Systemic lupus erythematosus (SLE) Skin and Connective Tissue Diseases
Conditions
Interventions
After meeting the eligibility criteria, all eligible participants will be randomized 1:1:1:1:1:1 to a device group (APFS or AI) for an anatomical injection site as defined in the protocol. Randomizati
Sponsors
AstraZeneca (United States)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Healthy male and female subjects (childbearing and non-childbearing potential) aged 18 – 55 years (inclusive) at Screening with suitable veins for cannulation or repeated venipuncture at screening. 2. Female subjects of childbearing potential must have a negative pregnancy test at Screening. 3. Female subjects of childbearing and non-childbearing potential and male subjects must adhere to the contraception methods. 4. Have a body mass index between 18.5 and 30 kg/m² inclusive and weigh at least 50 kg and no more than 110 kg inclusive at Screening. 5. Subjects must have immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), either by having recovered from a SARS-CoV-2 infection (should have recovered from infection at least 6 weeks before Screening Visit as confirmed by a COVID-19 test) or fully vaccinated against SARS CoV-2 with vaccines approved in the local region (should have received the final vaccine dose at least 2 weeks before Screening Visit). 6. Subject should meet all of following tuberculosis (TB) criteria: 6.1. No signs or symptoms of active TB prior to or during any Screening visit. 6.2. No medical history or past physical examinations suggestive of active TB. 6.3. No recent contact with a person with active TB OR if there has been such contact, referral to a physician specializing in TB to undergo additional evaluation prior to randomization (documented comprehensively in source), and, if warranted, receipt of appropriate treatment for latent TB at or before the first administration of IP. 6.4. No history of latent TB prior to initial Screening visit, with the exception of latent TB with documented completion of appropriate treatment. 7. Negative result for an Interferon-gamma (IFN-?) release assay (IGRA) (eg QuantiFERON-TB Gold [QFT-G] test) test for TB at screening.
Exclusion criteria
Exclusion criteria: 1. Lactating or pregnant females or females who intend to become pregnant or begin breastfeeding anytime from initiation of Screening until 1 month after the final Follow-up Visit. 2. History or presence of hepatic or renal diseases known to interfere with the PK of anifrolumab. 3. Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the administration of SI, as judged by the Investigator. 4. Any clinically significant abnormalities in in clinical chemistry, hematology, or urinalysis results, at Screening and/or admission to the Clinical Unit. 5. Any clinically significant abnormal findings in vital signs at Screening and/or admission to the Clinical Unit. 6. Any clinically significant abnormalities on 12-lead electrocardiogram at Screening and/or admission to the Clinical Unit, as judged by the Investigator. 7. Any positive result on Screening for serum hepatitis B surface antigen OR anti-HBc antibody, hepatitis C antibody, and HIV antibody. 8. Opportunistic infection requiring hospitalization or IV antimicrobial treatment within 3 years of randomization. 9. Clinically significant chronic infection (eg, osteomyelitis, bronchiectasis, etc.) within 8 weeks prior to signing the informed consent form (ICF). 10. Any infection requiring hospitalization or treatment with IV anti-infective medications not completed at least 4 weeks prior to signing the ICF. 11. Any infection requiring oral anti-infective medications (including antivirals) within 2 weeks prior to Day 1 12. History of severe Coronavirus Disease 2019 (COVID-19) infection requiring hospitalization within the last 12 months prior to Screening, or clinical history compatible with Long COVID 19 (symptoms beyond 12 weeks of acute infection), as judged by the Investigator 13. COVID-19 infection before or during Screening and/or admission confirmed by a COVID 19 test (in the London Clinical Unit, subjects will undergo COVID-19 testing prior to ICF signing and any subject testing positive will not be screened for the study). 14. Known or suspected history of drug abuse, as judged by the Investigator. 15. Positive screen for drugs of abuse or cotinine at Screening or on admission to the Clinical Unit or positive screen for alcohol at Screening or on admission to the Clinical Unit. 16. Participation in another clinical trial, or has received another new chemical entity (defined as a compound which has not been approved for marketing) within 3 months of the administration of SI in this study. The period of exclusion begins 3 months after the final dose or 5 half-lives, whichever is the longest. 17. Plasma donation within 1 month of Screening or any blood donation/loss more than 500 mL during the 3 months prior to Screening. 18. A known history of allergy or reaction to any component of the IP formulation or history of anaphylaxis to any human gamma globulin therapy. 19. Current smokers or those who have smoked or used nicotine products (including e-cigarettes) within the 3 months prior to Screening. 20. Use of drugs with enzyme-inducing properties such as St John’s Wort within 3 weeks prior to the administration of SI. 21
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Measured using blood test from Day 1 to Day 57 1. Area under serum concentration-time curve from time zero extrapolated to infinity (AUCinf). 2. Area under serum concentration-time curve from time zero to last quantifiable concentration (AUClast). 3. Maximum observed serum (peak) drug concentration (Cmax). | — |
Secondary
| Measure | Time frame |
|---|---|
| Measured using blood test from Day 1 to Day 57 1. Time to reach peak or maximum observed concentration (tmax). 2. Half-life associated with terminal slope (?z) of a semi-logarithmic concentration-time curve (t1/2?z). 3. Mean residence time of the unchanged drug in the systemic circulation from zero to infinity (MRT). 4. Apparent total body clearance of drug after extravascular administration (CL/F). 5. Apparent volume of distribution following extravascular administration (based on terminal phase) (Vz/F). 6. Time of last quantifiable concentration (tlast). Measured at screening period (Day -28 to Day-2) through follow-up visit (Day 57) 7. Adverse Events, Injection site pain and pruritis assessed using visual analog scale 100 mm, Injection site erythema, induration and swelling assessed using the injection site reaction score, Vital signs (systolic and diastolic blood pressure, pulse and body temperature), 12-lead Electrocardiogram, Physical examination, Laboratory assessments (hematology, clinical chemistry, and urinalysis). 8. Anti-drug antibodies (ADA) measured using ... at Day 1, 29 and 57 | — |
Countries
Germany, United Kingdom, United States of America
Outcome results
None listed