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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04600895
Recruitment Status : Completed
First Posted : October 23, 2020
Last Update Posted : December 3, 2021
Sponsor:
Information provided by (Responsible Party):
Appili Therapeutics Inc.

Brief Summary:
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

Condition or disease Intervention/treatment Phase
Covid19 Drug: Favipiravir Drug: Placebo Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1231 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Favipiravir for Patients With Mild to Moderate Disease From Novel Coronavirus (COVID-19)
Actual Study Start Date : November 30, 2020
Actual Primary Completion Date : October 20, 2021
Actual Study Completion Date : October 20, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Favipiravir
Favipiravir 200mg tablet
Drug: Favipiravir
Favipiravir

Placebo Comparator: Placebo
Placebo 200mg tablet
Drug: Placebo
Placebo




Primary Outcome Measures :
  1. Time to sustained clinical recovery [ Time Frame: From Day 0 to Day 28 ]
    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.


Secondary Outcome Measures :
  1. Proportion of subjects with COVID-19 progression (narrow progression) [ Time Frame: From study day 3 to day 28 ]
    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)

  2. Proportion of subjects with COVID-19 progression (broad progression) [ Time Frame: From study day 3 to day 28 ]
    • Proportion of subjects with COVID-19 progression, defined as the occurrence from study day 3 onward of any ED visit for COVID worsening or shortness of breath OR hospitalization for COVID worsening or shortness of breath OR death OR the development of symptomatic worsening from study day 3 onward (defined as >2 additional COVID symptoms at a level of moderate or severe which have not existed on study day 1 or fever (temperature of ≥38.0ºC) which has not existed on study day 1 or oxygen desaturation (O2 saturation <94%) which has not existed on study day 1) (broad progression)

  3. Viral Shedding Sub-Study [ Time Frame: From study day 3 to day 28 ]
    Time (number of days) to negative conversion (defined as <100 RNA copies) of detectable SARS-CoV-2 viral RNA (defined as >100 RNA copies) in negative RT-PCR assays of saliva, from start of study treatment to study day 10. Included: all subjects with a positive PCR on study day 1 or 2 or 3. The endpoint will be evaluated from study day 3 onward.

  4. Proportion of subjects showing sustained clinical recovery by study Day 3, 5, 7, 10, 14, 21. [ Time Frame: Day 3, 5, 7, 10, 14, 21. ]
    Proportion of subjects showing sustained clinical recovery by study Day 3, 5, 7, 10, 14, 21.

  5. Proportion of subjects showing resolution of Symptoms by Days 3, 5, 7, 10, 14, 21 [ Time Frame: Days 3, 5, 7, 10, 14, 21 ]
    Proportion of subjects showing resolution of Symptoms by Days 3, 5, 7, 10, 14, 21, where resolution is defined as symptom severity of 0 for all symptoms as well as temperature of <38.0 ºC as well as oxygen saturation of ≥94%.

  6. Proportion of patients showing negative conversion of detectable SARS-CoV-2 viral RNA in saliva [ Time Frame: Study Days 3, 5, 7, and 10. ]
    Defined as SARS-CoV-2 viral load conversion from >100 on study day 1 or 2 or 3 to <100 thereafter) on Study Days 3, 5, 7, and 10. Included: all subjects with a positive PCR on study day 1 or 2 or 3.

  7. Proportion of patients showing negative conversion of positive SARS-CoV-2 viral culture in saliva on Study Days 3, 5, 7 and 10 [ Time Frame: Study Days 3, 5, 7 and 10 ]
    Subjects with a positive saliva SARS-CoV-2 PCR on any study day will have viral cultures performed. Subjects with a positive viral culture on day 1 or 2 or 3 will be included in this analysis.

  8. Proportion of subjects dying from any cause over an assessment period from start of study treatment until Day 28. [ Time Frame: Until day 28 ]
    Proportion of subjects dying from any cause over an assessment period from start of study treatment until Day 28.

  9. Proportion of subject with COVID-19 progression [ Time Frame: Up to day 28 ]
    Proportion of subject with COVID-19 progression, where progression is defined as the occurrence at any point from study day 1 to study day 28 of emergency department (ED) visit for any reason OR hospitalization for any reason.


Other Outcome Measures:
  1. Adverse Events: Number (and proportion) of patients reporting treatment emergent adverse events (TEAEs) (by MedDRA system organ class and preferred term). [ Time Frame: Up to day 28 ]
    Number (and proportion) of patients reporting treatment emergent adverse events (TEAEs) (by MedDRA system organ class and preferred term).

  2. Adverse Events: Number (and proportion) of patients reporting serious treatment emergent adverse events (TEAEs) (by MedDRA system organ class and preferred term). [ Time Frame: Up to day 28 ]
    Number (and proportion) of patients reporting serious treatment emergent adverse events (TEAEs) (by MedDRA system organ class and preferred term).

  3. Safety Events: Vital Signs [ Time Frame: Up to day 28 ]
    Oral temperature (°C)

  4. Safety Events: Vital Signs [ Time Frame: Up to day 28 ]
    heart rate (BPM)

  5. Safety Events: Vital Signs [ Time Frame: Up to day 28 ]
    oxygen saturation (% O2)

  6. Safety Events: Clinical laboratory testing [ Time Frame: Day 1 and 10 ]
    CBC with differential

  7. Safety Events: Clinical laboratory testing [ Time Frame: Day 1 and 10 ]
    BUN

  8. Safety Events: Clinical laboratory testing [ Time Frame: Day 1 and 10 ]
    Electrolytes

  9. Safety Events: Clinical laboratory testing [ Time Frame: Day 1 and 10 ]
    Creatinine

  10. Safety Events: Clinical laboratory testing [ Time Frame: Day 1 and 10 ]
    Random Blood Serum Glucose

  11. Safety Events: Clinical laboratory testing [ Time Frame: Day 1 and 10 ]
    AST

  12. Safety Events: Clinical laboratory testing [ Time Frame: Day 1 and 10 ]
    ALT

  13. Safety Events: Clinical laboratory testing [ Time Frame: Day 1 and 10 ]
    Bilirubin

  14. Safety Events: Clinical laboratory testing [ Time Frame: Day 1 and 10 ]
    uric acid

  15. Safety Events: Clinical laboratory testing [ Time Frame: Day 1 and 10 ]
    SARS-CoV2 IgG

  16. Safety Events: Clinical laboratory testing [ Time Frame: Day 1 and 10 ]
    IL-6

  17. Safety Events: Clinical laboratory testing [ Time Frame: Day 1 and 10 ]
    IL-10

  18. Safety Events: Clinical laboratory testing [ Time Frame: Day 1 and 10 ]
    ESR

  19. Safety Events: Clinical laboratory testing [ Time Frame: Day 1 and 10 ]
    CRP

  20. Safety Events: Clinical laboratory testing [ Time Frame: Day 1 and 10 ]
    D-Dimer

  21. Safety Events: Clinical laboratory testing [ Time Frame: Day 1 and 10 ]
    ferritin



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 and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

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): NCT04600895


Locations
Show Show 38 study locations
Sponsors and Collaborators
Appili Therapeutics Inc.
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Responsible Party: Appili Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT04600895    
Other Study ID Numbers: ATI0220
First Posted: October 23, 2020    Key Record Dates
Last Update Posted: December 3, 2021
Last Verified: November 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
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
Favipiravir
Antiviral Agents
Anti-Infective Agents