Study of Safety and Efficacy of HS-10542 in Patients With Paroxysmal Nocturnal Hemoglobinuria

Prior treatment

• There is or is suspected of systemic active bacteria, virus or fungal infection 2 weeks before the first administration of HS-10542 (according to the researcher's judgment)
• Major surgery within 3 months prior to the first dose. \*Note: See Appendix for definitions of Grade 3/4 surgeries.
• Except for C5 complement inhibitors (including but not limited to ecucizumab and covalizumab), the situation of participating in other clinical trials or using other study drugs or approved therapies for experimental use before screening, and the trial drug is still within 5 half-lives or 2 weeks
• Participants who have previously received B-factor inhibitor treatment, with a treatment duration of no more than one week and having stopped taking the drug for more than five half-lives before screening, may not be excluded

Other illness

• History of infection with pod bacteria (such as Neisseris meningitis, Streptococcus pneumoniae, etc.)
• Presence of a bone marrow failure disorder (e.g., aplastic anemia, myelodysplastic syndrome, myelofibrosis)
• During screening, there are advanced heart disease (such as NYHA level IV),
• unstable thrombosis events that may exist for other causes,
• Known active infection requiring systemic therapy
• Diagnosed malignant tumors in the past 5 years
• Those who have a history of splenectomy or History of bone marrow/hematopoietic stem cells or solid organ transplantation
• Severe or poorly controlled hypertension
• poorly controlled diabetes
• Those who are suspected of being allergic to experimental drugs or any ingredient in experimental drugs

Lab values

• Patients with laboratory evidence of bone marrow failure (reticulocytes \<100x109/L; platelets \<30x109/L; neutrophils \<0.5x109/L);
• Abnormal ECG: The absolute value of QTcF (QT interval corrected by Fridericia 's formula \> 450 msec for males and \> 470 msec for females; or other clinically significant abnormalities as judged by the investigator.
• Use any of the following drugs, unless there is a stable treatment plan before screening: a) erythropoietin (ESA), hypoxic-inducing factor proaminoyl hydroxylase inhibitor (HIF-PHI) or immunosuppressant for at least 8 weeks b) Systemic use of glucocorticoids (≤15 mg/day Prednisone or equivalent doses of glucocorticoids) at least 4 weeks c) Vitamin K antagonists (such as warfarin) have a stable international standardized ratio (INR) at least 4 weeks d) Low molecular weight heparin, oral anticoagulants such as aspirin, rvaroxaban, apifloxaban, etc. at least 4 weeks e) Iron supplements , vitamin B12, folic acid or androgen for at least 4 weeks
• During screening, there are serious concurrent diseases, such as severe kidney disease (such as eGFR\<30 mL/min/1.73 m2, dialysis),
• ALT/ALP\>3×ULN,

Other

• Known or suspected hereditary or acquired complement deficiency
• Currently active primary or secondary immunodeficiency
• Presence of active anemia unrelated to PNH, such as renal anemia or anemia due to blood loss.
• Screening positive blood pregnancy test and breastfeeding women at the time of the visit,

• Men or women aged more than or equal to (≥) 18 years, and less than (≤) 75 years.
• It was confirmed to be PNH during screening, and the clone size of red blood cells or/and granulocytes or/and monocytes was detected by flow cytopy ≥10%
• Stable use of C5 complement inhibitor ikuzumab/covalimab for the first 6 months of random treatment
• Have at least one blood transfusion record within the last 4 months, or sustain a hemoglobin level below 100g/L the last 4 months prior to screening.
• The average hemoglobin level from two tests conducted by the laboratory at the time of screening is less than 100 g/L, or hemoglobin level \<100g/L before transfusion.
• LDH \> 1.5 x Upper Limit of Normal (ULN) at the time of screening
• Inoccution of Neisseris meningitis and Streptococcus pneumoniae vaccine at least 2 weeks before the first administration of HS-10542;
• if HS-10542 treatment must begin less than 2 weeks after vaccination, preventive antibiotic treatment must begin at least 2 weeks after vaccination.
• Male and female subjects with fertility must agree to adopt efficient contraceptive measures with their partners within 60/120 days from the signing of the informed consent form to the last administration,
• Male subjects who are infertile (such as those who have undergone effective sterilization surgery) must take additional efficient contraceptive measures when it is uncertain whether they have sperm，