The Safety, Tolerability, Pharmacokinetics, Immunogenicity and Preliminary Efficacy of HC022 Injection in Subjects With SLE/CLE

A Multicenter, Randomized, Double-blind, Placebo-controlled Phase Ib Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity Characteristics and Preliminary Efficacy of Multiple Ascending Doses of HC022 Injection in Subjects With Systemic Lupus Erythematosus and/or Cutaneous Lupus Erythematosus

The primary objective of this phase Ib study is to evaluate the safety and tolerability of multiple-ascending, subcutaneous (SC) doses of HC022 in SLE/CLE subjects. Secondary objectives of study are as follows: To estimate the PK parameters of multiple-ascending SC doses of HC022 in SLE/CLE subjects；To evaluate the immunogenicity of HC022 administered to SLE/CLE subjects.

Inclusion Criteria:

• 1. Subjects who voluntarily participate in the study, are able to sign the informed consent form and comply with the requirements on the informed consent form;
• 2. Age ≥ 18 years, regardless of gender;
• 3. Subjects and their partners have no birth plan during the study treatment period and within 6 months after the last dose, and voluntarily use effective and reliable contraception (Attachment 1). Female subjects must have a negative serum pregnancy test and be non-lactating;
• 4. Patients diagnosed with SLE or CLE by the investigator

Exclusion Criteria:

• 1. active severe lupus nephritis
• 2. active neuropsychiatric SLE
• 3 .History or current diagnosis of any other systemic autoimmune disease other than secondary Sjogren's syndrome, including but not limited to rheumatoid arthritis, psoriatic arthritis, dermatomyositis, systemic sclerosis (scleroderma), clinically significant non-SLE related vasculitis;
• 4. Drug-induced lupus;
• 5. HIV medical history or positive test results, treponema pallidum antibody positive, hepatitis B infection (HBsAg or HBcAb positive), hepatitis C infection (HCV antibody positive and quantitative abnormality), cytomegalovirus infection (IgM positive and quantitative abnormality) and Epstein-Barr virus infection (IgM positive and quantitative abnormality);
• 6.History of tuberculosis infection, or evidence of active or latent mycobacterium tuberculosis infection at the time of signing informed consent;
• 7. The following laboratory abnormalities were present, including but not limited to: a) Subjects with abnormal liver function: e.g., aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2 times the upper limit of normal (ULN), or total bilirubin > 1.5 × ULN (except for those due to Gilbert syndrome); or b) Subjects with abnormal hematology: Hemoglobin < 90 g/L, or platelet count < 75 x 109/L, or absolute neutrophil count < 1.5 x 109/L;
• 8. Subjects with a history of chronic, recurrent (3 or more infections of the same type within 1 year) or severe infections (e.g. pneumonia and sepsis) within half a year before informed consent as determined by the investigator, including viral infection, or requiring systemic anti-infective treatment within 12 weeks before informed consent;
• 9.History of severe herpes infection (e.g., herpetic encephalitis, ocular herpes or diffuse herpes) or signs of herpes or varicella-zoster virus infection within 12 weeks prior to knowledge (especially chickenpox and herpes zoster);
• 10. History or current history of malignant disease, including solid tumors and hematologic malignancies (except for basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and cervical cancer in situ that have been completely removed and considered cured > 2 years at the time of informed consent).
• 11. New York Heart Association Functional Class III or IV congestive heart failure
• 12. Subjects with informed consent or abnormal and clinically significant ECG results before administration
• 13.Patients with suicidal behavior or thoughts within 1 year before informed consent;
• 14.Subjects with a history of drug abuse within 12 months before informed consent, or positive baseline urine drug test results;
• 15. Use the prohibited drugs stipulated in the plan
• 16. Antimalarials were started within 12 weeks prior to randomization, and subjects must have been on a stable dose from screening through the end of study (only for CLE patients) if they were receiving antimalarial treatment at screening;
• 17. Treatment with oral systemic corticosteroids at doses greater than 15 mg/day prednisone (or its equivalent) prior to randomization (only for patients with CLE);
• 18. Patients who have previously received drugs that inhibit BDCA2 targets;
• 19. Subjects who have participated in other clinical trials within 4 weeks before informed consent, or within 5 half-lives of the investigational drug, whichever is longer;
• 20. Presence of a past or present condition other than SLE and/or CLE that, in the opinion of the Investigator, may interfere with the assessment of skin inflammation and disease activity;
• 21. Subjects who are allergic to the investigational drug (including excipients) or suffer from serious allergic diseases or have an allergic constitution (such as allergy to two or more drugs, food or pollen), which may impair the safety of subjects in the judgment of the investigator;
• 22. Tattoos, scars or other physical examination findings in the area of planned injection sites that interfere with local injection site evaluation;
• 23. Live vaccine or live attenuated vaccine within 4 weeks before informed consent, or planned during the study and within 24 weeks after the last dose of study drug;
• 24. Subjects with a blood donation volume ≥ 500 mL within 4 weeks before informed consent or planned during the study, or have a history of blood transfusion within 4 weeks before informed consent;
• 25. Subjects with an average daily alcohol intake of more than 2 units (1 unit of alcohol ≈ 360 mL of beer containing 5% alcohol or 45 mL of spirits containing 40% alcohol or 150 mL of wine containing 12% alcohol) within 3 months before informed consent, or subjects with positive baseline alcohol breath test;
• 26. Other reasons that the investigator considers unsuitable for participation in this study.