Efficacy and Safety of HN2301 in Autoimmune Diseases（AIDs）

Official title

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）

Overview

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

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.).

Interventions

• 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.

Primary outcome measures

• Incidence of treatment-emergent adverse events (TEAEs) [Time frame: Up to 3 months]

Secondary outcome measures (12)

• vivo CAR T cell production [Time frame: Day-28 to14 days]
• B cell ratio and counts in peripheral blood [Time frame: Day-28 to12 months]
• Change from baseline of SLEDAI-2K score after HN2301 administration. [Time frame: Day-28 to12 months]
• Quantify the clinical activity of HN2301 in patients using Physician Global Assessment (PGA) . [Time frame: Day-28 to12 months]
• Proportion of participants achieving lupus low disease activity status (LLDAS) [Time frame: Day-28 to12 months]
• Proportion of patients achieving DORIS remission after HN2301 administration [Time frame: Day-28 to12 months]
• Assess the clinical activity of HN2301 in patients with SLE using Systemic Lupus Erythematosus Responder Index-4 (SRI-4) [Time frame: Day-28 to12 months]
• Proportion of patients achieving complete renal response (CRR) after HN2301 administration [Time frame: Day-28 to12 months]
• Changes from baseline in Patient Global Assessment（PtGA） scores [Time frame: Up to 12 months]
• Change from baseline in modified Rodnan Skin Score (mRSS) [Time frame: Up to 12 months]
• Changes from baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) score [Time frame: Up to 12 months]
• Change from baseline in revised Composite Response Index in Systemic Sclerosis (r-CRISS) score [Time frame: Up to 12 months]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The First Affiliated Hospital of University of Science and Technology of China — Hefei

Identifiers

NCT: NCT06801119 · HN2301-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗