Phase 1 Study to Assess AER-271

NCT03804476 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 174273
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Stroke; Stroke, Acute; Stroke, Ischemic

Keywords

stroke; acute ischemic stroke; cerebral edema

Outcome Measures

Primary Outcomes (19)

• Number of patients that experience adverse events

  Observation for signs and symptoms of adverse events

  Changes from baseline through day 5-7 for Part A and day 15-17 Part B.

• Number of patients that experience serious adverse events

  Observation for signs and symptoms of serious adverse events

  Changes from baseline through day 5-7 for Part A and day 15-17 Part B.

• Number of patients with significant changes in ALT levels

  Patients with serum Alanine Aminotransferase exceeding or below normal values will be reported with the concentration in IU/L

  Changes from baseline through day 5-7 for Part A and day 15-17 Part B.

• Number of patients with significant changes in AST levels

  Patients with serum Aspartate Aminotransferase exceeding or below normal values will be reported with the concentration in IU/L

  Changes from baseline through day 5-7 for Part A and day 15-17 Part B.

• Number of patients with significant changes in GGT levels

  Patients with serum Gamma-Glutamyl Transferase exceeding or below normal values will be reported with the concentration in IU/L

  Changes from baseline through day 5-7 for Part A and day 15-17 Part B.

• Number of patients with significant changes in WBC

  Patients with White Blood Cell Count exceeding or below normal values will be reported in count/uL

  Changes from baseline through day 5-7 for Part A and day 15-17 Part B.

• Number of patients with significant changes in RBC

  Patients with Red Blood Cell Count exceeding or below normal values will be reported in count/uL

  Changes from baseline through day 5-7 for Part A and day 15-17 Part B.

• Number of patients with significant changes in Albumin levels

  Patients with serum Albumin exceeding or below normal values will be reported with the concentration in g/dL

  Changes from baseline through day 5-7 for Part A and day 15-17 Part B.

• Number of patients with significant changes in Bilirubin levels

  Patients with Bilirubin exceeding or below normal values will be reported with the concentration in mg/dL

  Changes from baseline through day 5-7 for Part A and day 15-17 Part B.

• Number of patients with significant changes in Platelet counts

  Patients with Platelet counts exceeding or below normal values will be reported as count/uL

  Changes from baseline through day 5-7 for Part A and day 15-17 Part B.

• Number of patients with significant changes in Hematocrit

  Patients with Hematocrit exceeding or below normal values will be reported as a %

  Changes from baseline through day 5-7 for Part A and day 15-17 Part B.

• Number of patients with significant changes in Creatinine

  Patients with serum Creatinine exceeding or below normal values will be reported with the concentration in mg/dL

  Changes from baseline through day 5-7 for Part A and day 15-17 Part B.

• Number of patients with significant changes in Alkaline Phosphatase levels

  Patients with serum Alkaline Phosphatase exceeding or below normal values will be reported with the concentration in IU/L

  Changes from baseline through day 5-7 for Part A and day 15-17 Part B.

• Number of patients with significant changes in Cholesterol levels

  Patients with Cholesterol exceeding or below normal values will be reported with the concentration in mg/dL

  Changes from baseline through day 5-7 for Part A and day 15-17 Part B.

• Number of patients with significant changes in Respiratory Rate

  Patients with changes in Respiratory Rate will be reported in count/min

  Changes from baseline through day 5-7 for Part A and day 15-17 Part B.

• Number of patients with significant changes in Pulse Rate

  Patients with changes in Pulse Rate will be reported in count/min

  Changes from baseline through day 5-7 for Part A and day 15-17 Part B.

• Number of patients with significant changes in Oral Temperature

  Patients with changes in Oral Temperature above normal will be reported in degrees Celcius (C)

  Changes from baseline through day 5-7 for Part A and day 15-17 Part B.

• Number of patients with significant changes in Blood Pressure

  Patients with changes in Supine Blood Pressure exceeding or below normal values will be reported in mmHg systolic over diastolic

  Changes from baseline through day 5-7 for Part A and day 15-17 Part B.

• Number of patients exhibiting changes in Physical Examination

  Number of patients exhibiting any changes in the physical examination during this period will be reported.

  Changes from baseline through day 5-7 for Part A and day 15-17 Part B.

Secondary Outcomes (8)

• Pharmacokinetic parameter: Mean Cmax +/- standard deviation

  This pharmacokinetic parameter will be assessed at the end of each of 6 cohorts in the SAD study (within 1-2 weeks of final blood sample collection) and 3 cohorts in the MAD study (within 1-2 weeks of final blood sample collection).

• Pharmacokinetic parameter: Mean AUC +/- standard deviation

  This pharmacokinetic parameter will be assessed at the end of each of 6 cohorts in the SAD study (within 1-2 weeks of final blood sample collection) and 3 cohorts in the MAD study (within 1-2 weeks of final blood sample collection).

• Pharmacokinetic parameter: Mean CL +/- standard deviation

  This pharmacokinetic parameter will be assessed at the end of each of 6 cohorts in the SAD study (within 1-2 weeks of final blood sample collection) and 3 cohorts in the MAD study (within 1-2 weeks of final blood sample collection).

• Pharmacokinetic parameter: Mean T1/2 +/- standard deviation

  This pharmacokinetic parameter will be assessed at the end of each of 6 cohorts in the SAD study (within 1-2 weeks of final blood sample collection) and 3 cohorts in the MAD study (within 1-2 weeks of final blood sample collection).

• Pharmacokinetic parameter: Mean Vss +/- standard deviation

  This pharmacokinetic parameter will be assessed at the end of each of 6 cohorts in the SAD study (within 1-2 weeks of final blood sample collection) and 3 cohorts in the MAD study (within 1-2 weeks of final blood sample collection).

Study Arms (2)

AER-271

EXPERIMENTAL

The experimental drug AER-271 will be administered in this Arm. In Part A single ascending doses will be administered by IV bolus infusion of AER-271 formulated in phosphate buffered normal saline over a 30-min period. In Part B multiple ascending doses of AER-271 will be administered by IV 30-min bolus infusion BID for 72 hours. AER-271 will also be administered as an initial bolus dose over 30-min then continuous infusion over 72 hours.

Drug: AER-271

Placebo

PLACEBO COMPARATOR

A placebo control will be administered in this Arm. In Part A phosphate buffered normal saline will be administered over a 30-min period. In Part B multiple doses of phosphate buffered normal saline will be administered by IV 30-min bolus infusion BID for 72 hours. This placebo will also be administered as an initial bolus dose over 30-min then continuous infusion over 72 hours. In both Parts, the volume of placebo administered will be the same as the Experimental Arm.

Drug: Placebo

Interventions

AER-271 DRUG

AER-271, the test article for this study.

AER-271

Placebo DRUG

Placebo control for this study.

Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Males or females, of any ethnic origin, between 18 and 45 years of age, inclusive, at Screening.
• Body mass index between 18.0 and 32.0 kg/m2, inclusive, at Screening.
• In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead ECG, vital sign measurements, and clinical laboratory evaluations (congenital nonhemolytic hyperbilirubinemia \[eg, suspected Gilbert's syndrome, as determined by total bilirubin and indirect bilirubin\] is acceptable) at Screening and/or Check-in, as assessed by the Investigator.
• Male subjects must be surgically sterile for at least 90 days or, for males capable of fathering children who are sexually active with female partners of childbearing potential, will use the required contraception methods, and will refrain from donating sperm from the time of the first dose until 90 days after the final dosing occasion.
• Female subjects must be:
• postmenopausal, defined as at least 12 months post cessation of menses (without an alternative medical cause) with a screening serum follicle-stimulating hormone (FSH) level \> 40 mIU/mL, or
• permanently sterile following hysterectomy, Essure procedure, bilateral salpingectomy, bilateral oophorectomy, or confirmed tubal occlusion (not tubal ligation).
• Venous access sufficient for IV infusions.
• Able to comprehend and willing to sign an Informed Consent Form (ICF) and to abide by the study restrictions.

You may not qualify if:

• Female subjects who are pregnant or lactating.
• Have any clinically significant abnormal physical examination finding at Check-in.
• Have any clinically significant medical history, as determined by the Investigator.
• History of seizure disorder, even if currently not receiving anticonvulsant medications.
• Part B only: Have acute suicidality, as evidenced by answering "yes" for Question 4 or Question 5 on the C-SSRS, indicating active suicidal ideation with any intent to act at Screening and Check-in.
• Part B only: Have a history of suicidal behavior such that a determination of "yes" is made on the Suicidal Behavior section of the C-SSRS for "Actual Attempt," "Interrupted Attempt," "Aborted Attempt," or "Preparatory Acts or Behavior" at Screening and Check-in.
• History or clinical manifestations of clinically significant metabolic (including diabetes mellitus, hypercholesterolemia, or dyslipidemia), hematologic, pulmonary, cardiovascular, gastrointestinal (cholecystectomy and appendectomy are acceptable), neurologic, hepatic, renal, urologic, immunologic, or psychiatric disorders (a history of mild depression, currently not receiving therapy, is acceptable), as determined by the Investigator.
• Have any clinically significant allergic condition (excluding non-active hay fever), as determined by the Investigator.
• Have a significant history of drug allergy, as determined by the Investigator.
• Have a clinically significant abnormality in oral temperature, respiratory rate, or supine pulse rate or blood pressure at Screening and prior to first dose that, in the opinion of the Investigator, increases the risk of participating in the study.
• Electrocardiogram findings that meet any of the following criteria at Screening or Day-1 (if out of range, ECG may be repeated twice, and the triplicate average will be used):
• QTcF \>450 msec confirmed by repeat measurement,
• QRS duration \> 120 msec,
• PR interval \>220 msec,
• findings which would make QTc measurements difficult or QTc data uninterpretable.

Sponsors & Collaborators

• Aeromics, Inc.: lead
• Covance: collaborator

Study Sites (1)

Covance Dallas

Dallas, Texas, 75247, United States

Location

MeSH Terms

Conditions

Stroke; Ischemic Stroke; Brain Edema

Interventions

AER-271

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Paul R McGuirk, PhD

  Aeromics, Inc.

  PRINCIPAL INVESTIGATOR

• Alex King, MD

  Covance

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The participants, care providers, investigators, outcome assessors, and safety monitoring board will be blind to the administration of AER-271.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: January 9, 2019
• First Posted: January 15, 2019
• Study Start: June 26, 2018
• Primary Completion: July 18, 2019
• Study Completion: August 28, 2019
• Last Updated: July 9, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)