Autoimmune Disease, Systemic Lupus Erythematosus, Systemic Sclerosis (SSc)
Conditions
Keywords
SLE, SSc
Brief summary
This is an open-label, single-arm study designed to evaluate the safety and preliminary efficacy of HN2302 in patients with autoimmune diseases, including systemic lupus erythematosus (SLE) and systemic sclerosis (SSc).
Detailed description
The study consists of a screening period of up to 4 weeks, a treatment period, and a follow-up period of 1 year.
Interventions
DRUGHN2302 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
* Adults aged 18 to 69 years, regardless of gender. * Adequate bone marrow, coagulation, cardiopulmonary, hepatic, and renal function. * Participants who are not pregnant or breastfeeding and who agree to use effective contraception for 12 months after drug infusion, if applicable. * Diagnosis of systemic lupus erythematosus (SLE) according to the 2019 EULAR/ACR classification criteria, with a history of SLE for at least 6 months; during screening, participants must have positive antinuclear antibody (ANA), and/or positive anti-double-stranded DNA antibody, and/or hypocomplementemia. * Diagnosis of systemic sclerosis (SSc) according to the 2013 ACR/EULAR classification criteria, including limited cutaneous or diffuse cutaneous systemic sclerosis, with new or progressive skin manifestations within 6 months before screening.
Exclusion criteria
* Positive hepatitis B surface antigen (HBsAg), or positive hepatitis B core antibody (HBcAb) with detectable or quantifiable HBV DNA; positive hepatitis C antibody with detectable or quantifiable HCV RNA; positive HIV antibody; positive CMV DNA; or positive syphilis antigen or antibody. * Presence of any other uncontrolled active infection. * History of major solid organ transplantation (for example, heart, lung, liver, or kidney transplantation) or bone marrow/hematopoietic stem cell transplantation. * Pregnant or breastfeeding women. * Receipt of any mRNA-LNP product or other LNP-based drug within the past 2 years. * History, within 6 months before screening, of any of the following cardiovascular conditions: NYHA Class III or IV heart failure, myocardial infarction, unstable angina, uncontrolled or symptomatic atrial arrhythmia, ventricular arrhythmia, or other clinically significant cardiac disease. * Receipt of a live vaccine within 30 days before screening. * History of asthma or severe allergy, if considered clinically significant by the investigator. * Any condition that, in the investigator's opinion, would increase risk to the participant or interfere with study assessments.
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 |
|---|---|---|
| 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. |
| Change from baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | 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 Patient Global Assessment （PtGA） | 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. |
| in vivo CAR T cell production | Up to14 days | Assessment of in vivo CAR-T cell production, defined by the proportion of CAR-expressing T cells in peripheral blood as measured by flow cytometry. |
| B-cell proportion and absolute count in peripheral blood | Up to 12 months | Assessment of peripheral blood B-cell proportion, absolute B-cell count (cells/μL), and B-cell subsets, including naive B cells and memory B cells, by flow cytometry. |
| Change from baseline in SLEDAI-2K score | Up to 12 months | Assessment of change from baseline in the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). Total scores range from 0 to 105, with higher scores indicating greater disease activity. |
| Change from baseline in Physician Global Assessment (PGA) | Up to 12 months | Assessment of change from baseline in Physician Global Assessment (PGA) at scheduled visits through Month 12. Scores range from 0.0 to 3.0, with higher scores indicating greater disease activity. |
| Proportion of participants achieving lupus low disease activity status (LLDAS) | Up to 12 months | Proportion of participants who achieve LLDAS at scheduled visits through Month 12 |
| Proportion of patients achieving DORIS remission | Up to 12 months | Proportion of participants who achieve Definitions of Remission in SLE (DORIS) remission at scheduled visits through Month 12. |
| Change from baseline in British Isles Lupus Assessment Group 2004 (BILAG-2004) index | Up to 12 months | Assessment of change from baseline in the BILAG-2004 index. The BILAG-2004 index evaluates 97 clinical manifestations of SLE across 9 organ domains, with activity in each domain graded from A to E, the activity level of the disease respond to the score. |
| Proportion of participants achieving SRI-4 response | Up to 12 months | Proportion of participants who meet the criteria for the Systemic Lupus Erythematosus Responder Index-4 (SRI-4) at scheduled visits through Month 12. |
Countries
China
Contacts
CONTACTZhu Chen
CONTACTZexiu Xiao
PRINCIPAL_INVESTIGATORZhu Chen
The First Affiliated Hospital of University of Science and Technology of China
Outcome results
None listed