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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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)

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Merimepodib
* Drug: Matching Placebo
* Drug: Remdesivir


Participation Criteria
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Eligibility Criteria
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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

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: Parallel Assignment
Interventional Model Description: Eligible study subjects will be randomized 1:1 to receive oral administration of study drug or placebo. Both treatment arms will also receive remdesivir.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: MMPD + remdesivir<br>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<br>* 400 mg (total daily dose of 1200 mg) for 10 days<br>* Other names: VX-497;Drug: Remdesivir<br>* 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)<br>|
| Placebo Comparator: Placebo + remdesivir<br>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: Matching Placebo<br>* 0 mg (total daily dose of 0 mg) for 10 days<br>Drug: Remdesivir<br>* 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)<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Coronavirus, Advanced Coronavirus Disease 2019, SARS-Cov-2