COVID-19 Clinical Trials and Expanded Access

The purpose of this study is to test whether Fisetin, a senolytic drug, can assist inpreventing an increase in the disease's progression and alleviate complications ofcoronavirus due to an excessive inflammatory reaction.

COVID-19 is a community acquired pneumonia caused by infection with a novel coronavirus,SARS CoV2 and is a serious condition with high mortality in hospitalised patients, forwhich there is no currently approved treatment other than supportive care. Urgentinvestigation of potential treatments for this condition is required.This protocol describes an overarching and adaptive trial designed to provide safety,pharmacokinetic (PK)/ pharmacodynamic (PD) information and exploratory biologicalsurrogates of efficacy which may support further development and deployment of candidatetherapies in larger scale trials of COVID-19 positive patients receiving normal standardof care.Given the spectrum of clinical disease, community based infected patients or hospitalisedpatients can be included. Products requiring parenteral administration will only beinvestigated in hospitalised patients. Patients will be divided into cohorts, a)community b) hospitalised patients with new changes on a chest x-ray (CXR) or a computedtomography (CT) scan or requiring supplemental oxygen and c) hospitalised requiringassisted ventilation. Participants may be recruited from all three of these cohorts,depending on the experimental therapy, its route of administration and mechanism ofaction. The relevant cohort(s) for any given therapy will be detailed in thetherapy-specific appendix.Candidate therapies can be added to the protocol and previous candidates removed fromfurther investigation as evidence emerges. The trial will be monitored by an independentData Monitoring Committee (DMC) to ensure patient safety.Each candidate cohort will include a small cohort of patients randomised to candidatetherapy or existing standard of care management dependent on disease stage at entry.Cohort numbers will be defined in the protocol appendices.This is a Phase IIa experimental medicine trial and as such formal sample sizecalculations are not appropriate.

This Phase 2 Randomized Placebo Controlled Trial will determine if administeringnebulized Dornase Alpha (rhDNase) to COVID-19 patients with respiratory failure is safeand will reduce 28-day mortality.

The objectives of this intermediate-size expanded access protocol are to assess thesafety and efficacy of remestemcel-L in participants with MIS-C associated with COVID-19.

In this study we cross-reference several nationwide high-quality Swedish registers inorder to study risk factors for severe Covid-19 outcomes.

Thymalfasin (thymosin alpha 1 or Ta1), the active pharmaceutical ingredient in ZADAXIN®injection, is a 28-amino acid synthetic peptide, identical to natural Ta1 produced by thethymus gland. Ta1 is a biological response modifier which activates various cells of theimmune system, and is therefore expected to have clinical benefits in disorders whereimmune responses are impaired or ineffective, including acute and chronic viral andbacterial infections, cancers, and vaccine non-responsiveness. Patients with end-stagerenal disease (ESRD) on hemodialysis, in addition to their intrinsic kidney disease andfrequent burden of comorbidities, also have increased risk of exposure to communicablediseases as they are treated several times each week at hemodialysis centers with severalother patients and clinic staff in attendance. The majority of patients are over 60 yearsof age and many are receiving immunosuppressive medications. Accordingly, ESRD patientsare particularly susceptible to COVID-19 infection. Ta1 has been shown to be safelyadministered to hemodialysis patients. It is our hypothesis that a course of Ta1administered to individuals with ESRD will reduce the rate and severity of infection withCOVID-19.

Patients suffering lung failure, possibly from COVID-19 or hypoxic lung failure, willneed life-saving support from a breathing machine. Any patient needing this supportrequires drugs to keep them sleepy, or "sedated" to be comfortable on this machine.Sedation is made possible by using drugs given through a vein. Unfortunately, these drugsare in short supply worldwide due to the high number of COVID-19 patients needing thesemachines.Another way to provide sleep is by using gases that are breathed in. These are used everyday in operating rooms to perform surgery. These gases, also called "inhaled agents" canalso be used in intensive care units and may have several important benefits for patientsand the hospital. Research shows they may reduce swelling in the lung and increase oxygenlevels, which allows patients to recover faster and reduce the time spent on a breathingmachine. In turn, this allows the breathing machine to be used again for the next sickpatient. These drugs may also increase the number of patients who live through theirillness. Inhaled agents are widely available and their use could dramatically lesson thepressure on limited drug supplies.This research is a study being carried out in a number of hospitals that will compare howwell patients recover from these illnesses depending on which type of sedation drug theyreceive. The plan is to evaluate the number who survive, their time spent on a breathingmachine and time in the hospital. This study may show immediate benefits and may providea cost effective and practical solution to the current challenges caring for patients andthe hospital space, equipment and drugs to the greatest benefit. Furthermore, the studywill be investigating inflammatory profile and neuro-cognitive profiles in ventilatedpatients. Finally, this trial will be a team of experts in sedation drugs who care forpatients with proven or suspected COVID-19 who need lifesaving treatments.

The purpose of this study is to evaluate pulmonary function of patients recovering frommild, moderate, and severe COVID-19 disease using hyperpolarized 129Xe MRI.

This expanded access protocol will provide access to the investigational product Zofinfor patients in outpatient facilities infected with SARS-CoV-2 who have mild to moderateCOVID-19, or who are judged by a healthcare provider to be at high risk of progression tomoderate disease.

Researchers are creating real-time epidemiology registry to evaluate the efficacy ofCOVID-19 subject risk assessment scores based on recording of symptoms, biomarkers,chronic illness and mental health assessments with digital technology using wearables andmobile app tools. Researchers aim to study in Phase 1, epidemiological variations inCOVID-19 presentation in both PCR positive and negative subjects in the registry.Assessment of variables, predictive modeling of variables that impact severity ofCOVID-19 positive and negative subjects and assessment of predictors for post COVID-19complications. In Phase 2, 2700 subjects with COVID-19 positive test will be studied inthe intervention group comparing ECL-19 vs placebo with primary end point of hospitaladmission assessment. Treatment strategy for PCR positive COVID-19 subjects in theregistry who are in Stage I of the disease process with ECL-19 drug compared to placeboin reducing hospital admissions