COVID-19 Clinical Trials and Expanded Access

The main purpose of this study is to evaluate the activity of low dose oral selinexor (KPT-330) and to evaluate the clinical recovery, the viral load, length of hospitalization and the rate of morbidity and mortality in participants with severe COVID-19 compared to placebo. The study had 2 arms and evaluated selinexor 20 mg + standard of care (SoC) and placebo + SoC. As the treatment for COVID-19 is rapidly evolving, the SoC varied over time and across regions of the world.

COVID-19's mechanism to enter the cell is initiated by its interaction with its cellular receptor, the angiotensin-converting enzyme. As a result of this union, a clathrin-mediated endocytosis process begins. This route is one of the therapeutic targets for which available drugs are being investigated in order to treat COVID-19 infection. This is one of the mechanisms blocked by drugs like ruxolitinib and chloroquine. Various drugs approved for clinical use that block the clathrin-mediated endocytosis pathway have been explored. It has been found that the best in vitro and in vivo results were obtained with statins, which also allowed generating a greater potent adaptive immune response. Therefore, statins and specifically simvastatin make it possible to block the entry process used by COVID-19, block inflammation by various mechanisms and increase the adaptive immune response. All of these processes are desirable in patients infected with COVID-19. Statins have been proposed to have beneficial effects in patients infected with MERS-COV, another coronavirus similar to COVID-19, but there have been no randomized studies supporting the use of statins in patients with COVID-19 infection. In this project we propose the combined use of one of these drugs, ruxolitinib with simvastatin, looking for a synergistic effect in the inhibition of viral entry and in the anti-inflammatory effect.

The primary objective is to determine the clinical efficacy of Chloroquine (CQ) in health care workers with moderate to high risk of exposure to COVID-19 in preventing symptomatic COVID-19 infections. Secondary endpoints will explore the efficacy of CQ in preventing any infection as defined by seroconversion to positive anti-COVID antibody status.

Background: COVID-19 is a worldwide pandemic and currently there is no effective therapy or vaccine. SARS-CoV-2, the virus that causes the COVID-19 respiratory infection, appears to be very contagious however all the modes of transmission are unclear. Transmission may occur in up to 25 percent of cases when there are no symptoms (asymptomatic). Before there are any symptoms, droplet spray during speaking may increase transmission from person to person; most of the spray is saliva. Researchers at the NIH would like to test saliva for the virus before symptoms are reported. Additionally, they would like to examine the importance of using masks to prevent transmission. They hope to better understand how COVID-19 is spread among people and how it can be prevented. For this study they would like to collect samples from the nose (nasopharyngeal swab), mouth (spit sample), eye (conjunctival fluid) and blood to test for the virus and if it is contagious. Objectives: To determine if the SARS-CoV-2 virus is present in saliva in asymptomatic individuals who are COVID-19 positive. To determine if using masks can prevent transmission. Eligibility: People ages 18 and older without symptoms or with mild symptoms (e.g., low grade fever, mild malaise, minor sore throat, runny nose, or sneezing) who have been in close contact (e.g. live in the same house) with someone who has tested positive for COVID-19 or people who have tested positive for COVID-19 and have mild (e.g., low grade fever, mild malaise, minor sore throat, runny nose, or sneezing) or no symptoms. Design and Procedures: For screening, interested participants will contact a study team member. The interested participant will be asked to provide documentation of COVID-19 positive status, their symptoms, or their contact to a COVID-19 positive person. Participants will be asked to come to the NIH drive-up COVID-19 testing site or NIH Clinical Center (Bethesda, MD) for 2 or more visits in 15 days for the following procedures: nasal swab for COVID-19 and viral load, verbal symptom assessment, saliva collection, and speaking exercise to capture oral fluid. During this time, participants will also be asked to participate in phone calls with the study staff and to complete questionnaires electronically. Participants will have weekly telephone calls to discuss their symptoms and 2-5 drive-up visits to the NIH within 28 days. If visits are scheduled at the Clinical Center, participants will have the option to participate in providing blood sample(s), a conjunctival swab and 1-2 salivary gland biopsies. If a participant has tested positive, they may be asked to return to the NIH after they have recovered from COVID-19 for additional sampling. The following procedures are part of this research: - Speaking exercise - participants will be asked to read a short script with and without wearing a mask. The droplets they produce while they speak will be collected. - Saliva collection - participants will spit into a cup and have saliva collected from different areas of the mouth. They should not eat 90 minutes before this but drinking water or juice is acceptable. They may have their tongue painted with a sour liquid to increase their saliva. - Nasal swab- participants will have a swab rubbed inside their nose. - Nasopharyngeal swab - participants that are close contacts of COVID-19 positive individual(s) and need a COVID-19 test, will have a swab inserted through the nose to rub the back of their throat. - Questionnaires - participants will complete questionnaires about their symptoms electronically at home. The following procedures are optional for participants to agree to participate in and will be performed in the Clinical Center: - Blood sample(s) - participants will have blood collection via venipuncture. - Conjunctival swab - participants will have the inner lower eyelid wiped with swab. - Minor salivary gland biopsy - participants will have tiny glands in mouth removed. Procedure will be done in the hospital. Participants will be paid up to a total of $300 for the study, based on the number of visits to NIH and the types of procedures performed. Payment will be: $50 on Day 1, Day 15 and at the recovery visit. Participants who agree to the optional conjunctival swab and/or biopsy will be paid $50 for each conjunctival swab (up to 1) and/or $50 for each salivary biopsy (up to 2). If at any time the participants start to have moderate or severe respiratory symptoms, their participation in the study will end and they should seek care with their local provider.

This is a single center, randomized, double-blind, placebo-controlled, exploratory phase II study enrolling 60 patients. We propose the administration of a blinded dose of an investigational product (IP) (clazakizumab or placebo [0.9% saline]) in patients with COVID-19 disease and signs of pulmonary involvement who have not yet required mechanical ventilation and/or extracorporeal membrane oxygenation (ECMO). If a patient progresses to mechanical ventilation and/or ECMO or develops clinical signs of deteriorating COVID-19 disease, and there are no treatment related serious adverse events (SAEs), within the initial 14 day period after the first dose of the IP, at the discretion of the investigator or treating physician, open-label clazakizumab 25mg IV x 1 dose may be administered. A minimum of 24 hours should elapse between the first dose of IP and this dose of open-label clazakizumab. The patient will remain blinded as to the identity of the IP administered in the first dose.

Protection of endothelial dysfunction by intravenous infusion of Defibrotide (Defitelio), expected to decrease inflammation and expression of adhesion molecules in the endothelium, leukocyte tissue infiltration and epithelial destruction, and to promote immune tolerance through a change in the Cytokine balance, which is decisive in preventing multiorgan failure and death in patients with SARS-CoV-2 infection with clinical status grade 4 or 5 according to the WHO classification

This is an exploratory study to evaluate the efficacy of hydroxychloroquine (400 mg BID on D1 and 400 mg/day on D2 to D7) and azithromycin (500 mg/ 5 days) to treat mild ambulatory COVID-19 patients.

This current proposal evaluates the Longitudinal Energy Expenditure and Metabolic Effects in Patients with COVID-19 (LEEP-COVID) to understand, guide and optimize our metabolic and nutritional care of these high risk patients. As no data exist for the metabolic effects of COVID-19 patients, this data is urgently needed and essential to assist in the care of COVID-19 patients worldwide. We are uniquely positioned at Duke to perform this research, as we are the only US center with 2 of the FDA-approved devices in existence currently capable of collecting this vital data to guide the care of COVID-19 patients worldwide.

The project is an observational, prospective study. Its aim is to deepen our understanding of COVID-19 in older patients hospitalized and diagnosed with COVID-19. In particular, socioeconomic, diagnostic, biological, functional, therapy data will be collected at the patients' admission, during hospital stay, at the discharge and 1, 3, 6, 12 months after discharge. Results and findings will help support changes in clinical practice and decision making, with the aim to reduce the use of healthcare services and the healthcare expenditure.

There is currently no treatment available for COVID-19, the acute respiratory illness caused by the novel SAR-CoV-2. Convalescent plasma from patients who have recovered from COVID-19 that contains antibodies to the virus is a potential therapy. On March 25th, 2020, the FDA approved the use of convalescent plasma under the emergency investigational new drug (eIND) category. Randomized trials are needed to determine the efficacy and safety of COVID-19 convalescent plasma for acute COVID-19 infection. The objective of the CONCOR-1 trial is to determine the efficacy of transfusion of COVID-19 convalescent plasma to adult patients admitted to hospital with COVID-19 infection at decreasing the frequency of in-hospital mortality in patients hospitalized for COVID-19. It is hypothesized that treating hospitalized COVID-19 patients with convalescent plasma early in their clinical course will reduce the risk of death, and that other outcomes will be improved including risk of intubation, and length of ICU and hospital stay. This pan-Canadian clinical trial has the potential to improve patient outcomes and reduce the burden on health care resources including reducing the need for ICU beds and ventilators.