A Randomized, Double-Blind, Placebo-Controlled Phase 2/3 Study to Determine the Safety and Effectiveness of Azeliragon in the Treatment of Patients Hospitalized for Coronavirus Disease 2019 (COVID-19) or Pneumonia

A new drug called azeliragon could be used to treat patients with COVID-19 or other pneumonia infections but the researchers don't know. In this study, they are learning the effects of azeliragon patients hospitalized for COVID-19 or pneumonia.

Study Overview

• Status: Active, not recruiting
• Conditions: COVID-19
• Intervention / Treatment: Drug: Azeliragon; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 144
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Texas
    • Galveston, Texas, United States, 77555
      • University of Texas Medical Branch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with at least two of the following signs or symptoms: cough, chest pain, shortness of breath, hypoxia (oxygen saturation <90%)
• Clinical diagnosis of pneumonia or COVID-19 during the first 48 hours of hospitalization.
• Patients admitted to the hospital within the previous 48 hours (from time of admission to initial treatment dose.)
• Provide informed consent to participate in the study (by participant or legally-acceptable representative).

Exclusion Criteria:

• Patients for whom intubation within 24 hours of admission is considered likely.
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3x upper limit of normal (ULN), OR total serum bilirubin >2x ULN.
• Patients who were receiving dialysis as a regular treatment at the time of admission. (Participants are not excluded for historic need for dialysis.)
• Chronic liver disease with Child-Pugh class B of (7 to 9) or higher.
• Patients with an electrocardiogram (ECG) corrected QT interval (QTc) > 500 ms.
• Patients requiring treatment with strong inhibitors of CYP2C8
• Females of childbearing potential who are pregnant, breastfeeding, and/or not using a highly-effective method of contraception (consistent with local regulations regarding the methods of contraception for those participating in clinical studies, including willingness to use 2 acceptable forms of contraception from screening until after the end of drug treatment. Acceptable forms include tubal ligation, male latex condom with or without spermicide, partner's vasectomy, diaphragm with spermicide, intrauterine device, cervical cap/sponge with spermicide, contraceptive sponge, female condom, hormonal contraceptive including oral, transdermal, vaginal ring, subcutaneous injection, or implanted rod.)
• Allergy to azeliragon or formulation excipients in the azeliragon or placebo capsule.
• Concurrent participation in another device or drug trial for treatment purposes. Trials with devices intended for diagnostic purposes only are allowable..
• Any other condition, including abnormal laboratory values that, in the judgment of the investigator, could put the participant at increased risk, or would interfere with the conduct or planned analysis of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 2 azeliragon	Drug: Azeliragon; 30 mg twice daily for 5 days followed by 20 mg once daily for 5 days or until discharge (whichever is earliest).
Placebo Comparator: Phase 2 placebo	Drug: Placebo; Twice daily for 5 days then 1 time daily for 5 days or until discharge (whichever is earliest).
Experimental: Phase 3 azeliragon	Drug: Azeliragon; 30 mg twice daily for 5 days followed by 20 mg once daily for 5 days or until discharge (whichever is earliest).
Placebo Comparator: Phase 3 placebo	Drug: Placebo; Twice daily for 5 days then 1 time daily for 5 days or until discharge (whichever is earliest).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of Adverse Events (AEs) (Phase 2 only)	Including overall, treatment-related, Grade 3 or higher in severity, serious AEs (SAEs), fatal, and those resulting in treatment discontinuation	Up to 28 days post-treatment
Death, need for mechanical ventilation or Acute Kidney Injury (AKI) of stage 2 or higher per Kidney Disease Improving Global Outcomes (KDIGO) scale (Phase 3 only)	The primary outcome is a composite endpoint, which is defined as the need for mechanical ventilation, in-hospital death or AKI of stage 2 or higher per KDIGO scale. There are 3 stages in the KDIGO scale with stage 3 being the worst (corresponds to renal failure). KDIGO Scale definitions: Stage 2 - Serum Creatinine 2-2.9 times baseline Stage 3 - Serum Creatinine 3 times baseline or Increase in serum creatinine to ≥4 mg/dL or Initiation of renal replacement therapy	Day 14 of hospitalization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of each AKI Kidney Disease Improving Global Outcomes (KDIGO) scale scores (Phase 3 only)	There are 3 stages in the KDIGO scale with stage 3 being the worst (corresponds to renal failure). Stage 1- serum creatinine 1.5 to 1.9 times baseline OR an increase in serum creatinine ≥ 0.3 mg/dL OR urine output < 0.5ml/kg/hour for 6-12 hours. Stage 2- serum creatinine 2.0-2.9 times baseline OR urine output <0.5mg/kg/hour for ≥ 12 hours Stage 3- serum creatinine 3.0 times baseline (or serum creatinine of more than or equal to 4.0 mg/dl with an acute increase of at least 0.5 mg/dl) (OR) Urine output less than 0.3 ml/kg/hour for 24 hours or anuria for 12 hours or new renal replacement therapy	Day 14 of hospitalization
Frequency of sustained renal function (Phase 3 only)	Renal function defined by no increase in serum creatinine of ≥0.3mg/dL during any 48hr period, AND no increase in serum creatinine of ≥1.5 times	Day 14 of hospitalization
Frequency of renal function after prior AKI of stage 2 or higher (Phase 3 only)	Serum creatinine levels to < 1.5 times baseline level	Day 14 of hospitalization
Frequency of Intensive Care Unit (ICU) admission (Phase 3 only)		Day 14 of hospitalization
Number of days in ICU (Phase 3 only)		Day 14 of hospitalization
Frequency of AEs (Phase 3 only)	Including: overall, treatment-related, Grade 3 or higher in severity, serious, fatal, and those resulting in treatment discontinuation	Day 14 of hospitalization
Length of hospitalization (Phase 3 only)		Up to 14 days

Collaborators and Investigators

• Sponsor: The University of Texas Medical Branch, Galveston
• Investigators: Principal Investigator: Lucas S. Blanton, MD, University of Texas

Study record dates

Study Major Dates

• Study Start (Actual): May 4, 2023
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: April 13, 2023
• First Submitted That Met QC Criteria: April 13, 2023
• First Posted (Actual): April 18, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 26, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Azeliragon; Acute Kidney Injury
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19; Pneumonia
• Other Study ID Numbers: 24-0103; HUM00221960 (Other Identifier: University of Michigan)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No