Clinical trial NCT04435522: Maraviroc in Patients With Moderate and Severe COVID-19
Official title: Open-Label Study of Maraviroc in Hospitalized Individuals Diagnosed With SARS-CoV-2
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: COVID
Keywords: Maraviroc
CCR5 Antagonist
Lead sponsor: Rhode Island Hospital
Sponsor class: OTHER
First posted: 2020-06-17
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: This pilot study seeks to establish that selective blockade of the CCR5/CCL5 axis as well as the potential anti-viral properties of Maraviroc may reduce disease severity. This proof-of-concept effort seeks to correlate differences in clinical outcomes to differential cytokine expression in the setting of CCR5 antagonism in patients infected with SARS-CoV-2. Maraviroc is FDA-approved for the treatment of CCR5-tropic HIV-1 and has a well-documented safety and tolerability record in previous trials in immunocompromised HIV patients. Maraviroc was not shown to have significant effect on the QT segment, can be delivered via oral formulation, and can be delivered safely to both patients with end-stage renal disease and dependence on hemodialysis12. For these reasons, Maraviroc is an ideal candidate to study as a potential therapy for hospitalized patients with moderate-to-severe COVID-19.

The primary objective is to establish whether Maraviroc, used at its approved dosage for HIV, is safe, tolerable, and effective in hospitalized patients with SARS-CoV-2. The secondary objective is to investigate the relationship between reduction of inflammatory markers (such as IL-6, CCL5, etc.) and clinical outcomes, including avoidance of respiratory decompensation and death.

This is a single-center, single-arm, open-label trial. Sixteen hospitalized patients will be enrolled. Screening data will be reviewed to determine subject eligibility. Subjects who meet all inclusion criteria and none of the exclusion criteria will be approached for consent prior to entering the study. Each subject will receive 7 days of Maraviroc twice daily. Each subject will have blood samples checked at time of enrollment (Day 0), Day 3, Day 7, and Day 15 or time of live discharge (whichever comes first) of the study. The total duration of subject participation will be five weeks. The total duration of the study is expected to be 16 weeks.

Eligibility criteria: 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

Primary outcomes:
measure: Rate of Completion
timeFrame: 7 days
measure: Clinical Improvement at Day 7
timeFrame: 7 days
Secondary outcomes:
measure: Mortality
timeFrame: 28 days
measure: Median Time to >= 2 Point Improvement in Clinical Score.
timeFrame: 28 Days
Other outcomes:
Locations:
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
Study officials:
affiliation: Warren Alpert Medical School and School of Public Health, Brown University
name: Philip A Chan, MD
role: PRINCIPAL_INVESTIGATOR
References: