A Multicenter, Open-label, Multiple Ascending Dose Phase 1b/2 Trial to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics and Pharmacodynamics of CAN106 Intravenously in Subjects With PNH Naïve to Complement-Inhibitor Treatment
The purpose of the study is to evaluate the safety, tolerability, efficacy, pharmacokinetics, and pharmacodynamics of CAN106 administered intravenously to subjects with PNH who have not previously been treated with a complement inhibitor.
• Male or female patients ≥18 years of age.
• Body weight ≥40 kg at screening.
• Documented diagnosis of PNH within 6 months prior to screening, confirmed by high-sensitivity flow cytometry evaluation of red blood cells (RBCs), with granulocyte or monocyte clone size of ≥10%.
• LDH level ≥ 1.5 X ULN at screening.
• Mean hemoglobin(Hb)\<10 g/dL for those who have not received blood. transfusion at screening, based on 2 measurements from separate blood samples collected at interval of 2-8 weeks apart prior to the first dosing. Or hemoglobin \< 10 g/dL at the first screening and then with subsequent red blood cell transfusions.
• Presence of 1 or more of the following PNH-related signs or symptoms within 3 months of Screening: fatigue, hemoglobinuria, abdominal pain, shortness of breath (dyspnea), anemia (hemoglobin \< 10 g/dL), history of a major adverse vascular event (including thrombosis), dysphagia, or erectile dysfunction; or history of pRBC transfusion due to PNH.
• All patients must be vaccinated against meningococcal infections within 3 years prior to, or at the time of, initiating study drug. Patients who initiate study drug treatment less than 2 weeks after receiving a meningococcal vaccine must receive treatment with appropriate prophylactic antibiotics until 2 weeks after vaccination.
• If available, Haemophilus influenzae type b and Streptococcus pneumoniae vaccines can be administered according to national vaccine guidelines, and antibiotic prophylaxis should be given until 2 weeks after vaccination if the vaccines are administered within 14 days prior to administration.
• All females of childbearing potential and all males must be willing to use at least one highly effective method of contraception from signing of informed consent until 8 months after the last dose of CAN106 Injection; Male subjects with female partners of childbearing potential must be willing to use condoms in addition to using a highly effective method of contraception.
⁃ Subjects should be willing to sign the informed consent forms and comply with the study visit.