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

Sponsor

University of Oxford (Other)

Overall Status

Recruiting

CT.gov ID

NCT05041907

Collaborator

(none)

750

Enrollment

Locations

Arms

Anticipated Duration (Months)

187.5

Patients Per Site

8.5

Patients Per Site Per Month

Study Details

Study Description

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:

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.

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.

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").

Study Design

Study Type:

Interventional

Anticipated 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 :

Sep 30, 2021

Anticipated Primary Completion Date :

Aug 1, 2023

Anticipated Study Completion Date :

Aug 1, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Rate of viral clearance for repurposed drugs [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
Rate of viral clearance of positive control (monoclonal antibodies) over time relative to the negative control [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
Rate of viral clearance for small novel molecule drugs [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

Viral kinetic levels in early COVID-19 disease [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
Number of antiviral treatment arms that show a positive signal (>90% probability of >5% acceleration in viral clearance) [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
Rates of viral clearance by treatment arm, as compared against REGN-COV2 (monoclonal antibody cocktail) [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

Rates of hospitalisation by treatment arm [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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Universidade Federal de Minas Gerais	Minas Gerais	Brazil
2	Vajira hospital	Bangkok	Thailand	10300
3	Faculty of Tropical Medicine, Mahidol University	Bangkok	Thailand	10400
4	Bangplee Hospital	Samut Prakan	Thailand	10540