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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Azeliragon
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Azeliragon, Acute Kidney Injury