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NCT05041907 | RECRUITING | COVID-19

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

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 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.

Condition or disease

COVID-19

Intervention/treatment

Nirmatrelvir/ritonavir (e.g. PAXLOVID™)

Nitazoxanide

Molnupiravir and nirmatrelvir/ritonavir (e.g. PAXLOVID™)

Hydroxychloroquine

No treatment

Monoclonal antibodies

Fluoxetine

Molnupiravir

Sotrovimab

Ensitrelvir

Monoclonal antibodies

Favipiravir

Ivermectin

Remdesivir

Atilotrelvir/ritonavir

Metformin

Nirmatrelvir/ritonavir

Nirmatrelvir/ritonavir

Nirmatrelvir

Phase

PHASE2

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
Estimated Enrollment : 3800 participants
Masking : NONE
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 : 2021-09-30
Estimated Primary Completion Date : 2027-01
Estimated Study Completion Date : 2027-01

Information not available for Arms and Intervention/treatment

Ages Eligible for Study: 18 Years to 60 Years
Sexes Eligible for Study: ALL
Accepts Healthy Volunteers:
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 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
Finding Treatments for COVID-19: A Trial of Antiviral Pharmacodynamics in Early Symptomatic COVID-19 (PLATCOV)

Location Details

NCT05041907

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How to Participate

Want to participate in this study, select a site at your convenience, send yourself email to get contact details and prescreening steps.

Locations

RECRUITING

Brazil,

Federal University of Minas Gerais

Minas Gerais, Brazil,

RECRUITING

Laos,

Laos-Oxford-Mahosot Wellcome Trust Research Unit

Vientiane, Laos, 01000

RECRUITING

Nepal,

Sukraraj Tropical & Infectious Disease Hospital

kathmandu, Nepal,

TERMINATED

Pakistan,

The Aga Khan University Hospital

Karachi, Pakistan,

TERMINATED

Thailand,

Vajira hospital

Bangkok, Thailand, 10300

RECRUITING

Thailand,

Faculty of Tropical Medicine, Mahidol University

Bangkok, Thailand, 10400

TERMINATED

Thailand,

Bangplee Hospital

Mueang Samut Prakan, Thailand, 10540