A Study to Evaluate the Safety and Pharmacokinetics With MEDI8367 Administered in Healthy Subjects, and in Subjects With Chronic Kidney Disease
Condition: Chronic Kidney Disease
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic
Study type: Interventional
Phase: Phase 1

Summary: 
      This Phase I First in Human (FIH) study is being conducted to determine the safety,
      pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity profile of MEDI8367 across
      the dose range.
    

Detailed description: 
      This is a Phase I, FIH, randomized, blinded, placebo-controlled study, to evaluate the safety
      and PK of MEDI8367 as single ascending doses (SAD) in healthy subjects and as a single dose
      in healthy subjects of Japanese-descent and in subjects with chronic kidney disease (CKD).

      Six cohorts, Cohorts 1 to 5 (healthy volunteers including Japanese subjects in Cohort 5) each
      consisting of 8 subjects (total 40 subjects), and Cohort 6 (subjects with CKD) consisting of
      30 subjects, will participate in the study. The starting dose is dose A of MEDI8367 with up
      to 3 dose escalations planned (provisional doses of dose B, dose C, and dose D).

      The study will comprise of:

        -  A Screening Period of maximum 28 days;

        -  A Treatment Period during which subjects will be resident at the Clinical
           Unit/non-clinical sites from the day before investigational medicinal product (IMP)
           administration (Day -1) until at least 72 hours after IMP administration; discharged on
           Day 4; and

        -  A Follow-up Period (out-patient) with 8 visits; the final Follow-up Visit (Visit 10)
           within 90 ± 4 days after the last IMP dose. The study day for the last visit may be
           adjusted based on PK/PD results from the current and previous cohorts.

      Dosing for Cohorts 1 to 4 and Cohort 6 will proceed with 2 subjects in a sentinel cohort,
      such that one subject will be randomized to receive MEDI8367 and one subject will be
      randomized to receive placebo. The blinded safety data from the sentinel subjects up to 3
      days post-dose will be reviewed by the site Principal Investigator (PI) before the remaining
      subjects in the cohort are dosed. Dosing is proposed to continue based on a lack of
      significant safety findings in the first 2 subjects dosed per cohort. The remaining 6
      subjects in Cohorts 1 to 4, respectively, and 28 subjects in Cohort 6, will be dosed at least
      3 days after the sentinel cohort.
    

Intervention name(s): MEDI8367; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Subjects will receive subcutaneous (SC) single dose of MEDI8367, depending upon dose escalation strategy and Safety Review Committee results. The maximum dose will not exceed 600 mg. The dose will be administered as a single injection or multiple injections in the abdomen region.; Saline solution for injection and the placebo volume to be administered will be equivalent to the MEDI8367 volume administered for each dosing cohort.
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: First-in-human, Single Ascending Dose