Study to Assess Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of Crovalimab in Healthy Volunteers and Participants With Paroxysmal Nocturnal Hemoglobinuria

Exclusion Criteria

• •Part 1 (HVs only):
• •Any clinically relevant history or the presence of moderate to severe respiratory, renal, hepatic, gastrointestinal, hematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, or connective tissue disease
• •Any major illness within 1 month before the screening
• •Prior splenectomy
• •History of clinically significant hypersensitivity (example: drugs, excipients) or allergic reactions
• •History or presence of clinically significant electrocardiogram (ECG) abnormalities or cardiovascular disease
• •Any contra-indication for receiving Neisseria meningitides vaccination and antibiotic prophylaxis therapy as required in the study
• •Congenital or acquired complement deficiency
• •Carriers of Neisseria meningitides based on cultures from nasopharyngeal swabs
• •Known active viral, bacterial or fungal infection including herpes, herpes zoster or cold sores, during the last 14 days prior to first study drug administration
• •Signs of parasitic infection (example: eosinophilia, diarrhea)
• •History of significant recurrent infections in the opinion of the investigator
• •Parts 2, 3 and 4 - PNH participants only:
• •Evidence of moderate to severe concurrent renal, liver, cardiac, pulmonary or gastrointestinal disease not related to PNH as determined by the investigator
• •History of an illness that, in the opinion of the study investigator, might confound the results of the study or that poses an additional risk to the participant by his or her participation in the study
• •History of bone marrow transplantation
• •Treatment with azathioprine or erythrocyte-stimulating agents within 14 days prior to first study drug administration
• •Splenectomy \<1 year before start of crovalimab.
• •Part 3 and 4 - PNH patients only:
• •Any evidence of sero-positive auto-immune connective tissue diseases (such as systemic lupus erythematosus, or rheumatoid arthritis)
• •Any evidence of active inflammatory conditions (including inflammatory bowel disease, or cryoglobulinemia)
• •All Parts:
• •Under active therapy with intravenous immunoglobulin (IVIG)
• •Mentally incapacitated or history of a clinically significant psychiatric disorder over the previous 5 years
• •Known or suspected hereditary complement deficiency
• •History of meningococcal meningitis
• •History of allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies or known hypersensitivity to any constituent of the product
• •Any major episode of infection requiring hospitalization or treatment with intravenous (IV) antibiotics within 28 days prior to screening or oral antibiotics within 2 weeks prior to screening and up to first study drug administration
• •History of or currently active primary or secondary immunodeficiency, including known history of human immunodeficiency virus (HIV) infection
• •Evidence of chronic active hepatitis C infection
• •Evidence of malignant disease including myelodysplastic syndrome, or malignancies diagnosed within the previous 5 years
• •Pregnant or breastfeeding, or intending to become pregnant during the study, including the OLE period, within 46 weeks (approximately 10.5 months) after the final dose of crovalimab