The Prevent Severe COVID-19 (PRESECO) Study

• Sponsor: Appili Therapeutics Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04600895
• Collaborator: (none)
• Enrollment: 1,231
• Locations: 38
• Arms: 2
• Actual Duration (Months): 10.6
• Patients Per Site: 32.4
• Patients Per Site Per Month: 3

Study Details

Study Description

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.

Study Design

• Study Type: Interventional
• 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: Nov 30, 2020
• Actual Primary Completion Date: Oct 20, 2021
• Actual Study Completion Date: Oct 20, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Time to sustained clinical recovery [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) [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) [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 [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. [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 [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 [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 [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. [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 [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). [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). [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 [Up to day 28]

   Oral temperature (°C)

4. Safety Events: Vital Signs [Up to day 28]

   heart rate (BPM)

5. Safety Events: Vital Signs [Up to day 28]

   oxygen saturation (% O2)

6. Safety Events: Clinical laboratory testing [Day 1 and 10]

   CBC with differential

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

   BUN

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

   Electrolytes

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

   Creatinine

10. Safety Events: Clinical laboratory testing [Day 1 and 10]

    Random Blood Serum Glucose

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

    AST

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

    ALT

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

    Bilirubin

14. Safety Events: Clinical laboratory testing [Day 1 and 10]

    uric acid

15. Safety Events: Clinical laboratory testing [Day 1 and 10]

    SARS-CoV2 IgG

16. Safety Events: Clinical laboratory testing [Day 1 and 10]

    IL-6

17. Safety Events: Clinical laboratory testing [Day 1 and 10]

    IL-10

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

    ESR

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

    CRP

20. Safety Events: Clinical laboratory testing [Day 1 and 10]

    D-Dimer

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

    ferritin

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cahaba Research, Inc.	Pelham	Alabama	United States	35124
2	Absolute Clinical Research	Phoenix	Arizona	United States	85051
3	B.G Clinical Research Center, LLC	Little Rock	Arkansas	United States	72205
4	Xera Med Research	Boca Raton	Florida	United States	33487
5	Synergy Healthcare	Bradenton	Florida	United States	34208
6	Best Quality Research,Inc.	Hialeah	Florida	United States	33016
7	Elixia Clinical Research Collaborative	Hollywood	Florida	United States	33023
8	Homestead Associates In Research	Miami	Florida	United States	33032
9	Verus Clinical Research Corporation	Miami	Florida	United States	33125
10	Quality Professional HealthCare	Miami	Florida	United States	33126
11	Continental Clinical Research, LLC	Miami	Florida	United States	33144
12	Global Life Research Network, Llc	Miami	Florida	United States	33155
13	Sanitas Research, LLC	Miami	Florida	United States	33155
14	US Associates in Research, LLC	Miami	Florida	United States	33175
15	Biore'Search Institute Llc	Pembroke Pines	Florida	United States	33026
16	Luminous Clinical Research - South Florida Urgent Care	Pembroke Pines	Florida	United States	33029
17	Alliance Clinical Research of Tampa	Tampa	Florida	United States	33615
18	University of Massachusettts Medical School	Worcester	Massachusetts	United States	01655
19	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania	United States	19107
20	Frontier Clinical Research, LLC	Scottdale	Pennsylvania	United States	15683
21	Frontier Clinical Research, LLC	Smithfield	Pennsylvania	United States	15478
22	New Phase Research & Development	Knoxville	Tennessee	United States	37909
23	Next Level Urgent Care	Houston	Texas	United States	77057
24	Clinical Trial Network	Houston	Texas	United States	77074
25	Frontier Clinical Research	Kingwood	West Virginia	United States	26537
26	Centro de Pesquisas Clínicas de Natal	Natal	RN	Brazil
27	Hospital de Clinicas de Porto Alegre	Porto Alegre	RS	Brazil
28	LMK Servicos Medicos S/S	Porto Alegre	RS	Brazil
29	Nucleo de Pesquisa Clinica do Rio Grande do Sul	Porto Alegre	RS	Brazil
30	Pesquisare Saude S/S LTDA	Santo André	SP	Brazil
31	Centro Medico Mazzei	São Paulo		Brazil
32	Hospital Santa Paula	São Paulo		Brazil
33	Invesclinic Mx	Irapuato	Guanajuato	Mexico
34	Kohler & Milstein Research S.A. de C.V	Yucatán	Merida	Mexico
35	JM Research SC	Cuernavaca	Morelos	Mexico
36	Tecsi S.C.	Monterrey	Nuevo Leon	Mexico
37	Panamerican Clinical Research Mexico, S.A. de C. V.	Juriquilla	Queretaro	Mexico
38	Centro Medico Espiritu Santo	Tequisquiapan	Queretaro	Mexico

Sponsors and Collaborators

• Appili Therapeutics Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Appili Therapeutics Inc.
• ClinicalTrials.gov Identifier: NCT04600895
• Other Study ID Numbers: ATI0220
• First Posted: Oct 23, 2020
• Last Update Posted: Dec 3, 2021
• Last Verified: Nov 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: COVID-19; Favipiravir

Study Results

No Results Posted as of Dec 3, 2021