COVID-19 Clinical Trials and Expanded Access

This is a first-in-human, phase I/IIa, randomized, controlled, observer-blinded, dose-escalation, multicentre clinical trial to evaluate safety and immunogenicity of COVID-19 HIPRA vaccine in adult healthy volunteers.

This is a randomized, double-blind, placebo-controlled study of RP7214 in patients with symptomatic mild SARS-CoV-2 infection, having at least one high-risk feature (e.g., age > 60 years, hypertension, diabetes mellitus, chronic lung disease, chronic kidney disease, liver disease, cerebrovascular disease, obesity, cancer) for developing severe Covid-19 illness.

This study will test the COVID-19 vaccine candidate AZD1222 to investigate its safety, tolerability and capability of boosting immune responses both in the blood and the lung when administered to the respiratory tract, in volunteers previously vaccinated by intramuscular COVID-19 vaccination. Using standardised methods, we will measure immune responses in the blood, nose and lower airway and compare with data from ongoing clinical trials of intramuscular vaccination. Thus, we will show the effect of the delivery method and provide the critical information required to begin further clinical trials to show the efficacy of this needle-free vaccination strategy for booster vaccination.

The global COVID-19 pandemic has caused unprecedented strain on health care services around the world.The absence of specific anti-viral medications to treat the underlying infection led to a proliferation of clinical studies and trials aimed at re-purposing existing medications. Human dihydroorotate dehydrogenase (DHODH) is vital enzyme utilised by viruses to replicate in the host cell. Leflunomide, a drug that is already licenced to treat rheumatoid arthritis, is a potent inhibitor of the enzyme DHODH. Importantly, this drug has dual anti-viral and anti-inflammatory properties so it targets viral replication and suppresses host inflammatory response which plays a role at more progressive stages of infection. DEFEAT-COVID is a multi-site, international, interventional, pragmatic, parallel group design, open label, randomised CTIMP with a pilot phase that will allow to adapt procedures and assessments if required. A phase III clinical trial of leflunomide for treating COVID-19 has been registered in China, Registration number: ChiCTR2000030058). The current proposal extends the original clinical study of leflunomide in China (People's Hospital of Wuhan University) to the UK through a structured collaboration.

The purpose of this study is to evaluate the safety and effectiveness of ketotifen and indomethacin taken together to improve symptoms related with COVID-19. Ketotifen and indomethacin are medications approved by the Food and Drug Administration (FDA) to treat diseases other than COVID-19. Their use in this study is investigational, meaning they have not been approved by the FDA to treat COVID-19.

In recent months, more and more studies suggest tele-rehabilitation as a means to be exploited to reduce the risk of contagion. The intent of our study is to verify the effectiveness of a tele-rehabilitation intervention through the application of a respiratory rehabilitation program supported by contact with physiotherapists, in patients with outcomes from SARS-CoV-2 infection discharged from the various medical departments and taken over by physiotherapists after physiatric evaluation. Faced with the same rehabilitation program prescribed to all patients, the primary objective of our study is to detect whether patients supported by remote rehabilitation after hospitalization improve both adherence to the rehabilitation program and cardiorespiratory endurance and dyspnea symptoms assessed with the Six Minute Walking Test scale (6MWT). This test is validated for multiple pathologies, including idiopathic pulmonary fibrosis, the clinic of which could be comparable to the outcomes of coronavirus interstitial pneumonia as suggested by the literature. The secondary objectives concern the assessment of the impact of physical exercise assisted by tele-rehabilitation detected through: the assessment of the quality of life (Saint George Respiratory Questionnaire );the assessment of autonomy in daily life activities (Barthel Index Dyspnea Scale), the evaluation of the variation in thoracic expansion and lung volumes (with COACH , an instrument for respiratory physiotherapy that measures the inspiratory volume in ml); the evaluation of muscle strength and endurance (One Minute Sit To Stand) ; the detection of dyspnea during the execution of the exercises (Modified Borg scale); the assessment of the functionality of the lower limbs (Short Physical Performance Battery)

On 11 February 2020, the International Committee for the Classification of Viruses named the disease caused by SAＲS-CoV-2 infection in humans as the new coronavirus pneumonia (coronavirus disease 2019, COVID-19). Due to the characteristics of liver microcirculation disturbance and immune function disorder in patients with chronic liver diseases (such as immune liver disease, chronic hepatitis C, liver cirrhosis, liver cancer, etc.), those patients has a higher risk of infection than the general population during the epidemic period. More attention should be paid to personal protection and disease prevention. Vaccination of COVID-19 vaccine can effectively prevent COVID-19 virus infection and delay or prevent patients from developing into critical illness and reduce mortality. To evaluate the safety and effectiveness of COVID-19 vaccine in those patients with chronic liver diseases, and to guide the COVID-19 vaccination more scientifically, reasonably and effectively, this study was carried out.

This trial consists of three parts, Part A, Part B, and Part C, and will evaluate the safety and immunogenicity of a third booster injection of the multivalent vaccine BNT162b2 (B.1.1.7 + B.1.617.2), and the safety and immunogenicity of a third booster injection of the monovalent vaccine BNT162b2 (B.1.617.2) or BNT162b2 (B.1.1.7), in participants who have received two doses of the parent vaccine BNT162b2 at 30 µg, at least 6 months after the second dose of BNT162b2. It will also evaluate the safety and immunogenicity of a three-dose regimen of BNT162b2 (B.1.1.7 + B.1.617.2) in participants who have not received prior Coronavirus Disease 2019 (COVID-19) vaccination. In addition, the safety and immunogenicity of BNT162b2 (B.1.1.529) or BNT162b2 given as a third or fourth vaccine dose to RNA COVID-19 vaccine-experienced participants with history of SARS-CoV-2 infection will be evaluated and contrasted with the natural immune response reached after infection with the SARS-CoV-2 Omicron variant.

A randomized, double-blind, placebo -controlled, phase IIb clinical trial to evaluate the efficacy, safety and immunogenicity of one or two doses of Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) in adults 18 years of age and older, living with HIV, on stable treatment, and virologically suppressed for at least 6 months Protocol number: FH-58

This will be a prospective observational study of lactating mothers who are planning to, have scheduled or have received vaccination against SARS-COV-2 (COVID-19 vaccine). Mothers may have delivered at Mount Sinai Hospital or may be from the general public recruited by social media or word of mouth. As the study participants will be lactating mothers, they will not be under the care of the investigators. Due to lack of information, we are unsure of an appropriate sample size but envision we will recruit at least 10 women each immunized with the approved mRNA vaccines (e.g. Pfizer-BioNTech and Moderna COVID-19 vaccines) and in the future at least two other vaccines (e.g. Oxford-AstraZeneca) as they are approved and become available. Milk samples will be analyzed for the presence of antibody to SARS-CoV-2 using the Anti-SARS-CoV-2 ELISA (IgG and IgA). These analyses will be conducted in the Department of Microbiology at Sinai Health following validation of the procedures in human milk.