Finding treatments for COVID-19: A phase 2 multi-centre adaptive platform trial to assess antiviral pharmacodynamics in early symptomatic COVID-19 (PLATCOV)

Funders:
Wellcome Trust

Trial sites:
Thailand
Nepal
Brazil
Laos

Co-Principal Investigators:

Dr William Schilling
Mahidol Oxford Tropical Medicine Research Unit,
Faculty of Tropical Medicine, Mahidol University

Prof. Sir Nicholas J White
Mahidol Oxford Tropical Medicine Research Unit,
Faculty of Tropical Medicine, Mahidol University

Co-Investigators:

Associate Professor Abhilasha Karkey
Microbiologist
Director, Oxford University Clinical Research Unit Nepal

Associate Professor Buddha Basnyat
Chairperson, Oxford University Clinical Research Unit Nepal

Dr Yuba Nidhi Basaula
Consultant paediatrician
Director, Sukraraj Tropical and Infectious Disease Hospital (STIDH)

Dr Bimal Sharma Chalise
Consultant physician, Sukraraj Tropical and Infectious Disease Hospital (STIDH)

Dr Sulochana Manandhar
Molecular Microbiologist
Oxford University Clinical Research Unit Nepal

Dr Suchita Shrestha
Head of CTU
Oxford University Clinical Research Unit Nepal

Others involved in the project
Shristi Singh
Project Manager
Oxford University Clinical Research Unit Nepal

Alisha Pradhan
Research Coordinator
Oxford University Clinical Research Unit Nepal

Januka Khatri
Clinical Pharmacist
Oxford University Clinical Research Unit Nepal

This study is a randomised, open label, controlled adaptive platform trial that will be conducted in low-risk patients with COVID-19, recruited from outpatient COVID-19/ Acute Respiratory Infection (ARI) clinics or through other approved facilities. Previously healthy patients 18 to 60 years old with early symptomatic COVID-19 and without co-morbidities are eligible for the study. Enrolled patients are followed up daily for 7 days and then on Day 10 and Day 14. Phone follow-up is conducted on Day 28 and Day 120. The interventions in this study currently includes Nitazoxanide, Paxlovid (Nirmatrelvir/Ritonavir), Metformin and Atelotrelvir/Ritonavir.

Background

There are many potential therapeutics for COVID-19 and a much larger number of vaccines are in development. However, there is widespread vaccine inequality. As of 31 December 2023, the WHO states that only 44% of the total global population have been vaccinated against COVID-19. The rapid evolution of more transmissible and potentially vaccine resistant mutant strains (highlighted by the Omicron variant (B.1.1.529), and future variants (which may not be as comparatively mild) is concerning. We know that vaccine and disease-induced immunity is imperfect and short-lived so identifying active antiviral drugs is extremely important. There will always be people, due to their age, comorbidities or being immunocompromised that will need early antiviral therapy. For all these reasons effective therapeutics are needed urgently.

Primary Objectives:

To evaluate SARS-CoV-2 antiviral efficacy in-vivo (accelerated viral clearance relative to the no study drug arm). This is a superiority comparison.
To compare SARS-CoV-2 antiviral efficacy with current best antiviral treatment option (accelerated viral clearance relative to the positive control arm). This is a non-inferiority or superiority comparison.

Secondary Objectives:

To characterise the determinants of viral kinetics in early COVID-19 disease.
To determine optimal dosing regimens through pharmacometric assessment for antiviral drugs with evidence of efficacy (e.g. Nirmatrelvir/ritonavir, etc)
Characterise viral rebound of studied treatment arms in comparison to contemporaneous controls (e.g. no study drug arm, positive control)
To compare rates of fever clearance and rates of symptom resolution with respect to no treatment

Tertiary Objectives

Characterise the relationship between viral clearance and hospitalisation (hospitalisation for clinical reasons)
Characterise the relationship between viral clearance, randomisation arm and other measures (covariates)and development of post-acute COVID-19 (i.e. long COVID)