The Prevent Severe COVID-19 (PRESECO) Study (PRESECO)

Favipiravir for Patients With Mild to Moderate Disease From Novel Coronavirus (COVID-19)

Double-blinded, placebo control, randomized, phase-3 clinical trial to evaluate clinical efficacy of Favipiravir in patients with mild to moderate symptoms related to COVID-19 infection

Study Overview

• Status: Completed
• Conditions: Covid19
• Intervention / Treatment: Drug: Placebo; Drug: Favipiravir

Detailed Description

COVID-19 starts as a pure viral infection and evolves into a multifactorial disease with components of hyper immune activation, end organ damage, and fibrosis. Suppression of viral replication is expected to be impactful early in the course of disease. The ability to mitigate the symptoms at an early stage will prevent progression to severe COVID-19 and can save many lives. Early treatment could also reduce viral shedding, diminishing the period of infectivity and decreasing the number of secondary cases.

• Study Type: Interventional
• Enrollment (Actual): 1187
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • São Paulo, Brazil
    • Hospital Santa Paula
  • São Paulo, Brazil
    • Centro Medico Mazzei
  • RN
    • Natal, RN, Brazil
      • Centro de Pesquisas Clínicas de Natal
  • RS
    • Porto Alegre, RS, Brazil
      • Hospital de Clinicas de Porto Alegre
    • Porto Alegre, RS, Brazil
      • LMK Serviços Médicos S/S
    • Porto Alegre, RS, Brazil
      • Núcleo de Pesquisa Clínica do Rio Grande do Sul
  • SP
    • Santo André, SP, Brazil
      • Pesquisare Saude S/S Ltda
• Mexico
  • Guanajuato
    • Irapuato, Guanajuato, Mexico
      • Invesclinic Mx
  • Merida
    • Yucatán, Merida, Mexico
      • Kohler & Milstein Research S.A. de C.V
  • Morelos
    • Cuernavaca, Morelos, Mexico
      • JM Research SC
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico
      • Tecsi S.C.
  • Queretaro
    • Juriquilla, Queretaro, Mexico
      • Panamerican Clinical Research Mexico, S.A. de C. V.
    • Tequisquiapan, Queretaro, Mexico
      • Centro Medico Espiritu Santo
• United States
  • Alabama
    • Pelham, Alabama, United States, 35124
      • Cahaba Research, Inc.
  • Arizona
    • Phoenix, Arizona, United States, 85051
      • Absolute Clinical Research
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • B.G Clinical Research Center, LLC
  • Florida
    • Boca Raton, Florida, United States, 33487
      • Xera Med Research
    • Bradenton, Florida, United States, 34208
      • Synergy Healthcare
    • Hialeah, Florida, United States, 33016
      • Best Quality Research,Inc.
    • Hollywood, Florida, United States, 33023
      • Elixia Clinical Research Collaborative
    • Miami, Florida, United States, 33032
      • Homestead Associates in Research
    • Miami, Florida, United States, 33155
      • Global Life Research Network, Llc
    • Miami, Florida, United States, 33175
      • US Associates in Research, LLC
    • Miami, Florida, United States, 33125
      • Verus Clinical Research Corporation
    • Miami, Florida, United States, 33126
      • Quality Professional HealthCare
    • Miami, Florida, United States, 33144
      • Continental Clinical Research, LLC
    • Miami, Florida, United States, 33155
      • Sanitas Research, LLC
    • Pembroke Pines, Florida, United States, 33029
      • Luminous Clinical Research - South Florida Urgent Care
    • Pembroke Pines, Florida, United States, 33026
      • Biore'Search Institute Llc
    • Tampa, Florida, United States, 33615
      • Alliance Clinical Research of Tampa
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusettts Medical School
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
    • Scottdale, Pennsylvania, United States, 15683
      • Frontier Clinical Research, LLC
    • Smithfield, Pennsylvania, United States, 15478
      • Frontier Clinical Research, LLC
  • Tennessee
    • Knoxville, Tennessee, United States, 37909
      • New Phase Research & Development
  • Texas
    • Houston, Texas, United States, 77074
      • Clinical Trial Network
    • Houston, Texas, United States, 77057
      • Next Level Urgent Care
  • West Virginia
    • Kingwood, West Virginia, United States, 26537
      • Frontier Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults age 18 or older
• Tested positive for SARS-CoV-2 by RT-PCR assay using a respiratory tract sample (either nasopharyngeal swab OR oropharyngeal swab OR nasal aspirate OR tracheobronchial aspirate OR saliva) collected within 72 hours of randomization
• Stated willingness to give their written informed consent to participate in the study
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Males must be sterile, OR agree not to donate semen AND agree to strictly adhere to contraceptive measures during the study and for 7 days following the last dose of study medication
• Females must be unable to bear children, OR ensure that their male partner is incapable of fathering a child, OR, if of childbearing potential will strictly adhere to contraceptive measures during the study and for seven days following the last dose of study medication
• Females must agree to stop breast-feeding prior to first dose of study drug and through seven days after completing therapy
• Females must have a negative pregnancy test at screening
• Ability to take oral medication and be willing to adhere to the favipiravir/placebo regimen
• Subject has access to a smart phone, tablet, or PC
• Minimal baseline severity score for COVID-19-related symptoms: at least two symptoms with a score of 2 or higher. COVID-19-related symptoms (excluding changes in the sense of taste or smell) include:
• stuffy or runny nose
• sore throat
• shortness of breath
• cough
• lack of energy or tiredness
• muscle or body aches
• headache
• chills or shivering
• feeling hot or feverish
• nausea
• diarrhea
• vomiting

Exclusion Criteria:

• O2 saturation <94%
• Shortness of breath at rest
• Heart rate ≥ 125 per minute
• COVID-19 symptoms first presented >5 days prior to randomization
• Requirement for hospitalization at the time of enrollment
• Participation in another trial or use of any experimental treatment for COVID-19
• Treatment with high steroid dose i.e. >30 mg/day prednisolone equivalent (excluding stable chronic treatment) or remdesivir or anyone receiving SARS-CoV-2 monoclonal antibodies within 3 months prior to enrollment
• Known sepsis or organ dysfunction/ failure
• Known infection with a respiratory virus other than SARS-CoV2 (e.g. Influenza) or any known bacterial infection (affecting the respiratory system or any other system)
• Inability to adhere to study requirements
• For premenopausal women: unwilling or unable to use effective birth control measures
• Known allergy to favipiravir
• Known end-stage kidney disease or requiring hemodialysis or continuous ambulatory peritoneal dialysis (CAPD)
• Known liver impairment greater than Child-Pugh A
• Psychiatric illness that is not well controlled (defined as stable on a regimen for more than one year).
• Known elevated uric acid levels in the past year or taking uric acid lowering medications (allopurinol, febuxostat)
• History of hereditary xanthinuria or history of xanthine urolithiasis.
• History of gout or actively being treated for gout.
• Current use of the following medications, which cannot be discontinued for the duration of the study: pyrazinamide, hydralazine, more than 3000 mg of acetaminophen per day.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Favipiravir; Favipiravir 200mg tablet	Drug: Favipiravir; Favipiravir
Placebo Comparator: Placebo; Placebo 200mg tablet	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Sustained Clinical Recovery	The endpoint will be considered to have been met at the earliest time point at which the subject has reached Sustained Alleviation of Symptoms (Symptoms related to smell or taste are not included in the primary endpoint) reported by the patient have reached a severity of "0 - none" or "1 - mild" in assessments for 4-point scale assessments and not known to have redeveloped any COVID-19 associated signs and symptoms (not including reduced sense of taste or smell) in a severity beyond mild for 4 consecutive days when assessed from the start of study treatment to day 28. To meet the primary endpoint, subjects must survive with no hospitalization to day 28.	From Day 0 to Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Subjects With COVID-19 Progression (Narrow Progression)	Proportion of subjects with COVID-19 progression, where progression is defined as the occurrence from study day 3 onward of any emergency department (ED) visit for COVID-19 worsening or shortness of breath OR hospitalization for COVID-19 worsening or shortness of breath OR death (narrow progression)	From study day 3 to day 28

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events: Number (and proportion) of patients reporting treatment emergent adverse events (TEAEs) (by MedDRA system organ class and preferred term).	Number (and proportion) of patients reporting treatment emergent adverse events (TEAEs) (by MedDRA system organ class and preferred term).	Up to day 28
Adverse Events: Number (and proportion) of patients reporting serious treatment emergent adverse events (TEAEs) (by MedDRA system organ class and preferred term).	Number (and proportion) of patients reporting serious treatment emergent adverse events (TEAEs) (by MedDRA system organ class and preferred term).	Up to day 28
Safety Events: Vital Signs	Oral temperature (°C)	Up to day 28
Safety Events: Vital Signs	heart rate (BPM)	Up to day 28
Safety Events: Vital Signs	oxygen saturation (% O2)	Up to day 28
Safety Events: Clinical laboratory testing	CBC with differential	Day 1 and 10
Safety Events: Clinical laboratory testing	BUN	Day 1 and 10
Safety Events: Clinical laboratory testing	Electrolytes	Day 1 and 10
Safety Events: Clinical laboratory testing	Creatinine	Day 1 and 10
Safety Events: Clinical laboratory testing	Random Blood Serum Glucose	Day 1 and 10
Safety Events: Clinical laboratory testing	AST	Day 1 and 10
Safety Events: Clinical laboratory testing	ALT	Day 1 and 10
Safety Events: Clinical laboratory testing	Bilirubin	Day 1 and 10
Safety Events: Clinical laboratory testing	uric acid	Day 1 and 10
Safety Events: Clinical laboratory testing	SARS-CoV2 IgG	Day 1 and 10
Safety Events: Clinical laboratory testing	IL-6	Day 1 and 10
Safety Events: Clinical laboratory testing	IL-10	Day 1 and 10
Safety Events: Clinical laboratory testing	ESR	Day 1 and 10
Safety Events: Clinical laboratory testing	CRP	Day 1 and 10
Safety Events: Clinical laboratory testing	D-Dimer	Day 1 and 10
Safety Events: Clinical laboratory testing	ferritin	Day 1 and 10

Collaborators and Investigators

• Sponsor: Appili Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2020
• Primary Completion (Actual): October 20, 2021
• Study Completion (Actual): October 20, 2021

Study Registration Dates

• First Submitted: September 15, 2020
• First Submitted That Met QC Criteria: October 22, 2020
• First Posted (Actual): October 23, 2020

Study Record Updates

• Last Update Posted (Actual): March 29, 2024
• Last Update Submitted That Met QC Criteria: March 27, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Anti-Infective Agents; Antiviral Agents; Favipiravir
• Other Study ID Numbers: ATI0220

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No