Phase Ib Clinical Study to Evaluate the Safety and Tolerability of VSA012 Injection in Paroxysmal Nocturnal Hemoglobinuria

Inclusion and Exclusion Criteria for Groups 1-4

• Participants voluntarily participate in this clinical study, and voluntarily sign the ICF;
• BMI ≥ 18.0 kg/m2; male or female; 18 to 75 years of age;
• Confirmed diagnosis of PNH by clinical manifestation and flow cytometry; granulocyte clone size ≥ 10%;
• Presence of one or more of PNH-related signs or symptoms within 3 months prior to screening;
• Hb < 100 g/L;
• LDH value > 1.5 × ULN;
• One of the following criteria for prior drug therapy for PNH must be met:

• Having never received any complement inhibitor therapy;
• Having received C5, C3, or CFB complement inhibitors and having discontinued the complement inhibitor for more than 5 half-lives or 3 months prior to screening;
• Participants are willing to receive meningococcal vaccine and pneumococcal vaccine at least 14 days prior to dosing.

Inclusion and Exclusion Criteria for Groups 5

• Participants voluntarily participate in this clinical study, and voluntarily sign the ICF;
• BMI ≥ 18.0 kg/m2; male or female; 18 to 75 years of age;
• Confirmed diagnosis of PNH by clinical manifestation and flow cytometry; granulocyte clone size ≥ 10%;
• Participants who have been on a stable dose and interval of a C5 complement inhibitor (approved locally) for at least 3 months prior to the first dose of VSA012;
• Within the 3 months prior to screening, have a documented Hb level of < 105 g/L while on C5 complement inhibitor therapy;
• Hb < 105 g/L;
• Participants are willing to receive meningococcal vaccine and pneumococcal vaccine at least 14 days prior to dosing.

Exclusion criteria

for Groups 1-4

• History of hypersensitivity to VSA012 or its excipients;
• Use of any complement inhibitors within 3 months prior to screening
• Use of any targeted small interfering RNA (siRNA) within 18 months prior to screening, or any antisense oligonucleotide molecule within 6 months prior to screening;
• Supportive care for PNH does not meet the stable-dose requirements:
• Participants have infections;
• Laboratory tests meet the following criteria:

• Reticulocyte count < 100 × 109/L;
• Platelet count < 30 × 109/L;
• Neutrophil count < 0.5 × 109/L;
• Creatinine clearance < 30 mL/min (calculated by the Cockcroft-Gault formula);

Exclusion criteria

for Groups 5

• History of hypersensitivity to VSA012 or its excipients;
• Use of any targeted small interfering RNA (siRNA) within 18 months prior to screening, or any antisense oligonucleotide molecule within 6 months prior to screening;
• Supportive care for PNH does not meet the stable-dose requirements:
• Participants have infections;
• History of splenectomy;
• Previous suspected/confirmed hereditary complement deficiency;
• History of recurrent invasive infections with capsular bacteria, e.g., meningococcus or pneumococcus;
• Laboratory tests meet the following criteria:

• Reticulocyte count < 100 × 109/L;
• Platelet count < 30 × 109/L;
• Neutrophil count < 0.5 × 109/L;
• Creatinine clearance < 30 mL/min (calculated by the Cockcroft-Gault formula);