Evaluation of the Safety and Tolerability of Gemini in Subjects With Stage 3-4 Chronic Kidney Disease.

Design: Randomized, Placebo Controlled, Single Blind, Single-Ascending Dose Study in Patients with Stage 3-4 CKD.

This study is planned as a placebo controlled, single dose, escalating dose study to evaluate the safety and tolerability of intravenous Gemini in adult subjects with stage 3 or 4 chronic kidney disease. This study will enroll up to 40 subjects in up to 5 cohorts. Each cohort will consist of 8 unique subjects, 6 assigned to Gemini and 2 assigned to placebo. All subjects will provide written informed consent and be screened for eligibility before enrollment. All eligibility criteria must be met prior to dosing.

On Day 1, each study subject will receive a single IV dose (each total dose volume = 20 mL) via syringe pump for at least 10 minutes but not longer than 15 minutes and as per the institution's standard method. Time 0 starts once the entire dose is administered and the line has been flushed to ensure any residual drug is delivered.

A Safety Review Committee (SRC) will assess safety and tolerability including AEs, after at least 6 subjects in each cohort have completed Day 8 to determine the subsequent cohort dose. If a grade 3 or higher adverse event is not experienced, as determined by the SRC, or the criteria for stopping dosing has not been met at a given cohort dose level, dose escalation will proceed to the next cohort and dose level.

Dosing will continue until any cohort experiences a dose limiting toxicity (DLT), defined as a dose that causes any grade 3 or higher adverse event, or stopping criteria is met or the highest dose as determined in the Phase 1 study has been tolerated. If a dose is stopped due to a DLT or stopping criteria, cohorts scheduled at a higher dose will not be utilized. The SRC will meet to review safety and tolerability data and may determine if a lower dose can be given. This dose will be documented in the minutes and a dose recommendation memo which will be provided to the clinical sites.

Once the maximum tolerated dose is determined, the dose will be repeated (Cohort 4) for a total of 16 subjects dosed at the highest level tolerated. The repeated dose cohort will consist of 8 unique subjects, 6 assigned to Gemini and 2 assigned to placebo. If the maximum tolerated dose is reached within the first 2 cohorts, the dose will be repeated until a minimum of 32 subjects are enrolled.

If the highest dose determined in the Phase 1 study is tolerated, optional higher dosing of may be administered as determined by the SRC, or the same dose will be repeated.