COVID-19 Clinical Trials and Expanded Access

This is a Phase 1, open-label, multicenter, dose-escalation, safety, tolerability,pharmacokinetic and pharmacodynamic study with cohort expansion at the RP2D to evaluatesafety and anti- tumor activity of Q702 administered orally.

Viruses are a major health problem for the general public and at risk populations.Normally, detection of antibody titers is the gold standard for determining theeffectiveness of the immune system following natural or vaccine caused immunization.However, determining the effectiveness of other parts of the immune system are lesscommon due to the difficulties with testing. Furthermore, there is a critical need toaddress other therapies in case vaccination is not successful in immuncompromisedpopulations. Exercise has been shown to increase the strength of the immune systemagainst many types of viruses and therefore could be simple way to improve immunityagainst the COVID-19 virus. The aim of this research is to determine the effects ofexercise on anti-viral immunity against many types of common viruses before and aftervaccination. We hypothesize that exercise will enhance the anti-viral immunity before andafter vaccination.Up to 30 healthy volunteers (age 18-44 years) will be recruited to participate in thisstudy. For completion of Aim 1, three visits are needed totaling around 7 hours of thepatient's time and for Aim 2, three visits are needed totaling around 4.5 hours of thepatient's time. The initial visit will be for pre-screening and if deemed healthy enoughto participate, an exercise test to determine the VO2 max of the participant will beconducted. The following visits will require a trained phlebotomist to insert anin-dwelling catheter and participants will undergo a 20-minute incremental exercisetrial. Approximately 50mL of blood will be collected at four different timepoints: atrest, 60% VO2 max, 80% VO2 max, and 1-hr post-exercise. All four collected blood sampleswill be used to expand viral specific T-cells and compare IFN-γ rele

Coronavirus disease 2019 (COVID-19) which is caused by the virus Severe Acute RespiratorySyndrome Coronavirus-2 (SARS-CoV-2) has resulted in an ongoing global pandemic. It isunclear whether the relatively low number of reported cases of COVID-19 in people with CF(pwCF) is due to enhanced infection prevention practices or whether pwCF have protectivegenetic/immune factors. This study aims to prospectively assess the proportion of pwCF,including both adults and children with CF who have evidence of SARS-CoV-2 antibodiesover a two-year period. This study will also examine whether pwCF who have antibodies forSARS-CoV-2 have a different clinical presentation and what impact this has on their CFdisease. The proposed study will recruit pwCF from paediatric and adult CF centresthroughout the United Kingdom. Serological testing to detect antibodies will be performedon blood samples taken at month 0, 6, 12, 18 and 24 with additional time-points ifbloodwork is available via normal clinical care. Clinical data on, lung function,CF-related medical history, pulmonary exacerbations, antibiotic use, and microbiology andvaccination receipt, will be collected during routine clinical assessments.Associations will be examined between socio-demographic and clinical variables andserologic testing. The investigators will also examine the effects of SARS-CoV-2infection on clinical outcomes and analyse end-points to explore any age-related orgender-based differences, as well as subgroup analysis of outcomes in lung-transplantrecipients and pwCF receiving cystic fibrosis transmembrane conductance regulator (CFTR)modulator therapies. As pwCF receive COVID-19 vaccination the investigators will performa comparison of the development and progression of anti-SARS-CoV-2 antibodies in pwCFfollowing natural infection and vaccination SARS-CoV-2 over time.

A Phase 1, Randomized, First-in-human, Open-label Study to Evaluate the Safety andImmunogenicity of eOD-GT8 60mer mRNA Vaccine (mRNA-1644) and Core-g28v2 60mer mRNAVaccine (mRNA-1644v2-Core) in HIV-1 Uninfected Adults in Good General Health

This is an observational COVID-19 study that uses wearable health monitoring technologyto follow COVID-19 positive individuals to monitor persistent symptoms and any potentiallong-term complications or cardiovascular and behavioral impacts from the disease.

The aims of this study are to assess whether the use of a MBI therapy delivered remotelyis associated with a reduction of perceived stress among HCPs in the Radiation MedicineProgram (RMP) and with a decrease risk of burnout during and post COVID-19.

The COVID-RASi study is an international randomized clinical trial that will evaluate thepotential benefit of angiotensin modulators on clinical outcomes, in COVID-19 patients.The purpose of this study is to determine if renin-angiotensin system inhibitors (RASi),with angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers(ARB), has a beneficial effect in patients with COVID-19 infections, by reducing ICUadmission, ventilator requirement or death. We would also like to determine if there aredifferences between ACEi and ARB therapeutic treatments. With the increasing potential oflong COVID symptoms, at the 1 year follow up, a primary endpoint will be the quality oflife of study participants, as assessed by ongoing symptoms and/or the standardizedquestionnaires.

Primary Objective:Primary population (former smokers cohort): - Evaluate the efficacy of itepekimab compared with placebo on the annualized rate of acute moderate-or-severe COPD exacerbations in former smokers with moderate-to-severe COPDSecondary Objectives:Primary population (former smokers cohort): - Evaluate the efficacy of itepekimab compared with placebo on pulmonary function in former smokers with moderate-to-severe COPD - Evaluate the efficacy of itepekimab compared with placebo on occurrence of acute exacerbation of COPD (AECOPD) in former smokers with moderate-to-severe COPD - Evaluate the efficacy of itepekimab compared with placebo on severe AECOPD in former smokers with moderate-to-severe COPD - Evaluate the efficacy of itepekimab compared with placebo on corticosteroid-treated AECOPD in former smokers with moderate-to-severe COPD - Evaluate the efficacy of itepekimab compared with placebo on respiratory symptoms in former smokers with moderate-to-severe COPD - Evaluate the efficacy of itepekimab compared with placebo on Forced Expiratory Volume in 1 second (FEV1) slope in former smokers with moderate-to-severe COPD - Evaluate the efficacy of itepekimab compared with placebo on health-related quality of life (HRQoL) as assessed by St. George's Respiratory Questionnaire (SGRQ) in former smokers with moderate-to-severe COPD - Evaluate the safety and tolerability of itepekimab in former smokers with moderate-to-severe COPD - Evaluate the pharmacokinetic (PK) profile of itepekimab in former smokers with moderate-to-severe COPD - Evaluate immunogenicity to itepekimab in former smokers with moderate-to-severe COPDSecondary population (current smokers cohort) - Estimate the efficacy of itepekimab compared with placebo on the annualized rate of acute moderate or severe COPD exacerbations in current smokers with moderate-to-severe COPD - Estimate the efficacy of itepekimab compared with placebo on pulmonary function in current smokers with moderate-to-severe COPD - Estimate the safety and tolerability of itepekimab in current smokers with moderate-to-severe COPD - Estimate the PK profile of itepekimab in current smokers with moderate to severe COPD - Estimate immunogenicity to itepekimab in current smokers with moderate-to-severe COPD

Preliminary reports have been received from several sources that the periodic inhaling ofthe nebulized mist from water that has a heightened level of kinetic activity has quickly(less than 2 days) lessened the severity of symptoms in Covid-19 infected patients. On atleast several occasions, a repeat PCR test performed several after inhaling a particularwater-based product was negative. There are no perceived adverse effects from inhalingthe water mist by using a nebulizer or humidifier. It is important, however, to validatethese preliminary findings and to include the inhaling of the mist from water, which doesnot have an elevated level of kinetic activity. This will be by performed in apatient-blinded manner by sequentially inhaling the two types of water over consecutive2-day periods with Covid-19 testing at the end of each of the two day periods.Participants will be randomized as to whether they are to inhale the mist from the testor the control water.

A Respiratory infection with the SARS-CoV2 virus is associated with a major risk of viralpneumonia that can lead to respiratory distress requiring resuscitation. In the mostsevere forms, it may require mechanical ventilation or even lead to an acute respiratorydistress syndrome with a particularly poor prognosis. The SARS-CoV2 is a single-strandedRNA virus of positive polarity and belongs to the beta genus of Coronaviruses. SARS-CoV2is responsible for the third epidemic in less than twenty years secondary to aCoronavirus (SARS-CoV then MERS-CoV) and if the mortality associated with it is lowerthan that of previous strains, notably MERS-CoV, its spread is considerably big. As aresult, the number of patients developing respiratory distress requiring invasivemechanical ventilation is high, with prolonged ventilation duration in these situations