardial infarction, unstable angina, uncontrolled or symptomatic atrial arrhythmias, any ventricular arrhythmias, or other clinically significant cardiac diseases;
• History of live vaccine administration within the last 30 days;
• Individuals with asthma, severe allergies;
• Other conditions deemed inappropriate for participation in this clinical study by the investigator.

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: HN2301 treatment group; Participants will receive HN2301 Injection at the specified dose level and on the specified study days.	Drug: HN2301 injection; Dosing will begin at a lower dose level and may be escalated to dose levels considered safe and potentially effective according to the study protocol.; Other Names: in vivo cart

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment-emergent adverse events (TEAEs)	Incidence, nature, and severity of treatment-emergent adverse events, assessed according to the study protocol and applicable toxicity grading criteria.	Up to 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
B cell ratio and counts in peripheral blood	Assessment of B cell ratio and counts (B cell counts per μl peripheral blood) and B cell subsets(naive B cell, memory B cell) by flow cytometry (FACS) in peripheral blood	Day-28 to12 months
Change from baseline of SLEDAI-2K score after HN2301 administration.	Assessment of Systemic Lupus Erythematosus Disease Activity Index 2000 from baseline administration at various timepoints up to month 12 follow-up visit. A total score can fall between 0 and 105, with a higher score representing a more significant degree of disease activity.	Day-28 to12 months
Proportion of patients achieving DORIS remission after HN2301 administration	Assessment of DORIS response rate at various timepoints up to the month 12 follow-up visit.	Day-28 to12 months
Assess the clinical activity of HN2301 in patients with SLE using Systemic Lupus Erythematosus Responder Index-4 (SRI-4)	Assessment of whether participants meet the Systemic Lupus Erythematosus Responder Index-4 (SRI-4) criteria (yes/no) at various timepoints up to the month 12 follow-up visit.	Day-28 to12 months
Proportion of patients achieving complete renal response (CRR) after HN2301 administration	Proportion of patients achieving complete renal response (CRR) after HN2301 administration	Day-28 to12 months
vivo CAR T cell production	CAR T production in the peripheral blood of AID patients, by flow cytometry (FACS), and quantitative polymerase chain reaction (qPCR) in peripheral blood	Day-28 to14 days
Quantify the clinical activity of HN2301 in patients using Physician Global Assessment (PGA) .	Assessment of Physician Global Assessment (PGA) from baseline administration at various timepoints up to month 12 follow up visit. A total score can fall between 0.0 and 3.0, with a higher score representing a more significant degree of disease activity.	Day-28 to12 months
Proportion of participants achieving lupus low disease activity status (LLDAS)	Proportion of participants who achieve LLDAS at scheduled visits through Month 12.	Day-28 to12 months
Change from baseline in modified Rodnan Skin Score (mRSS)	Assessment of change from baseline in modified Rodnan Skin Score (mRSS). Total scores range from 0 to 51, with higher scores indicating greater skin thickening.	Up to 12 months
Changes from baseline in Patient Global Assessment（PtGA） scores	Assessment of change from baseline in Patient Global Assessment (PtGA) of overall disease activity at scheduled visits through Month 12，typically on a 0 to 10 numeric scale, where 0 indicates no disease activity and 10 represents the worst possible activity.	Up to 12 months
Changes from baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) score	Assessment of change from baseline in Health Assessment Questionnaire Disability Index (HAQ-DI), a patient-reported measure of functional ability across 8 domains, the patient responds on a scale of 0 (no disability) to 3 (completely disabled).	Up to 12 months
Change from baseline in revised Composite Response Index in Systemic Sclerosis (r-CRISS) score	Assessment of change from baseline in the revised Composite Response Index in Systemic Sclerosis (r-CRISS), a weighted composite score based on 5 core measures of disease status, improved by a certain percentage in ≥3 of 5 core set measures.	Up to 12 months
Changes from baseline in Disease Activity Score (DAS28) score	Proportion of patients disease activity changes, a scale from 0 to 10 indicating the current activity of the rheumatoid arthritis. A DAS28 above 5.1 means high disease activity whereas a DAS28 below 3.2 indicates low disease activity.	Up to 12 months
Changes from baseline in Visual Analogue Scale (VAS) score	A total score can fall between 0 and 10	Up to 12 months

Collaborators and Investigators

• Sponsor: Shenzhen MagicRNA Biotechnology Co., Ltd
• Collaborators: The First Affiliated Hospital of University of Science and Technology of China
• Investigators: Principal Investigator: Zhu Chen, MD, The First Affiliated Hospital of University of Science and Technology of China

Study record dates

Study Major Dates

• Study Start (Actual): March 16, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: January 15, 2025
• First Submitted That Met QC Criteria: January 23, 2025
• First Posted (Actual): January 30, 2025

Study Record Updates

• Last Update Posted (Actual): April 28, 2026
• Last Update Submitted That Met QC Criteria: April 26, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: SLE, SSc,RA
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Scleroderma, Systemic; Lupus Erythematosus, Systemic; Scleroderma, Diffuse; Arthritis, Rheumatoid
• Other Study ID Numbers: HN2301-01

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
• product manufactured in and exported from the U.S.: No