COVID
Conditions
Keywords
Maraviroc, CCR5 Antagonist
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.
Interventions
DRUGMaraviroc
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).
Sponsors
Rhode Island Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Completion | 7 days | Rate of subjects who complete the 7-day course of Maraviroc (or shorter if discharged from hospital prior to 7 days) without discontinuation for serious adverse event or death. |
| Clinical Improvement at Day 7 | 7 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mortality | 28 days | 7-, 14- and 28-day all-cause-mortality |
| Median Time to >= 2 Point Improvement in Clinical Score. | 28 Days | If no clinical improvement of \>=2 points met by day 28, patient outcome censored |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Maraviroc Treatment Maraviroc 300 mg Twice Daily
Maraviroc: Maraviroc will be administered for seven days. Biomarkers of disease will be checked at time of enrollment, during and at the conclusion of therapy. | 9 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Maraviroc Treatment |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Region of Enrollment United States | 9 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 9 |
| other Total, other adverse events | 1 / 9 |
| serious Total, serious adverse events | 1 / 9 |
Outcome results
Primary
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.
Time frame: 7 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Maraviroc Treatment | Clinical Improvement at Day 7 | 3 Participants |
Primary
Rate of Completion
Rate of subjects who complete the 7-day course of Maraviroc (or shorter if discharged from hospital prior to 7 days) without discontinuation for serious adverse event or death.
Time frame: 7 days
Population: Patients who received at least one dose of Maraviroc
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Maraviroc Treatment | Rate of Completion | 7 Participants |
Secondary
Median Time to >= 2 Point Improvement in Clinical Score.
If no clinical improvement of \>=2 points met by day 28, patient outcome censored
Time frame: 28 Days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Maraviroc Treatment | Median Time to >= 2 Point Improvement in Clinical Score. | 8 Days |
Secondary
Mortality
7-, 14- and 28-day all-cause-mortality
Time frame: 28 days
Population: Population that received at least 1 dose of Maraviroc
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Maraviroc Treatment | Mortality | 7-Day Mortality | 0 Participants |
| Maraviroc Treatment | Mortality | 14-Day Mortality | 0 Participants |
| Maraviroc Treatment | Mortality | 28-Day Mortality | 0 Participants |