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)
Study Details
Study Description
Brief Summary
A new drug called azeliragon could be used to treat patients with COVID-19 but the researchers don't know. In this study, they are learning the effects of azeliragonon patients hospitalized for COVID-19.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2/Phase 3 |
Study Design
Arms and Interventions
| 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).
|
Outcome Measures
Primary Outcome Measures
- 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
- 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
- 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]
- Number of days in ICU (Phase 3 only) [Day 14 of hospitalization]
- World Health Organization (WHO) (Phase 3 only) COVID severity [Day 14 of hospitalization]
As measured by WHO ordinal scale for clinical improvement ranging from 0-8, and the higher numbers have worse outcomes
- 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
- Length of hospitalization (Phase 3 only) [Up to 14 days]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patients with a laboratory confirmed Severe Acute Respiratory Syndrome (SARS)-coronavirus 2 (CoV-2) infection and admitted primarily for the treatment of COVID-19. Co-administration of FDA approved antivirals or monoclonal antibodies is permitted.
-
Patients admitted to the hospital within the previous 48 hours (from time of admission to initial treatment dose.)
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Provide informed consent to participate in the study (by participant or legally-acceptable representative).
Exclusion Criteria:
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Patients for whom intubation within 24 hours of admission is considered likely.
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Severe chronic respiratory disease, defined by any supplemental oxygen requirement prior to incident COVID-19 infection.
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Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3x upper limit of normal (ULN), OR total serum bilirubin >2x ULN.
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Patients who were receiving dialysis as a regular treatment at the time of admission. (Participants are not excluded for historic need for dialysis.)
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Chronic liver disease with Child-Pugh class B of (7 to 9) or higher.
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Patients with an electrocardiogram (ECG) corrected QT interval (QTc) > 500 ms.
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Patients requiring treatment with strong inhibitors of CYP2C8
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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.)
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Allergy to azeliragon or formulation excipients in the azeliragon or placebo capsule.
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Concurrent participation in another device or drug trial.
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Rush University | Chicago | Illinois | United States | 60612 |
| 2 | University of Michigan | Ann Arbor | Michigan | United States | 48109 |
Sponsors and Collaborators
- Salim S. Hayek
Investigators
- Study Chair: Salim Hayek, MD, University of Michigan
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- HUM00221960