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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

Phase 2
Active, not recruiting
Conditions
COVID-19
Interventions
Drug: Placebo
Registration Number
NCT05815485
Lead Sponsor
The University of Texas Medical Branch, Galveston
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
144
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 & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Phase 3 placeboPlacebo-
Phase 2 placeboPlacebo-
Phase 2 azeliragonAzeliragon-
Phase 3 azeliragonAzeliragon-
Primary Outcome Measures
NameTimeMethod
Frequency of Adverse Events (AEs) (Phase 2 only)Up to 28 days post-treatment

Including overall, treatment-related, Grade 3 or higher in severity, serious AEs (SAEs), fatal, and those resulting in treatment discontinuation

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)Day 14 of hospitalization

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

Secondary Outcome Measures
NameTimeMethod
Frequency of AEs (Phase 3 only)Day 14 of hospitalization

Including: overall, treatment-related, Grade 3 or higher in severity, serious, fatal, and those resulting in treatment discontinuation

Frequency of each AKI Kidney Disease Improving Global Outcomes (KDIGO) scale scores (Phase 3 only)Day 14 of hospitalization

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

Frequency of sustained renal function (Phase 3 only)Day 14 of hospitalization

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

Number of days in ICU (Phase 3 only)Day 14 of hospitalization
Frequency of renal function after prior AKI of stage 2 or higher (Phase 3 only)Day 14 of hospitalization

Serum creatinine levels to \< 1.5 times baseline level

Frequency of Intensive Care Unit (ICU) admission (Phase 3 only)Day 14 of hospitalization
Length of hospitalization (Phase 3 only)Up to 14 days

Trial Locations

Locations (3)

Rush University

🇺🇸

Chicago, Illinois, United States

University of Michigan

🇺🇸

Ann Arbor, Michigan, United States

University of Texas Medical Branch

🇺🇸

Galveston, Texas, United States

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