Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Intravenous Secukinumab in Patients With GCA or PMR

Exclusion Criteria

• •1. Pregnant or nursing (lactating) women where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test
• •2. History of hypersensitivity or contraindication to any of the study treatments or its excipients or to drugs of similar chemical classes
• •3. Use of other investigational drugs within 5 half-lives of enrollment or within 30 days (e.g., small molecules) or until the expected pharmacodynamic effect has returned to BSL (e.g., biologics), whichever is longer; or longer if required by local regulations
• •4. History of clinically significant liver disease or liver injury as indicated by clinically significantly abnormal liver function tests (LFTs), such as SGOT (AST), SGPT (ALT) and serum bilirubin. The Investigator should be guided by the following criteria:
• •* AST (Aspartate Aminotransferase) and ALT (Alanine Aminotransferase) may not exceed 3 x the upper limit of normal (ULN)
• •* Total bilirubin concentration may not exceed 1.5 x ULN Any one of these parameters, if elevated above ULN, should be re-checked once more as soon as possible, and in all cases, at least prior to enrollment, to rule-out laboratory error.
• •5. Active infections or history of ongoing, chronic or recurrent infectious disease including but not limited to below:
• •* Active infections during the last 2 weeks prior to BSL
• •* Known infection with human immunodeficiency virus (HIV), hepatitis B (HBV) or hepatitis C (HCV) at screening or BSL, except for HCV successfully treated and cured, according to local/global guidelines
• •* Evidence of tuberculosis (TB) infection as defined by a positive QuantiFERON TB-Gold Plus test. Participants with a positive test may participate in the study if further work-up (according to local practice/guidelines) establishes conclusively that the participant has no evidence of active TB. If the test result is indeterminate, the Investigator may repeat the test once or may proceed directly to perform the work-up for TB as per local procedures. If presence of latent TB is established, then treatment must be initiated prior to BSL (both treatment and timing prior to BSL according to local country guidelines)
• •6. Active inflammatory bowel disease or active uveitis
• •7. Active ongoing diseases which in the opinion of the Investigator immuno-compromises the participant and/or places the participant at unacceptable risk for treatment with immunomodulatory therapy
• •8. Current severe progressive or uncontrolled disease, which in the judgment of the Investigator renders the participant unsuitable for the trial, including but not limited to below:
• •* Major ischemic event (e.g., myocardial infarction, stroke, etc.) or transient ischemic attack (TIA) within 12 weeks of screening
• •* Significant medical conditions or diseases, including but not limited to the following: uncontrolled hypertension, congestive heart failure (New York Heart Association (NYHA) status of class III or IV) and uncontrolled diabetes mellitus
• •* Any other current severe progressive or uncontrolled diseases per the Investigator's discretion
• •9. Confirmed diagnosis of any primary form of systemic vasculitis, other than GCA
• •1. Pregnant or nursing (lactating) women where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test
• •2. History of hypersensitivity or contraindication to any of the study treatments or its excipients or to drugs of similar chemical classes
• •3. Use of other investigational drugs within 5 half-lives of enrollment or within 30 days (e.g., small molecules) or until the expected pharmacodynamic effect has returned to BSL (e.g., biologics), whichever is longer; or longer if required by local regulations
• •4. History of clinically significant liver disease or liver injury as indicated by clinically significantly abnormal liver function tests (LFTs), such as SGOT (AST), SGPT (ALT) and serum bilirubin. The Investigator should be guided by the following criteria:
• •* AST (Aspartate Aminotransferase) and ALT (Alanine Aminotransferase) may not exceed 3 x the upper limit of normal (ULN)
• •* Total bilirubin concentration may not exceed 1.5 x ULN Any one of these parameters, if elevated above ULN, should be re-checked once more as soon as possible, and in all cases, at least prior to enrollment, to rule-out laboratory error.
• •5. Active infections or history of ongoing, chronic or recurrent infectious disease including but not limited to below:
• •* Active infections during the last 2 weeks prior to BSL
• •* Known infection with human immunodeficiency virus (HIV), hepatitis B (HBV) or hepatitis C (HCV) at screening or BSL, except for HCV successfully treated and cured, according to local/global guidelines
• •* Evidence of TB infection as defined by a positive QuantiFERON TB-Gold Plus test. Participants with a positive test may participate in the study if further work-up (according to local practice/guidelines) establishes conclusively that the participant has no evidence of active TB. If the test result is indeterminate, the Investigator may repeat the test once or may proceed directly to perform the work-up for TB as per local procedures. If presence of latent TB is established, then treatment must be initiated prior to BSL (both treatment and timing prior to BSL according to local country guidelines)
• •6. Active inflammatory bowel disease or active uveitis
• •7. Active ongoing diseases which in the opinion of the Investigator immuno-compromises the participant and/or places the participant at unacceptable risk for treatment with immunomodulatory therapy
• •8. Current severe progressive or uncontrolled disease, which in the judgment of the Investigator renders the participant unsuitable for the trial, including but not limited to below:
• •* Major ischemic event (e.g., myocardial infarction, stroke, etc.) or transient ischemic attack (TIA) within 12 weeks of screening
• •* Significant medical conditions or diseases, including but not limited to the following: uncontrolled hypertension, congestive heart failure (New York Heart Association (NYHA) status of class III or IV) and uncontrolled diabetes mellitus
• •* Any other current severe progressive or uncontrolled diseases per the Investigator's discretion
• •9. Evidence of GCA as indicated by typical (cranial) symptoms (e.g., persistent or recurrent localized headache, temporal artery or scalp tenderness, jaw claudication, blurry or loss of vision, symptoms of stroke), extremity claudication, imaging and/or temporal artery biopsy result
• •• Note: Imaging and/or temporal artery biopsy are not standard of care for PMR management and diagnosis and are therefore not mandated as part of the screening; Patients with PMR symptoms only who have a temporal artery biopsy in line with GCA and/or radiologic signs of vasculitis may be eligible for the GCA cohort
• •10. Concurrent rheumatoid arthritis or other inflammatory arthritis or other connective tissue diseases, such as but not limited to systemic lupus erythematosus, systemic sclerosis, vasculitis, myositis, mixed connective tissue disease, and ankylosing spondylitis
• •11. Concurrent diagnosis or history of neuropathic muscular diseases including fibromyalgia
• •12. Inadequately treated hypothyroidism (e.g., persistence of symptoms, lack of normalization of serum TSH despite regular hormonal replacement treatment)