Maraviroc in Patients With Moderate and Severe COVID-19

Study Overview
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Brief Summary
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Maraviroc, a C-C Chemokine Receptor 5 (CCR5) antagonist, is well-tolerated without significant side effects in its current use in patients with HIV. CCR5 antagonism prior to the 'second wave' of inflammatory mediator expression in SARS-CoV-2 may reverse lymphoid depletion and may alter cell trafficking of inflammatory cells, both increasing viral control capacity and dampening damage to lung tissue, respectively. This study seeks to establish whether one week of treatment with Maraviroc, used at its approved dosage for HIV, is safe and tolerable in patients with SARS-CoV-2.

Official Title
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Open-Label Study of Maraviroc in Hospitalized Individuals Diagnosed With SARS-CoV-2

Conditions
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COVID

Intervention / Treatment
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* Drug: Maraviroc


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ≥ 18 years of age at time of screening Documentation of a SARS-CoV-2 diagnosis as evidenced by positive SARS-CoV-2 PCR within twelve days at time of screening Chest radiography consistent with multi-focal pneumonia or air-space disease Written informed consent obtained from subject and ability for subject to comply with the requirements of the study. Subject able to safely swallow pills or receive Maraviroc through a nasogastric or orogastric tube. Exclusion Criteria: Subjects who are pregnant, breastfeeding, or unwilling to practice birth control during participation in the study. Subjects with the presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data. This includes, but is not limited to, recent myocardial infarction in past 6 months, neurological, psychiatric, endocrine, or neoplastic diseases that are judged to interfere with participation in the study. Subjects with known diagnosis of human immunodeficiency virus infection (HIV) Subjects enrolled in another clinical trial (including one for COVID-19) that excludes participation in other trials or includes a potent CYP3A inhibitor or inducer (e.g. lopinavir-ritonavir). Subjects with ESRD or severe renal failure who are taking potent (moderate or strong) CYP3A inhibitors or inducers

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Maraviroc Treatment<br>Maraviroc 300 mg Twice Daily | Drug: Maraviroc<br>* Maraviroc will be administered for seven days. Biomarkers of disease will be checked at time of enrollment, during and at the conclusion of therapy. The cytokine panel will consist of CCL5, IL-6, and Chitinase 3-like 1(Chi3l1).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Completion | Rate of subjects who complete the 7-day course of Maraviroc without discontinuation for serious adverse event or death. | 7 days | 
| Clinical improvement at Day 7 | Percent of patients at Day 7 from enrollment achieving reduction of two points on a seven-category ordinal scale (defined below). Ordinal scale: 1, not hospitalized with resumption of normal activities; 2, not hospitalized, but unable to resume normal activities OR hospitalized pending disposition, not requiring COVID-related care; 3, hospitalized, not requiring supplemental oxygen; 4, hospitalized, requiring supplemental oxygen; 5, hospitalized, requiring nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both; 6, hospitalized, requiring ECMO, invasive mechanical ventilation, or both; and, 7, death. | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Chitinase 3-like 1(Chi3l1) (ng/mL) | Measurement of Chi3l1 before, during and at completion of therapy. | 7 days | 
| Change in Interleukin-6 (IL-6) (pg/mL) | Measurement of IL-6 before, during and at completion of therapy. | 7 Days | 
| Change in CCL5 (RANTES) (ng/mL) | Measurement of CCL5 before, during and at completion of therapy. | 7 Days | 
| Mortality | 7-, 14- and 28-day all-cause-mortality | 28 days | 
| Time to Discharge | Time to improvement to Score of 2 or less (Days) | 28 days | 
| Days on mechanical ventilation |  | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Maraviroc, CCR5 Antagonist