Trial to Evaluate the Safety and Efficacy of Maraviroc in Patients Hospitalized for Coronavirus Disease 2019 (COVID-19) (COVIMAR)

• ClinicalTrials.gov Identifier: NCT04710199
• Recruitment Status: Recruiting
• First Posted: January 14, 2021
• Last Update Posted: April 6, 2021
• Sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
• Information provided by (Responsible Party): Fundación Pública Andaluza para la gestión de la Investigación en Sevilla

Tracking Information

• First Submitted Date: January 5, 2021
• First Posted Date: January 14, 2021
• Last Update Posted Date: April 6, 2021
• Actual Study Start Date: February 8, 2021
• Estimated Primary Completion Date: August 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 13, 2021)

Evaluate the efficacy of Maraviroc in SARS-CoV-2 infected patients hospitalized for COVID-19 using the Ordinal scale. [ Time Frame: Baseline, change from baseline at 7 days, change from baseline at 14 days, change from baseline at 21 days and change from baseline at 28 days ]

Ordinal scale: (1) Not hospitalized, without limitations in activities; (2) Not hospitalized, limitations in activities; (3) Hospitalized, with no oxygen supplement requirement; (4) Hospitalized, requiring supplemental oxygen; (5) Hospitalized, with non-invasive ventilation or high flow oxygen device or oxygen mask with reservoir); (6) Hospitalized, with invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); (7) Death. treatment versus standard treatment, in relation to the clinical progression of COVID-19 in hospitalized patients.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 13, 2021)

• Analyze changes in analytical variables: changes in ambient air oxygen saturation (SatO2),related to the progression of COVID-19. [ Time Frame: Baseline, change from baseline at 7 days, change from baseline at 14 days, change from baseline at 21 days and change from baseline at 28 days ]
  Analytical variables related to the progression of COVID-19: changes in ambient air oxygen saturation (SatO2) (mmHg).
• Study the variation in the number of biomarkers of inflammation. [ Time Frame: Baseline, change from baseline at 7 days, change from baseline at 14 days, change from baseline at 21 days and change from baseline at 28 days ]
  Changes in levels of macrophage inflammatory proteins-1 α (MIP-1 α), MIP-1 β, regulated on activation normal T cell expressed and secreted (RANTES), interleukin-6 (IL-6), IL-8, interferon-inducible protein 10 (IP-10), IL-1β, TNF-α, gamma interferon (IFN-γ), soluble cluster of differentiation 25 (CD25), β2 microglobulin, dimers D, soluble cluster of differentiation 14 (CD14), soluble cluster of differentiation 40 (CD40) ligand and soluble cluster of differentiation 163 (CD163).
• Analyze changes in the number of innate immune activation (monocytes and dendritic cells) and adaptive (T lymphocytes). [ Time Frame: Baseline, change from baseline at 7 days, change from baseline at 14 days, change from baseline at 21 days and change from baseline at 28 days ]
  Changes in levels subpopulations (classical, intermediate and non-classical monocytes) and activation markers in them. Dendritic cell subpopulations (myeloid and plasmacytoid dendritic cells) and their activation markers. Subpopulations of T lymphocytes (naive, central memory, effector memory and terminally differentiated) and markers of activation, senescence and wasting in them.
• Quantify the number of immunomodulatory treatments added to therapy [ Time Frame: Baseline, change from baseline at 7 days, change from baseline at 14 days, change from baseline at 21 days and change from baseline at 28 days ]
  Quantification of additional treatments added to the administered therapy , this is immunomodulatory treatments such as: IL-6,or IL-1 inhibitors, high-dose corticosteroids, anti-tumor necrosis factor (anti-TNF) antibodies, janus kinases (JAK) kinase inhibitors or any other immunomodulatory effect and / or under investigation
• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: Baseline, change from baseline at 7 days, change from baseline at 14 days, change from baseline at 21 days and change from baseline at 28 days ]
  Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
• Analyze changes in analytical variables:changes in neutrophils, related to the progression of COVID-19. [ Time Frame: Baseline, change from baseline at 7 days, change from baseline at 14 days, change from baseline at 21 days and change from baseline at 28 days ]
  Changes in levels of neutrophils in blood (x10e9/L)
• Analyze changes in analytical variables: changes in platelets, related to the progression of COVID-19. [ Time Frame: Baseline, change from baseline at 7 days, change from baseline at 14 days, change from baseline at 21 days and change from baseline at 28 days ]
  Changes in levels of platelets in blood (x10e9/L)
• Analytical variables related to the progression of COVID-19: changes in lactate dehydrogenase (LDH). [ Time Frame: Baseline, change from baseline at 7 days, change from baseline at 14 days, change from baseline at 21 days and change from baseline at 28 days ]
  Changes in levels of lactate dehydrogenase in blood (U/L)
• Analyze changes in analytical variables: changes in C-reactive protein, related to the progression of COVID-19. [ Time Frame: Baseline, change from baseline at 7 days, change from baseline at 14 days, change from baseline at 21 days and change from baseline at 28 days ]
  Changes in levels of C-reactive protein in blood (mg/L)

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Trial to Evaluate the Safety and Efficacy of Maraviroc in Patients Hospitalized for Coronavirus Disease 2019 (COVID-19)
• Official Title: Proof-of-concept Trial to Evaluate the Safety and Efficacy of Maraviroc in Severe Acute Respiratory Syndrome (SARS) Coronavirus-2 (CoV-2) Infected Patients Hospitalized for COVID-19
• Brief Summary: Maraviroc (MVC) is a drug, very well tolerated, it has been seen that MVC has properties of modulating the immune system, exerting an anti-inflammatory effect in different diseases. In COVID-19, very high levels of inflammation occur that cause organs and systems to be damaged. MVC could reduce this inflammation achieving a better prognosis of COVID-19.
• Detailed Description: In this clinical trial the investigators want to evaluate if standard treatment together with Maraviroc (MVC) compared to standard treatment alone, achieves better clinical evolution in participants hospitalized for COVID-19.
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

In this clinical trial, standard treatment together with Maraviroc (MVC) is evaluated compared to treatment alone.

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Virus Diseases

Intervention

• Drug: Maraviroc experimental group
  Maraviroc tablet, 600 mg milligram, oral use,daily during 14 days.
• Other: Standard treatment
  It is based on the treatment protocol for hospitalized COVID-19 patients and that will depend on the clinical status of the patient.

Study Arms

• Experimental: Maraviroc experimental group
  Maraviroc tablet combined with standard treatment
  Intervention: Drug: Maraviroc experimental group
• Standard treatment
  It is based on the treatment protocol for hospitalized COVID-19 patients and that will depend on the clinical status of the patient.
  Intervention: Other: Standard treatment

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 13, 2021): 40
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 2021
• Estimated Primary Completion Date: August 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Subjects aged ≥ 18 years.
• Infection confirmed by SARS-CoV-2 by polymerase chain reaction (PCR) or by antigen test, in this case, at least in the first seven days after the onset of symptoms and in any case up to 3 days before randomization.
• Hospitalized or emergency patient in hospitalization phase.
• Mild / moderate pneumonia, with fever, persistent cough and severe asthenia, confirmed by imaging tests (conventional radiology or computerized axial tomography (CT)) with ambient air oxygen saturation (SatO2)> 94%.
• Less than 12 days from the onset of symptoms.
• Women of childbearing potential must have a negative serum or urine pregnancy test prior to inclusion in the study and must commit to using highly effective contraceptive methods (intrauterine device, bilateral tubal occlusion, vasectomized partner, and sexual abstinence).
• Accepts written consent or oral informed in the case that due to the relevant security protocols, written consent is not possible.

Exclusion Criteria:

• Patient with severe pneumonia confirmed by imaging test (conventional radiology or computerized axial tomography (CT)) with ambient air oxygen saturation (SatO2) ≤94%.
• Another acute active infection other than that produced by SARS-CoV-2.
• Chronic renal failure (estimated glomerular filtration ≤ 30 ml / min / 1.73 m2 or receiving renal replacement therapy in any of its modalities).
• Known HIV infection. Unless the patient has> 500 CD4 + / mm3 and an undetectable viral load for more than 6 months.
• Active co-infection with known hepatitis B or C viruses.
• Cirrhosis, portal hypertension and / or hypersplenism of any etiology.
• Past or current neoplasms subsidiary to treatment with steroids, immunomodulators or chemotherapy
• Grade 3 or 4 laboratory abnormalities.
• Concomitant use of drugs with major pharmacological interactions with the study drugs, according to the respective technical specifications of the products.
• Estimated creatinine clearance <50ml / min.
• Pregnancy.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Jose Manuel Lomas, MD; 0034955012010; jlomascabezas@yahoo.es

Contact: Clara Mª Rosso, MD; 0034955012144; claram.rosso@juntadeandalucia.es

• Listed Location Countries: Spain

Administrative Information

• NCT Number: NCT04710199
• Other Study ID Numbers: COVIMAR
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
• Study Sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
• Collaborators: Not Provided

Investigators

• Principal Investigator: Jose Manuel Lomas, MD; Hospitales Universitarios Virgen del Rocío

• PRS Account: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
• Verification Date: April 2021