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

February 16, 2026 updated by: University of Oxford

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

3800

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Brazil
      • Minas Gerais, Brazil
        • Recruiting
        • Universidade Federal De Minas Gerais
        • Contact:
  • Laos
      • Vientiane, Laos, 01000
        • Recruiting
        • Laos-Oxford-Mahosot Wellcome Trust Research unit
        • Contact:
        • Contact:
          • Elizabeth Ashley, Professor
          • Phone Number: (+85)621 250 752
          • Email: liz@tropmedres.ac
  • Nepal
      • Kathmandu, Nepal
        • Recruiting
        • Sukraraj Tropical & Infectious Disease Hospital
        • Contact:
  • Pakistan
      • Karachi, Pakistan
        • Terminated
        • The Aga Khan University Hospital
  • Thailand
      • Bangkok, Thailand, 10400
        • Recruiting
        • Faculty of Tropical Medicine, Mahidol University
        • Contact:
      • Bangkok, Thailand, 10300
        • Terminated
        • Vajira Hospital
      • Mueang Samut Prakan, Thailand, 10540
        • Terminated
        • Bangplee Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patient understands the procedures and requirements and is willing and able to give informed consent for full participation in the study.
  • Previously healthy adults, male or female, aged 18 to 60 years at time of consent with early symptomatic COVID-19
  • SARS-CoV-2 positive by lateral flow antigen test OR a positive PCR test for SARS-CoV-2 within the last 24hrs with a Ct value of less than 25 (all viral targets)
  • Symptoms of COVID-19 (including fever, or history of fever) for less than 4 days (96 hours).
  • Oxygen saturation ≥96% measured by pulse-oximetry at time of screening.
  • Able to walk unaided and unimpeded in ADLs
  • Agrees and is able to adhere to all study procedures, including availability and contact information for follow-up visits

Exclusion Criteria:

The patient may not enter the study if ANY of the following apply:

  • Taking any concomitant medications or drugs (see appendix 4)†
  • Presence of any chronic illness/ condition requiring long term treatment, or other significant comorbidity (e.g. diabetes, obesity but see appendix 4 for the full list)
  • Laboratory abnormalities discovered at screening (see appendix 4)
  • For females: pregnancy, actively trying to become pregnant, or lactation
  • Contraindication to taking, or known hypersensitivity reaction to any of the proposed therapeutics (see appendix 4)
  • Currently participating in another COVID-19 therapeutic or vaccine trial

  • Evidence of pneumonia (although imaging is NOT required)

    • healthy women on the oral contraceptive pill are eligible to join the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Hydroxychloroquine
Drug: Hydroxychloroquine
Hydroxychloroquine 400mg D0 BD and 400MG OD for a further 6/7
Other: Negative control group
Other: No treatment
No treatment (except antipyretics- paracetamol)
Experimental: Nitazoxanide
Drug: Nitazoxanide
Nitazoxanide 1.5g BD 7/7
Active Comparator: Positive control: Nirmatrelvir/ritonavir (e.g. PAXLOVID™)
Drug: Nirmatrelvir/ritonavir (e.g. PAXLOVID™)
Nirmatrelvir 300mg BD for 5/7 Ritonavir 100mg BD for 5/7
Experimental: Sotrovimab [Pending addition]
Drug: Sotrovimab
Sotrovimab 500mg given once on D0
Active Comparator: Positive control (REGN-COV2) [This arm is now closed to recruitment]
Drug: Monoclonal antibodies
Monoclonal antibodies: 600mg casirivimab/ 600mg imdevimab given once on D0
Drug: Monoclonal antibodies
Monoclonal antibodies: 300mg tixagevimab/ 300 mg cilgavimab given once on D0
Experimental: Favipiravir [This arm is now closed to recruitment]
Drug: Favipiravir
Favipiravir 1800mg BD D0 and 800mg BD for a further 6/7
Experimental: Ivermectin [This arm is now closed to recruitment]
Drug: Ivermectin
Ivermectin 600micrograms/kg/day for 7/7.
Experimental: Remdesivir [This arm is now closed to recruitment]
Drug: Remdesivir
Remdesivir 200mg D0 and 100mg for a further 4/7.
Experimental: AZD7442 (EVUSHELD™) [This arm is now closed to recruitment]
Drug: Monoclonal antibodies
Monoclonal antibodies: 600mg casirivimab/ 600mg imdevimab given once on D0
Drug: Monoclonal antibodies
Monoclonal antibodies: 300mg tixagevimab/ 300 mg cilgavimab given once on D0
Experimental: Fluoxetine [This arm is now closed to recruitment]
Drug: Fluoxetine
Fluoxetine 40mg OD for 7/7
Experimental: Molnupiravir [This arm is now closed to recruitment]
Drug: Molnupiravir
Molnupiravir 800mg BD for 5/7
Experimental: Ensitrelvir [This arm is now closed to recruitment]
Drug: Ensitrelvir
Ensitrelvir 375mg OD D0 and 125mg OD for a further 4/7
Experimental: Molnupiravir and Nirmatrelvir/ritonavir (e.g. PAXLOVID™) [This arm is now closed to recruitment]
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
Experimental: Atilotrelvir/ritonavir [Pending addition]
Drug: Atilotrelvir/ritonavir
Atilotrelvir 150mg BD for 5/7 Ritonavir 100mg BD for 5/7
Experimental: Metformin (modified release) [Pending addition]
Drug: Metformin
Metformin 500mg TDS 5/7
Experimental: Nirmatrelvir/ritonavir - 300/50 - dose finding [Pending addition]
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
Experimental: Nirmatrelvir/ritonavir - 150/50 - dose finding [Pending addition]
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
Experimental: Nirmatrelvir - dose finding [Pending addition]
Drug: Nirmatrelvir
Nirmatrelvir 300mg BD for 5/7

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of viral clearance for interventions relative to the no study arm (This is a superiority comparison)
Time Frame: Days 0-5
Rate of viral clearance- estimated from the log10 viral density derived from qPCR of standardised duplicate oropharyngeal swabs/ saliva taken daily from baseline (day 0) to day 5 for each intervention compared with the no antiviral treatment control i.e., those not receiving study drug
Days 0-5
Rate of viral clearance for interventions relative to the positive control arm (This is a non-inferiority or superiority comparison).
Time Frame: Days 0-5
Rate of viral clearance- estimated from the log10 viral density derived from qPCR of standardised duplicate oropharyngeal swabs/ saliva taken daily from baseline (day 0) to day 5 for interventions compared with the current best antiviral treatment option (accelerated viral clearance relative to the positive control arm)
Days 0-5

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Viral kinetic levels in early COVID-19 disease
Time Frame: Days 0-5
Rate of viral clearance estimated from the log10 viral density derived from qPCR of standardised duplicate oropharyngeal swabs/ saliva taken daily from baseline (day 0) to day 5 for each therapeutic arm compared with the no antiviral treatment control i.e., those not receiving study drug
Days 0-5
Optimal dosing regimens through pharmacometric assessment for antiviral drugs with evidence of efficacy in the literature or from the trial data (e.g., Nirmatrelvir/ritonavir, Ensitrelvir etc).
Time Frame: Days 0-5
Rate of viral clearance- estimated from the log10 viral density derived from qPCR of standardised duplicate oropharyngeal swabs/ saliva taken daily from baseline (day 0) to day 5 for each therapeutic arm compared with the no antiviral treatment control i.e., those not receiving study drug
Days 0-5
Viral rebound of studied treatment arms in comparison to contemporaneous controls (e.g. no study drug arm, positive control)
Time Frame: Days 6-14
After stopping treatment for at least 24 hours (or 5 days if no drug is given or a single dose monoclonal antibody is given), rebound is defined as an oropharyngeal eluate viral density estimate >1000 genomes per ml for at least 1 timepoint (average 2 swabs), after >2 consecutive days of average daily viral density estimate less than 100 genomes per ml
Days 6-14
Rates of fever clearance and symptom resolution with respect to no treatment
Time Frame: Days 0-14

The following endpoints will be used:

  • Time to resolution of fever
  • Area Under the Curve of recorded temperature
  • Time to resolution of symptoms
Days 0-14

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rates of hospitalisation by treatment arm (hospitalisation for clinical reasons)
Time Frame: Days 0-28
Number of hospitalisations up to Day 28 in a treatment arm with an increased rate of viral clearance compared with the negative control i.e. patients not receiving study drug
Days 0-28
Relationship between viral clearance, randomisation arm and other measures (covariates) and development of post- acute COVID-19 (i.e. long COVID)
Time Frame: Days 0-120
Score on post-acute COVID-19 (i.e. long COVID) questionnaire at day 120 - modified COVID-19 Yorkshire Rehabilitation Scale (C19 YRSm)
Days 0-120

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Oxford

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 30, 2021

Primary Completion (Estimated)

January 1, 2027

Study Completion (Estimated)

January 1, 2027

Study Registration Dates

First Submitted

September 7, 2021

First Submitted That Met QC Criteria

September 10, 2021

First Posted (Actual)

September 13, 2021

Study Record Updates

Last Update Posted (Actual)

February 19, 2026

Last Update Submitted That Met QC Criteria

February 16, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VIR21001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

With patient's consent, clinical data and results from blood analyses stored in the database may be shared according to the terms defined in the MORU data sharing policy with other researchers to use in the future.

Data generated from this study will adhere to the 2016 "Statement on data sharing in public health emergencies"(https://wellcome.ac.uk/press-release/statement-data-sharing-public-health-emergencies).

IPD Sharing Time Frame

after the main paper has been published

IPD Sharing Access Criteria

MORU Data Sharing Policy https://www.tropmedres.ac/units/moru-bangkok/bioethics-engagement/data-sharing.

The criteria for authorship will be consistent with the international guidelines (http://www.icmje.org/#author).

IPD Sharing Supporting Information Type

  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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