Study of Merimepodib in Combination With Remdesivir in Adult Patients With Advanced COVID-19

A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of Oral Merimepodib in Combination With Intravenous Remdesivir in Adult Patients With Advanced Coronavirus Disease 2019 (COVID-19)

The purpose of this study is to assess the safety and efficacy of merimepodib (MMPD) oral solution when administered in combination with remdesivir in adult patients with advanced COVID-19.

Study Overview

• Status: Terminated
• Conditions: COVID-19
• Intervention / Treatment: Drug: Merimepodib; Drug: Remdesivir; Drug: Matching Placebo

Detailed Description

This phase 2 randomized, double-blind, placebo-controlled study will enroll approximately 80 adult patients with advanced coronavirus disease 2019 (COVID-19). Approximately 80 patients will be randomized 1:1 to receive oral administration of MMPD + remdesivir or placebo + remdesivir. The first 40 patients will have a score of 3 or 4 on the National Institute of Allergy and Infectious Disease (NIAID) 8-point ordinal scale and at least one of the following: fever, cough, sore throat, malaise, headache, muscle pain, shortness of breath at rest or with exertion, confusion or symptoms of severe lower respiratory symptoms; the final 40 patients will have a score of 3 on the NIAID scale.

Study subjects will undergo screening evaluations prior to the first dose of study drug. Study drug treatment (MMPD or placebo) will continue for 10 days, unless the patient is discharged from the hospital before completing the 10-day randomized treatment period. Both treatment arms will also receive remdesivir per the Emergency Use Authorization labeling. Evaluations will be performed on Days 0-10 and every day thereafter until the subject no longer requires any form of respiratory support or they reach the last planned day of in-person study assessments and still require respiratory support. The final in-person study evaluations will be performed 4 weeks after completion of study drug (MMPD or placebo) treatment (Day 37). The final study evaluation will be a telephone call on Day 56.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic in Arizona
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Holy Cross Hospital
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic in Florida
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Atlantic Health System / Morristown Medical Center
    • Summit, New Jersey, United States, 07901
      • Atlantic Health System / Overlook Medical Center
  • Texas
    • Austin, Texas, United States, 78705
      • St. David's Medical Center
    • Austin, Texas, United States, 78704
      • St. David's South Austin Medical Center
    • Houston, Texas, United States, 77004
      • HCA Houston Healthcare Medical Center
    • Texas City, Texas, United States, 77591
      • HCA Houston Healthcare Mainland

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• At least 18 years old
• Confirmed SARS-CoV-2 viral infection
• Advanced COVID-19 with score of 3 or 4 on NIAID scale (first 40 patients) or score of 3 on NIAID scale (last 40 patient
• Has at least one of the following: fever, cough, sore throat, malaise, headache, muscle pain, shortness of breath, confusion or severe lower respiratory symptoms
• Off antiviral medications at least 24 hours prior to first dose of study drug (except for remdesivir)
• Able to provide consent
• Agree to appropriate methods of contraception

Exclusion Criteria:

• In critical condition or has ARDS
• On invasive mechanical ventilation or ECMO
• Bacterial or fungal infection
• Pregnant or lactating (women)
• ALT >5x ULN, bilirubin >2x ULN, INR outside of normal limits at screening
• eGFR <30 mL/min
• Clinically relevant serious co-morbid medical conditions
• Treatment with any immunosuppressive therapy within 30 days prior to screening
• Treatment with another investigational drug within 30 days or 5 half-lives of drug prior to screening
• Prior treatment with the study drug (MMPD) or treatment with remdesivir more than 24 hours prior to the first randomized dose of study drug
• Known hypersensitivity to the inactive ingredients in the study drug (MMPD or placebo) or any ingredient of remdesivir

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: MMPD + remdesivir; Study subjects will receive MMPD oral solution 3 times per day for 10 days unless discontinued early. Study subjects will also receive remdesivir infusion once a day for 5 days. If a subject does not demonstrate clinical improvement, remdesivir treatment may be extended for up to 5 additional days (for a total of up to 10 days).	Drug: Merimepodib; 400 mg (total daily dose of 1200 mg) for 10 days; Other Names: VX-497; Drug: Remdesivir; 200 mg loading dose on Day 0 followed by 100 mg daily dose for 4 days. If a subject does not demonstrate clinical improvement, 100 mg daily dose may be extended for up to 5 additional days (for a total of up to 10 days)
Placebo Comparator: Placebo + remdesivir; Study subjects will receive matching placebo oral solution 3 times per day for 10 days unless discontinued early. Study subjects will also receive remdesivir infusion once a day for 5 days. If a subject does not demonstrate clinical improvement, remdesivir treatment may be extended for up to 5 additional days (for a total of up to 10 days).	Drug: Remdesivir; 200 mg loading dose on Day 0 followed by 100 mg daily dose for 4 days. If a subject does not demonstrate clinical improvement, 100 mg daily dose may be extended for up to 5 additional days (for a total of up to 10 days); Drug: Matching Placebo; 0 mg (total daily dose of 0 mg) for 10 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects not hospitalized or, if hospitalized, free of respiratory failure	Proportion of subjects alive at Day 28 who are not hospitalized or if hospitalized are free of respiratory failure	Day 0 to Day 28
Adverse Events	Number of Adverse Events (AEs) and number & percentage of subjects experiencing AEs after administration of the first dose of study drug	Day 0 to Day 56

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
National Institute of Allergy and Infectious Disease (NIAID) 8-Point Ordinal Scale	Change in NIAID 8-point ordinal scale, where 1=Death and 8=Not hospitalized, no limitations on activities	Day 0 to Day 28
Temperature	Duration of fever	Day 0 to Day 37
Death	Number of deaths	Day 0 to Day 56
Mechanical ventilation	Need and duration of mechanical ventilation	Day 0 to Day 56
Vasopressor Support	Duration of vasopressor support	Day 0 to Day 56
Oxygen Therapy	Duration of oxygen therapy via mechanical ventilation, face mask or nasal cannula	Day 0 to Day 37
Cessation of Viral Shedding	Time to cessation of viral shedding based on absence of SARS-CoV-2 in a PCR based COVID-19 test	Day 0 to Day 37
Change in Oxygen Saturation/Fraction of Inspired Oxygen	Change in SpO2/FiO2	Day 0 to Day 37

Collaborators and Investigators

• Sponsor: ViralClear Pharmaceuticals, Inc.
• Investigators: Study Director: Andrew Badley, MD, Mayo Clinic

Study record dates

Study Major Dates

• Study Start (Actual): June 16, 2020
• Primary Completion (Actual): December 1, 2020
• Study Completion (Actual): December 1, 2020

Study Registration Dates

• First Submitted: April 28, 2020
• First Submitted That Met QC Criteria: May 28, 2020
• First Posted (Actual): June 1, 2020

Study Record Updates

• Last Update Posted (Actual): December 8, 2020
• Last Update Submitted That Met QC Criteria: December 4, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: Coronavirus; SARS-Cov-2; Advanced Coronavirus Disease 2019
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Remdesivir
• Other Study ID Numbers: VC-02-01

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