NCT05041907

Finding Treatments for COVID-19: A Trial of Antiviral Pharmacodynamics in Early Symptomatic COVID-19 (PLATCOV)

Finding Treatments for COVID-19: A Phase 2 Multi-centre Adaptive Platform Trial to Assess Antiviral Pharmacodynamics in Early Symptomatic COVID-19 (PLATCOV)

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 3,800 (estimated)
• Sponsor: University of Oxford · Academic / Other
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Not accepted

Summary

The trial will develop and validate a platform for quantitative assessment of antiviral effects in low-risk patients with high viral burdens and uncomplicated COVID-19 to determine in-vivo antiviral activity. In this randomized open label, controlled, group sequential adaptive platform trial, we will assess the performance of three distinct types of intervention relative to control (no treatment): A: Small molecule drugs; B: Monoclonal antibodies; C: Dose finding for the constituent parts of nirmatrelvir/ritonavir PLATCOV study is supported by the Wellcome Trust Grant ref: 223195/Z/21/Z through the COVID-19 Therapeutics Accelerator.

Detailed description

The platform trial will assess drugs with potential SARS-CoV-2 antiviral activity of three general types: A. Small molecule drugs: currently nitazoxanide, nirmatrelvir/ritonavir, hydroxychloroquine, atilotrelvir/ritonavir and metformin. B. Monoclonal antibodies: Sotrovimab and any other monoclonal antibodies that become available. Monoclonal antibodies are vulnerable to viral escape mutations. Tracking their performance over time is important to characterise the impact and inform the therapeutics of mutant SARS-CoV-2 strains. This will also be important for other antivirals. Monoclonal antibodies are expensive and cannot be produced at large scale currently, but this may change in the near future. These drugs will be included if there is local availability and regulatory approval. C. : Dose finding for the constituent parts of nirmatrelvir/ritonavir. Nirmatrelvir/ritonavir has shown clinical efficacy in phase III studies, however, there are disadvantages to using it (drug-drug interactions, side effects, cost). In the urgent context of the pandemic, a higher dose of ritonavir was chosen to guarantee maximum boosting effect. We do not know if the maximal boosting effect could have been achieved with less, or even without ritonavir. It will be investigated whether reducing the doses of the constituent parts can still retain the effectiveness. Randomization to the no antiviral treatment control arm (no intervention) will be fixed at a minimum of 20% throughout the study. The randomization ratios will be uniform for all available interventions. Recruitment into the ivermectin arm was stopped on April 18th 2022 due to meeting the pre- defined stopping criteria. Recruitment into the remdesivir arm was stopped on June 10th 2022 due to meeting the pre- defined stopping criteria. Recruitment into the REGN-COV2 arm was stopped on October 20th 2022 due to meeting the pre-defined stopping criteria. Recruitment into the favipiravir arm was stopped on October 31st 2022 due to meeting the pre-defined stopping criteria. Recruitment into the molnupiravir arm was stopped on February 22nd 2023 due to meeting the pre-defined stopping criteria. Recruitment into the fluoxetine arm was stopped on May 8th 2023 due to meeting the pre-defined stopping criteria. Recruitment into the evusheld arm was stopped on July 4th 2023 due to meeting the pre-defined stopping criteria. Recruitment into the ensitrelvir arm was stopped on April 21st 2024 due to meeting the pre-defined stopping criteria. Recruitment into the combination molnupiravir and nirmatrelvir/ritonavir (e.g. PAXLOVID™) arm was stopped on May 31st 2024 due to meeting the pre-defined stopping criteria.

Conditions

• COVID-19

Interventions

Type	Name	Description
DRUG	Nirmatrelvir/ritonavir (e.g. PAXLOVID™)	Nirmatrelvir 300mg BD for 5/7 Ritonavir 100mg BD for 5/7
DRUG	Nitazoxanide	Nitazoxanide 1.5g BD 7/7
DRUG	Molnupiravir and nirmatrelvir/ritonavir (e.g. PAXLOVID™)	Molnupiravir 800mg BD for 5/7, Nirmatrelvir 300mg BD for 5/7, Ritonavir 100mg BD for 5/7
DRUG	Hydroxychloroquine	Hydroxychloroquine 400mg D0 BD and 400MG OD for a further 6/7
OTHER	No treatment	No treatment (except antipyretics- paracetamol)
DRUG	Monoclonal antibodies	Monoclonal antibodies: 300mg tixagevimab/ 300 mg cilgavimab given once on D0
DRUG	Fluoxetine	Fluoxetine 40mg OD for 7/7
DRUG	Molnupiravir	Molnupiravir 800mg BD for 5/7
DRUG	Sotrovimab	Sotrovimab 500mg given once on D0
DRUG	Ensitrelvir	Ensitrelvir 375mg OD D0 and 125mg OD for a further 4/7
DRUG	Monoclonal antibodies	Monoclonal antibodies: 600mg casirivimab/ 600mg imdevimab given once on D0
DRUG	Favipiravir	Favipiravir 1800mg BD D0 and 800mg BD for a further 6/7
DRUG	Ivermectin	Ivermectin 600micrograms/kg/day for 7/7.
DRUG	Remdesivir	Remdesivir 200mg D0 and 100mg for a further 4/7.
DRUG	Atilotrelvir/ritonavir	Atilotrelvir 150mg BD for 5/7 Ritonavir 100mg BD for 5/7
DRUG	Metformin	Metformin 500mg TDS 5/7
DRUG	Nirmatrelvir/ritonavir	Nirmatrelvir 300mg BD for 5/7 Ritonavir 50mg BD for 5/7
DRUG	Nirmatrelvir/ritonavir	Nirmatrelvir 150mg BD for 5/7 Ritonavir 50mg BD for 5/7
DRUG	Nirmatrelvir	Nirmatrelvir 300mg BD for 5/7

Timeline

• Start date: 2021-09-30
• Primary completion: 2027-01-01
• Completion: 2027-01-01
• First posted: 2021-09-13
• Last updated: 2026-02-19

Locations

7 sites across 5 countries: Brazil, Laos, Nepal, Pakistan, Thailand