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

• ClinicalTrials.gov Identifier: NCT05815485
• Recruitment Status: Recruiting
• First Posted: April 18, 2023
• Last Update Posted: October 31, 2023
• Sponsor: Salim S. Hayek
• Information provided by (Responsible Party): Salim S. Hayek, University of Michigan

Tracking Information

• First Submitted Date: April 13, 2023
• First Posted Date: April 18, 2023
• Last Update Posted Date: October 31, 2023
• Actual Study Start Date: May 4, 2023
• Estimated Primary Completion Date: April 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 13, 2023)

• Frequency of Adverse Events (AEs) (Phase 2 only) [ Time Frame: 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) [ Time Frame: 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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 27, 2023)

• Frequency of each AKI Kidney Disease Improving Global Outcomes (KDIGO) scale scores (Phase 3 only) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: Day 14 of hospitalization ]
  Serum creatinine levels to < 1.5 times baseline level
• Frequency of Intensive Care Unit (ICU) admission (Phase 3 only) [ Time Frame: Day 14 of hospitalization ]
• Number of days in ICU (Phase 3 only) [ Time Frame: Day 14 of hospitalization ]
• Frequency of AEs (Phase 3 only) [ Time Frame: 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) [ Time Frame: Up to 14 days ]

Original Secondary Outcome Measures (submitted: April 13, 2023)

• Frequency of each AKI Kidney Disease Improving Global Outcomes (KDIGO) scale scores (Phase 3 only) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: Day 14 of hospitalization ]
  Serum creatinine levels to < 1.5 times baseline level
• Frequency of Intensive Care Unit (ICU) admission (Phase 3 only) [ Time Frame: Day 14 of hospitalization ]
• Number of days in ICU (Phase 3 only) [ Time Frame: Day 14 of hospitalization ]
• World Health Organization (WHO) (Phase 3 only) COVID severity [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: Up to 14 days ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Official Title: 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3

Study Design

Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Azeliragon and placebo will be dispensed and labeled by the unblinded research pharmacist at each site in a blinded manner that will not reveal if the product dispensed is active or placebo.

Primary Purpose: Treatment

• Condition: COVID-19

Intervention

• Drug: Azeliragon
  30 mg twice daily for 5 days followed by 20 mg once daily for 5 days or until discharge (whichever is earliest).
• Drug: Placebo
  Twice daily for 5 days then 1 time daily for 5 days or until discharge (whichever is earliest).

Study Arms

• Experimental: Phase 2 azeliragon
  Intervention: Drug: Azeliragon
• Placebo Comparator: Phase 2 placebo
  Intervention: Drug: Placebo
• Experimental: Phase 3 azeliragon
  Intervention: Drug: Azeliragon
• Placebo Comparator: Phase 3 placebo
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 13, 2023): 144
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 2026
• Estimated Primary Completion Date: April 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Pennelope Kunkle; 734-936-2813; penegonz@umich.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05815485
• Other Study ID Numbers: HUM00221960
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Salim S. Hayek, University of Michigan
• Original Responsible Party: Same as current
• Current Study Sponsor: Salim S. Hayek
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Salim Hayek, MD; University of Michigan

• PRS Account: University of Michigan
• Verification Date: October 2023