PROphylaxis for paTiEnts at Risk of COVID-19 infecTion -V
brief summary
COVID-19 (SARS-CoV2 virus) was declared a global pandemic by the WHO on 11th March 2020. Currently there are no drugs proven to prevent COVID-19 or to reduce the severity of illness if given as prophylaxis. Although vaccines are now available, there remains a need for other prophylactic agents until vaccine use becomes widespread globally and effectiveness and durability is established, particularly in immunocompromised individuals, for whom vaccine responses may be suboptimal. Efforts are underway to repurpose established drugs with well understood drug interactions and safety profiles. PROTECT-V is a platform trial to test prophylactic interventions against SARS-CoV2 infection in vulnerable patient populations at particularly high risk of COVID-19 and its complications, seeking to identify treatments that either might prevent the disease from occurring or may reduce the number of cases where the disease becomes serious or life-threatening. In PROTECT-V, multiple agents can be evaluated on the same platform across vulnerable populations, with the option of adding additional treatments at later time points as these become available. The expectation is for as many sites as possible to recruit to all available trial treatments at any time, however, the platform structure and randomisation/data collection systems allow sites to open the trial treatment arms according to their capacity. The trial opened with intranasal niclosamide and matched placebo, aiming to recruit 1500 vulnerable renal patients in February 2021. A parallel study protocol, was conducted in India, sponsored by The George Institute. Recruitment of around 750 Indian patients was completed in with the rest of the study arm recruitment in November 2022. The Niclosamide arm of the study was completed in June 2023. The second agent, intranasal and inhaled ciclesonide and matched placebo, was meant to be added to the platform in mid-2022 in the same renal patient population however it was unable to be included due to other factor. Sotrovimab and matched placebo have been added to the platform in August 2022 which aim to recruit approximately 800-1000 patients from the main study population with additional patient groups with primary immunodeficiency, any Haematology or Oncology patient who is currently receiving or has received chemotherapy or who is immunocompromised as a result of their disease or treatment, those with a diagnosis of an autoimmune or inflammatory disease receiving immunosuppression and also haematopoietic stem cell transplant recipients.
detailed description
Part 1: Inhaled repurposed agents The trial commenced with the first intervention, nasal niclosamide and matched placebo from February 2021. The intended second intervention is nasal and inhaled ciclesonide. Participants are being randomised in a 1:1 ratio until the second intervention is introduced. Once ciclesonide is introduced, participants who are eligible for ciclesonide will be randomised to niclosamide, ciclesonide, niclosamide matching placebo or ciclesonide matching placebo in a 2:2:1:1 ratio. The net result will be a 1:1:1 distribution between niclosamide, ciclesonide and placebo, with niclosamide-matching placebo and ciclesonide-matching placebo pooled for the analysis.
Three vulnerable patient populations were enrolled initially: dialysis patients, kidney transplant recipients and those with vasculitis or other auto-immune kidney disease such as systemic lupus erythematosus (SLE) or glomerulonephritis (GN) These patient groups are noted to be particularly vulnerable to COVID-19 infection by virtue of demographics, underlying co-morbidities or as a consequence of treatments for these conditions, and they are at exceptionally high risk of adverse outcomes. Additionally these groups are known to mount sub-optimal responses to vaccination.
Approximately 1500 participants will be randomised to active treatment or placebo, stratified by PROTECT sub-population, age and participating sites. Enrolment to the trial will be via an online platform following informed consent with a face to face screening visit. The screening visit will include assessment of eligibility (which will include liver function tests and COVID-19 PCR test), randomisation, baseline data collection and research serum sample collection to detect anti SARS-COV-2 antibodies. Subsequent assessments, aside from an in person end of trial visit, will be done via email or telephone together with utilising the routine collected health data thus reducing the burden to participants as well as reducing their exposure to COVID-19. Telephone consultations will be carried out at weeks 1, 2, 3, 4 and 6, followed by two weekly self-reporting at week 8 onwards.
If a participant has not submitted data for a period of approximately 6 weeks, they will be contacted by the local study team for a telephone interview to minimise loss to follow up. Failure to follow up a participant for more than 6 consecutive weeks will halt their trial treatment dispensation until communication has been restored. Failure to follow up a participant for more than 12 consecutive weeks will be considered loss of follow up and conclude their participation in the trial.
If a participant develops symptoms suggestive of COVID-19 infection they should arrange an urgent COVID-19 test. They should notify their trial physician. Participants should continue taking trial medication (if self-administering medication) until advised to stop by a member of the trial team or admitted to hospital. Any participant testing positive for SARS-CoV-2 will be required to complete a COVID-19 symptom assessment at least weekly for 4 weeks after diagnosis, unless hospitalised.
official title
PROphylaxis for paTiEnts at Risk of COVID-19 infecTion