| Eligibility |
Inclusion Criteria (subjects must meet all the following criteria for inclusion in this
study):
Single Dose:
1. Male or female, 18-65 years old (inclusive), weight of = 45 kg.
2. Definite diagnosis of systemic lupus erythematosus (see Annex 3. SLE Classification
Criteria by SLICC 2012 for diagnostic criteria), and an SLE disease activity index
(SLEDAI) score of < 15 (see Annex 4. SLE Disease Activity Score [SLEDAI-2000] for
scoring criteria) . A positive antinucleus antibody (ANA) test result.
3. If a subject is receiving SLE treatment, a stable SLE regimen must be maintained up to
the date of the first dose of study drug (the permitted medications and their maximum
doses are as follows):
- Glucocorticoids: prednisone 10 mg/day or other glucocorticoids with an equivalent
dose. It should be stable for at least 4 weeks prior to receiving the first dose
of study drug.
- Other immunosuppressive drugs alone or in combination with glucocorticoids
include the following: azathioprine (maximum dose of 100 mg/day), methotrexate
(maximum dose of 15 mg/week), mycophenolate mofetil (maximum dose of 1500
mg/day), tripterygium wilfordii polyglycosides (maximum dose of 60 mg/day),
leflunomide (maximum dose of 20 mg/day), tacrolimus (maximum dose of 4 mg/day),
ciclosporin (maximum dose of 100 mg/day). The above medications should be used
for at least 12 weeks and stable for at least 4 weeks prior to receiving the
first dose of study drug.
- Hydroxychloroquine: The maximum allowable dose is 400 mg/day, and combination
with the immunosuppressants listed above is allowed. It should be used for at
least 12 weeks and the dose should be stable for at least 4 weeks prior to
receiving the first dose of study drug.
4. The subject is willing to participate in the study and voluntarily sign the ICF.
5. Subjects of childbearing potential or subjects with a partner of childbearing
potential must agree to use effective contraceptive measures throughout the study
(except oral estrogens, estrogenic vaginal ring, etc., refer to Annex 5. Contraceptive
Measures, Definitions of Women of Childbearing Potential and Contraception
Requirements for optional contraceptive methods).
Multiple Doses: in addition to the single-dose inclusion criteria, subjects should
meet the following criteria
6. dsDNA antibody titer (ELISA) greater than or equal to 1.5 times the upper limit of
normal (ULN).
Exclusion Criteria (subjects who meet any of the following criteria will be excluded from
the study):
1. Central nervous system (CNS) diseases: active central nervous system lupus (including
epilepsy, psychosis, organic encephalopathy syndrome, cerebrovascular accident,
encephalitis, or CNS vasculitis), visual disturbance, cranial neuropathy within 60
days prior to screening, with intervention required.
2. Renal disorders: nephrotic syndrome (protein urine > 3.5 g/24 h) within 30 days prior
to screening, or requiring protocol-prohibited medications (such as intravenous
cyclophosphamide) for active nephritis, or requiring hemodialysis or high-dose
glucocorticoids such as prednisone of = 100 mg/day (or other glucocorticoids with
equivalent doses).
3. Cardiovascular disorders: history of acute myocardial infarction, or unstable angina,
severe arrhythmia (multifocal frequent ventricular premature beats, ventricular
tachycardia, ventricular fibrillation), etc. over the past six months; New York Heart
Association (NYHA) Class III-IV (see Annex 6. NYHA for details).
4. Subjects with a known history of moderate or severe persistent asthma (assessed by the
Asthma Severity Scale of the National Heart, Lung, and Blood Institute [NHLB]) within
the past 5 years, or who currently have uncontrolled asthma (of any grade).
5. Asthma and specific dermatitis, etc. requiring glucocorticoid-dependent therapy
(except topical glucocorticoids).
6. Infections, requiring treatment for acute or chronic infections, as follows:
- Treatment with any inhibitory therapy currently for chronic infections (e.g.,
tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, zoster virus
and atypical mycobacteriosis);
- Hospitalization for an infection within 60 days prior to dosing;
- Treatment with anti-infective drugs (antibacterials, antivirals, antifungals, or
antiparasites) by parenteral administration (IV or IM) 60 days prior to dosing.
- Subjects with mycobacterium tuberculosis, including those with a positive "T-cell
spot test for tuberculosis infection (T-SPOT)" (latent tuberculosis infection:
except those who have completed tuberculosis prophylaxis for 4 weeks before their
first dose), or those with a positive imaging result.
7. Subjects with positive results from any of the following tests: hepatitis B surface
antigen (HBs Ag), hepatitis B core antibody (HBc Ab), hepatitis C virus antibody (HCV
Ab), human immunodeficiency virus antibody (HIV Ab), or treponema pallidum antibody
(TPPA). Patients who tested positive for hepatitis B core antibody (HBc Ab) but
negative for HBV-DNA should be excluded.
8. Hematological system diseases or hematology abnormalities: subjects with previous or
current hematological system diseases (including but not limited to: myelofibrosis,
anemia aplastic aregenerative, leukemia, lymphoma, etc.), hematology with hemoglobin <
100 g/L, white blood cells < 3.0 × 109/L, granulocytes < 2.5 × 109/L, lymphocytes <
0.8 × 109/L, or platelets < 100 × 109/L.
9. Abnormal liver function: aspartate aminotransferase (AST) or alanine aminotransferase
(ALT) or glutamyl transpeptidase (GGT) values > 2 times ULN; or total bilirubin or
alkaline phosphatase (ALP) values > 1.5 times ULN.
10. Abnormal renal function: creatinine (Cr) or urea nitrogen (BUN) values > 1.5 times the
upper limit of normal (ULN); pre-screening estimated glomerular filtration rate (eGFR)
= 60 mL/min. Calculate eGFR values using the MDRD formula: eGFR (mL/min × 1.73 m2) =
175 × blood creatinine ([Scr (mg/dL)])-1.154 × age-0.203 × sex (M = 1, F = 0.742).
11. Cancer: history of malignancy within the last 5 years.
12. Transplant: history of major organ transplant (e.g., heart, lung, kidney, liver) or
hematopoietic stem cell or bone marrow transplant.
13. Female subjects with a positive serum pregnancy test or currently lactating.
14. History of major surgery (craniotomy, thoracotomy, or laparotomy) or presence of
unhealed wounds, ulcers, or fractures within 4 weeks prior to the first dose of study
treatment.
15. Targeted drug therapy: rituximab within 180 days before the first dose; any drug
therapy targeting T-lymphocytes, B-lymphocytes, cytokines or receptors [e.g.,
belimumab, telitacicept, abatacept, etc.] within 90 days before the first dose; JAK
inhibitors within 30 days before the first dose; other investigational drugs for less
than 5 half-lives.
16. Subjects who have participated in any other clinical trials (including receiving
investigational vaccines) or received treatment with invasive and investigational
medical devices within 3 months before inclusion, or are being enrolled into an
interventional and investigational study.
17. Stable doses of anticoagulant or antiplatelet drugs used before randomization that
exceeded regular doses or was increased within 7 days before dosing.
18. Immunosuppressants:
- Have received any of the following treatments within 90 days prior to screening:
Intravenous immunoglobulin (IVIG);Use of high-dose glucocorticoids such as
prednisone = 100 mg/day;Plasma exchange, leukopheresis;Cyclophosphamide.
- Use of immunomodulatory agents such as thymosin within 30 days prior to
screening.
19. Vaccination within 30 days prior to the first dose of study treatment.
20. Use of traditional Chinese medicinal products or herbal preparations such as total
glucosides of white paeony capsules, zhengqinfengtongning and colquhounia root tablets
within 30 days prior to the first dose of study treatment.
21. Drug abusers determined by medication history inquiries, including morphine, ketamine,
tetrahydrocannabinolate, methamphetamine, dimethyldioxymethamphetamine and cocaine.
22. Subjects who have consumed more than 14 units of alcohol/week (1 unit of alcohol = 360
mL of beer, 150 mL of wine, or 45 mL of liquor) within 3 months prior to screening, or
who cannot abstain from alcohol during the trial, as determined by history inquiries.
23. Other conditions: including laboratory abnormalities, history of any other disease
(e.g., recent history of septicemia), clinically significant unstable or uncontrolled
acute or chronic conditions unrelated to SLE (e.g., acute pneumonia, pulmonary
arterial hypertension, diabetic ketoacidosis, acute pancreatitis, etc.). In the
opinion of the investigator, the above conditions may confound the study results or
place the subject at an inappropriate risk. Thus, the subjects who experience the
conditions above are not suitable for participation in this study.
24. Subjects who are unsuitable for participation in this clinical study for any other
reasons as determined by the investigator.
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