Phase 1 Study to Assess AER-271
Condition: Stroke; Stroke, Acute; Stroke, Ischemic
MeSH terms: Stroke; Ischemic Stroke
Study type: Interventional
Phase: Phase 1

Summary: 
      The objective of this Phase 1 trial is to assess the safety, tolerability and
      pharmacokinetics of AER-271 in health subjects.
    

Detailed description: 
      This is a double-blind, randomized, placebo-controlled, sequential-group study to assess the
      safety, tolerability and pharmacokinetics of single ascending dose and multiple ascending
      doses of intravenously (IV) administered AER-271 in healthy human subjects. AER-271 is an
      Aquaporin-4 inhibitor designed to prevent brain swelling in severe ischemic stroke. The study
      will be conducted in 2 parts: Part A is a single ascending dose, sequential group study. The
      subsequent Part B is a multiple ascending dose, sequential group study. Both Parts A and B
      will follow an adaptive design including the use of Sentinel Dosing.

      The primary objectives of this study are to assess the safety and tolerability of single and
      multiple IV doses and continuous infusion of AER-271 in healthy subjects. Secondary
      objectives include: determining the pharmacokinetics of AER-271 and AER-270 following
      administration of AER-271, determining the dose proportionality for AER-270 and 271, and
      comparing the effects of continuous infusion versus multiple bolus doses on AER-271 exposure
      and adverse events. An additional exploratory objective of this study is to evaluate the
      effects of AER-271 on electrocardiogram parameters including QT interval corrected for heart
      rate. Data from this trial will also be used to develop a protocol for a subsequent Phase 2
      clinical trial in stroke patients.
    

Intervention name(s): AER-271; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): AER-271, the test article for this study.; Placebo control for this study.
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention model description: A double-blind, randomized, placebo-controlled, sequential-group, single and multiple intravenous dose escalation study conducted in 2 parts. Both Parts A and B will comprise an adaptive design. Part A sentinel dosing will randomize the first 2 subjects 1:1 AER-271:placebo. The remaining 6 subjects in a cohort will be randomized 5:1 AER-271:placebo and administered drug after the Safety Monitoring Board (SMB) has reviewed the first 24 hours of safety data for the first 2 subjects. Part B sentinel dosing will randomize the first 4 subjects 2:2 AER-271:placebo. The remaining 6 subjects in a cohort will be randomized 4:2 AER-271:placebo and administered study drug after the SMB has reviewed the first 24 hours of safety data for the first 4 subjects. Part A will have 6 cohorts and Part B will have 3. Additional cohorts may be enrolled to explore additional dose levels. The planned study design may be modified in accordance with the adaptive features of the clinical study protocol.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: stroke; acute ischemic stroke; cerebral edema