Clinical trial NCT04346628: Oral Favipiravir Compared to Placebo in Subjects With Mild COVID-19
Official title: A Phase 2 Randomized, Double Blinded, Placebo Controlled Study of Oral Favipiravir Compared to Standard Supportive Care in Subjects With Mild or Asymptomatic COVID-19
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sars-CoV2
COVID-19
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2020-04-15
Enrollment: 149
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this study is to evaluate the efficacy of oral favipiravir plus standard of care treatment (SOC) compared with placebo plus SOC in reducing the duration of shedding of SARS-CoV2 virus in patients with mild or asymptomatic COVID-19.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of COVID-19 disease:

  * If symptomatic, presence of mild to moderate symptoms without signs of respiratory distress, with positive for SARS-CoV-2 diagnostic assay within 72 hours prior to.informed consent.
  * If asymptomatic, initial diagnosis obtained no more than 72 hours prior to informed consent
* Subject agrees to maintain home or other quarantine as recommended by the study physician, except to visit the study site as required by the protocol
* Members of the same household may participate in the study as long as the inclusion and exclusion criteria are met
* Males must be sterile, OR agree not to donate semen AND agree to strictly adhere to contraceptive measures during the study and for seven 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
* Participant agrees to maintain home or other quarantine as recommended by the study physician, except to visit the study site as required by the protocol

Exclusion Criteria:

* Concomitant bacterial respiratory infection documented by respiratory culture. NOTE: Subjects on empirical antibiotic treatment for possible but unproven bacterial pneumonia, but who are positive for SARS-CoV-2, are allowed in the study (will be randomized to the same treatment to maintain blinding).
* History of abnormal uric acid metabolism.
* History of hypersensitivity to an anti-viral nucleoside-analog drug targeting a viral RNA polymerase.
* Abnormal laboratory test results at screening:
* Use of adrenocorticosteroids (except topical or inhaled preparations or oral preparations equivalent to or less than 10 mg of oral prednisone) or immunosuppressive or immunomodulatory drugs (e.g., immunosuppressants, anticancer drugs, interleukins, interleukin antagonists or interleukin receptor blockers). NOTE: Treatment of study participants following institutional COVID-19 treatment policies or guidelines, including the use of immunomodulatory medications, is permitted. This excludes treatment with agents that have the potential for direct antiviral activity, including convalescent plasma and NO, and co-enrollment into other clinical studies that evaluate investigational agents for COVID-19.
* Serious chronic disease (e.g., human immunodeficiency virus \[HIV\], cancer requiring chemotherapy within the preceding 6 months, and/or moderate or severe hepatic insufficiency).
* Previously received favipiravir within the past 30 days.
* Advanced kidney disease
* Advanced liver disease
* History of alcohol or drug abuse in the previous two years.
* Psychiatric illness that is not well controlled (defined as stable on a regimen for more than one year).
* Taken another investigational drug within the past 30 days.
* Seemed by the Investigator to be ineligible for any reason.

Primary outcomes:
measure: Time Until Cessation of Oral Shedding of SARS-CoV-2 Virus
timeFrame: Up to 28 days
Secondary outcomes:
measure: Sars-CoV-2 Viral Load
timeFrame: Up to 28 days
measure: Count of Participants With Clinical Worsening of COVID-19 Disease
timeFrame: Up to 28 days
measure: Count of Participants With Development of SARS-CoV-2 Antibodies
timeFrame: Up to 28 days
measure: Time Until Cessation of Symptoms
timeFrame: Up to 28 days
measure: Count of Participant With Absence of Development of Any Symptoms
timeFrame: Up to 28 days
measure: Cmax of Favipiravir
timeFrame: Days 1 and 10 (samples taken 30 minutes prior to and 1 hour following favipiravir administration)
measure: Cmin of Favipiravir
timeFrame: Days 1 and 10 (samples taken 30 minutes prior to and 1 hour following favipiravir administration)
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University
state: California
Study officials:
affiliation: Stanford University
name: Yvonne (Bonnie) A Maldonado, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Holubar M, Subramanian A, Purington N, Hedlin H, Bunning B, Walter KS, Bonilla H, Boumis A, Chen M, Clinton K, Dewhurst L, Epstein C, Jagannathan P, Kaszynski RH, Panu L, Parsonnet J, Ponder EL, Quintero O, Sefton E, Singh U, Soberanis L, Truong H, Andrews JR, Desai M, Khosla C, Maldonado Y. Favipiravir for Treatment of Outpatients With Asymptomatic or Uncomplicated Coronavirus Disease 2019: A Double-Blind, Randomized, Placebo-Controlled, Phase 2 Trial. Clin Infect Dis. 2022 Nov 30;75(11):1883-1892. doi: 10.1093/cid/ciac312.
citation: Jacobson KB, Rao M, Bonilla H, Subramanian A, Hack I, Madrigal M, Singh U, Jagannathan P, Grant P. Patients With Uncomplicated Coronavirus Disease 2019 (COVID-19) Have Long-Term Persistent Symptoms and Functional Impairment Similar to Patients with Severe COVID-19: A Cautionary Tale During a Global Pandemic. Clin Infect Dis. 2021 Aug 2;73(3):e826-e829. doi: 10.1093/cid/ciab103.