COVID-19 Clinical Trials and Expanded Access

This phase 2 trial studies the immune response to GEO-CM04S1 (previously designated asCOH04S1) compared to standard of care (SOC) mRNA SARS-COV-2 vaccine in patients withblood cancer who have received stem cell transplant or cellular therapy.GEO-CM04S1 belongs to a category called modified vaccinia Ankara (MVA) vaccines, createdfrom a new version of MVA, called synthetic MVA. GEO-CM04S1 works by inducing immunity(the ability to recognize and fight against an infection) to SARS-CoV-2. The immunesystem is stimulated to produce antibodies against SARS-CoV-2 that would block the virusfrom entering healthy cells. The immune system also grows new disease fighting T cellsthat can recognize and destroy infected cells. Giving GEO-CM04S1 after cellular therapymay work better in reducing the chances of contracting coronavirus disease 2019(COVID-19) or developing a severe form of COVID-19 disease in patients with blood cancercompared to SOC mRNA SARS-CoV-2 vaccine.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused pandemic sinceoutbreak in 2020.Patients with chronic liver disease (CLD) are at higher risk ofmortality and morbidity due to COVID-19. Despite there is a large number of clinicaltrials of COVID-19 vaccines, only a few participants with chronic liver diseases wereincluded.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused pandemic sinceoutbreak in 2020. Patients with cancers may be at higher risk than those without cancerfor coronavirus disease 2019 (COVID-19). At present, limited data are available on thesafety and immunogenicity of COVID-19 vaccination for patients with cancer.

(a) Objectives 1. To assess the full lung function, exercise capacity, quality of life in patients with COVID-19 over 2 years. 2. To assess the longevity of the serology response to SARS-CoV2. 3. To investigate the association of the neutralization titer in plasma from different vaccinated cohorts to its protection of infection using in vivo model 4. To investigate the SARS-CoV-2 specific cellular and humoral immunities as well as their determinant factors from community subjects who have received different types of COVID-19 vaccines. 5. To assess the third booster dose for subjects who have poor antibody response despite having received two doses of CoronaVac (Sinovac)

This is a phase I trial followed by a phase II randomized trial. The purpose of phase Istudy is the feasibility of treating patients with acute respiratory distress syndrome(ARDS) related to COVID-19 infection (COVID-19) with cord blood-derived mesenchymal stemcells (MSC). The purpose of the phase II trial is to compare the effect of MSC withstandard of care in these patients. MSCs are a type of stem cells that can be taken fromumbilical cord blood and grown into many different cell types that can be used to treatcancer and other diseases. The MSCs being used for infusion in this trial are collectedfrom healthy, unrelated donors and are stored and grown in a laboratory. Giving MSCinfusions may help control the symptoms of COVID-19 related ARDS.

The goal of this project is to rapidly screen promising agents, in the setting of anadaptive platform trial, for treatment of critically ill COVID-19 patients. In this phase2 platform design, agents will be identified with a signal suggesting a big impact onreducing mortality and the need for, as well as duration, of mechanical ventilation.

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.

The overall objective of the study is to evaluate the safety and efficacy of MSC therapycombined with best supportive care in hospitalized patients with COVID-19.

The objective of the COVID-19 Vaccines International Pregnancy Exposure Registry(C-VIPER) is to evaluate obstetric, neonatal, and infant outcomes among women vaccinatedduring pregnancy with a COVID-19 vaccine.Specifically, the C-VIPER will estimate the risk of obstetric outcomes (spontaneousabortion, antenatal bleeding, gestational diabetes, gestational hypertension,intrauterine growth restriction, postpartum hemorrhage, fetal distress, uterine rupture,placenta previa, chorioamnionitis, Caesarean delivery, COVID-19), neonatal outcomes(major congenital malformations, low birth weight, neonatal death, neonatalencephalopathy, neonatal infections, neonatal acute kidney injury, preterm birth,respiratory distress in the newborn, small for gestational age, stillbirth, COVID-19),and infant outcomes (developmental milestones [motor, cognitive, language,social-emotional, and mental health skills], height, weight, failure to thrive, medicalconditions during the first 12 months of life, COVID-19) among pregnant women exposed tosingle (homologous) or mixed (heterologous) COVID-19 vaccine brand series from 30 daysprior to the first day of the last menstrual period to end of pregnancy and theiroffspring relative to a matched reference group who received no COVID-19 vaccines duringpregnancy.

The ongoing Coronavirus Disease 2019 (COVID-19) pandemic has been intensified by nopopulation-based immunity to the severe acute respiratory disease coronavirus 2(SARS-CoV2) and initially lack of effective treatments or vaccines available to mitigatethe pandemic. Currently, two COVID-19 vaccines are available for vaccination in Europethrough conditional marketing authorisation granted by the European Medicines Agency andfurther vaccine will be licensed. These vaccines have shown good vaccine efficacy inphase 3 vaccine trials. We will recruit subjects who will be prioritised for vaccinationwith the primary aim of comparing the immune responses after COVID-19 vaccination andnatural SARS-CoV-2 infection. In Western Norway we have recruited cohorts of health careworkers and patients infected with SARS-CoV-2 and will extend to COVID-19 vaccinees.Demographic, clinical data and repeated blood samples will be collected to evaluate thecomplications and kinetics, duration and breadth of the immune responses comparingnatural infection to vaccination.