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

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ClinicalTrials.gov Identifier: NCT05041907
Recruitment Status : Recruiting
First Posted : September 13, 2021
Last Update Posted : January 12, 2022
Sponsor:
Information provided by (Responsible Party):
University of Oxford

Brief 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. In this randomised 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: potentially effective repurposed antiviral drugs;

B: Positive control: we will initially include the REGN-COV2 (monoclonal antibody cocktail); and later:

C: any future small molecule drugs that pass phase 1 testing.

PLATCOV study is funded by ACT-Accelerator Therapeutics Partnership through the Wellcome Trust. The grant reference number is 223195/Z/21/Z


Condition or disease Intervention/treatment Phase
COVID-19 Drug: Favipiravir Drug: Monoclonal antibodies Drug: Ivermectin Other: No treatment Drug: Remdesivir Phase 2

Detailed Description:

The platform trial will assess drugs with potential SARS-CoV-2 antiviral activity of three general types:

A. Repurposed potential antiviral drugs (initially from: hydroxychloroquine, ivermectin, lopinavir-ritonavir, miglustat, remdesivir, nitazoxanide, nebulised unfractionated heparin (UFH), favipiravir)

Repurposed drugs are already recommended in some countries. Showing that they do not have a significant antiviral activity is as important as showing that they do.

B. Positive control: monoclonal antibody initially

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. Monoclonal antibodies are expensive and cannot be produced at large scale currently, but this may change in the near future.

C. Novel small molecule drugs that have gone through phase 1 testing

Each site will include a negative control arm consisting of patients not receiving any study drug except for antipyretics- paracetamol.

At any given time in the study, it is possible that not all intervention arms are available. Randomisation ratios will be uniform across all available treatment arms of type A and B and the control arm in each site. Once interventions of type C (novel drugs) are added to the platform, response adaptive randomisation will apply ("pick the winner").

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 750 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Finding Treatments for COVID-19: A Phase 2 Multi-centre Adaptive Platform Trial to Assess Antiviral Pharmacodynamics in Early Symptomatic COVID-19 (PLATCOV)
Actual Study Start Date : September 30, 2021
Estimated Primary Completion Date : August 2023
Estimated Study Completion Date : August 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Positive control (monoclonals) Drug: Monoclonal antibodies
Monoclonal antibodies: 1,200mg casirivimab/ 1,200mg imdevimab given once on D0

Experimental: Favipiravir Drug: Favipiravir
Favipiravir 1800mg BD D0 and 800mg BD for a further 6/7.

Experimental: Ivermectin Drug: Ivermectin
Ivermectin 600micrograms/kg/day for 7/7.

Experimental: Remdesivir Drug: Remdesivir
Remdesivir 200mg D0 and 100mg for a further 4/7.

Negative control group Other: No treatment
No treatment (except antipyretics- paracetamol)




Primary Outcome Measures :
  1. Rate of viral clearance for repurposed drugs [ Time Frame: Days 0-7 ]
    Change in the gradient of the slope of the semi-logarithmic plot of quantitative viral load in serial oropharyngeal swabs versus time for patients in a treatment arm, compared with patients not receiving study drug, i.e. negative control

  2. Rate of viral clearance of positive control (monoclonal antibodies) over time relative to the negative control [ Time Frame: Days 0-7 ]
    Change in the gradient of the slope of the semi-logarithmic plot of quantitative viral load in serial oropharyngeal swabs versus time for patients in a treatment arm, compared with patients not receiving study drug, i.e. negative control

  3. Rate of viral clearance for small novel molecule drugs [ Time Frame: Days 0-7 ]
    Change in the gradient of the slope of the semi-logarithmic plot of quantitative viral load in serial oropharyngeal swabs versus time for patients in a treatment arm, compared with patients not receiving study drug, i.e. negative control


Secondary Outcome Measures :
  1. Viral kinetic levels in early COVID-19 disease [ Time Frame: Days 0-7 ]
    Change in the gradient of the slope of the semi-logarithmic plot of quantitative viral load in serial oropharyngeal swabs versus time for patients in a treatment arm, compared with patients not receiving study drug, i.e. negative control

  2. Number of antiviral treatment arms that show a positive signal (>90% probability of >5% acceleration in viral clearance) [ Time Frame: Days 0-7 ]
    Change in the gradient of the slope of the semi-logarithmic plot of quantitative viral load in serial oropharyngeal swabs versus time for patients in a treatment arm, compared with patients not receiving study drug, i.e. negative control

  3. Rates of viral clearance by treatment arm, as compared against REGN-COV2 (monoclonal antibody cocktail) [ Time Frame: Days 0-7 ]
    Change in the gradient of the slope of the semi-logarithmic plot of quantitative viral load in serial oropharyngeal swabs versus time for patients in a treatment arm, compared with patients not receiving study drug, i.e. negative control


Other Outcome Measures:
  1. Rates of hospitalisation by treatment arm [ 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 50 years at time of consent with early symptomatic COVID-19
  • SARS-CoV-2 positive by lateral flow antigen test
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05041907


Contacts
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Contact: William Schilling, MD +662 203 6333 william@tropmedres.ac
Contact: Nicholas J White, Prof. +662 203 6333 nickw@tropmedres.ac

Locations
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Thailand
Vajira hospital Recruiting
Bangkok, Thailand, 10300
Contact: Vasin Chotivanich, MD       vasinvasin@gmail.com   
Faculty of Tropical Medicine, Mahidol University Recruiting
Bangkok, Thailand, 10400
Contact: Weerapong Phumratanaprapin, MD       weerapong.phu@mahidol.ac.th   
Bangplee Hospital Recruiting
Samut Prakan, Thailand, 10540
Contact: Pongtorn Hanboonkunupakarn, MD       Pongtornmd18@gmail.com   
Sponsors and Collaborators
University of Oxford
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Responsible Party: University of Oxford
ClinicalTrials.gov Identifier: NCT05041907    
Other Study ID Numbers: VIR21001
First Posted: September 13, 2021    Key Record Dates
Last Update Posted: January 12, 2022
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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).

Supporting Materials: Clinical Study Report (CSR)
Analytic Code
Time Frame: after the main paper has been published
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).

URL: http://wellcome.ac.uk/press-release/statement-data-sharing-public-health-emergencies

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Oxford:
COVID-19
Phase 2
Antiviral Pharmacodynamics
Additional relevant MeSH terms:
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COVID-19
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Ivermectin
Remdesivir
Favipiravir
Antibodies
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Antiparasitic Agents
Anti-Infective Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents