Rheumatoid Arthritis, Scleroderma, Systemic Lupus Erythematosus
Conditions
Keywords
SLE, SSc,RA
Brief summary
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
DRUGHN2301 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.
Sponsors
Shenzhen MagicRNA Biotechnology Co., Ltd
The First Affiliated Hospital of University of Science and Technology of China
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 69 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of treatment-emergent adverse events (TEAEs) | Up to 3 months | Incidence, nature, and severity of treatment-emergent adverse events, assessed according to the study protocol and applicable toxicity grading criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quantify the clinical activity of HN2301 in patients using Physician Global Assessment (PGA) . | Day-28 to12 months | 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. |
| Proportion of participants achieving lupus low disease activity status (LLDAS) | Day-28 to12 months | Proportion of participants who achieve LLDAS at scheduled visits through Month 12. |
| Proportion of patients achieving DORIS remission after HN2301 administration | Day-28 to12 months | Assessment of DORIS response rate at various timepoints up to the month 12 follow-up visit. |
| Assess the clinical activity of HN2301 in patients with SLE using Systemic Lupus Erythematosus Responder Index-4 (SRI-4) | Day-28 to12 months | 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. |
| Proportion of patients achieving complete renal response (CRR) after HN2301 administration | Day-28 to12 months | Proportion of patients achieving complete renal response (CRR) after HN2301 administration |
| Changes from baseline in Patient Global Assessment（PtGA） scores | Up to 12 months | 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. |
| Change from baseline in modified Rodnan Skin Score (mRSS) | Up to 12 months | 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. |
| Changes from baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) score | Up to 12 months | 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). |
| Change from baseline in revised Composite Response Index in Systemic Sclerosis (r-CRISS) score | Up to 12 months | 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. |
| Changes from baseline in Disease Activity Score (DAS28) score | Up to 12 months | 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. |
| Changes from baseline in Visual Analogue Scale (VAS) score | Up to 12 months | A total score can fall between 0 and 10 |
| vivo CAR T cell production | Day-28 to14 days | CAR T production in the peripheral blood of AID patients, by flow cytometry (FACS), and quantitative polymerase chain reaction (qPCR) in peripheral blood |
| Change from baseline of SLEDAI-2K score after HN2301 administration. | Day-28 to12 months | 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. |
| B cell ratio and counts in peripheral blood | Day-28 to12 months | 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 |
Countries
China
Contacts
CONTACTZhu Chen, MD
CONTACTZe Xiu Xiao, MD
PRINCIPAL_INVESTIGATORZhu Chen, MD
The First Affiliated Hospital of University of Science and Technology of China
Outcome results
None listed