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History of Changes for Study: NCT04456153
Atovaquone for Treatment of COVID-19
Latest version (submitted December 12, 2021) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 June 30, 2020 None (earliest Version on record)
2 July 9, 2020 Study Status and Contacts/Locations
3 July 16, 2020 Sponsor/Collaborators, Contacts/Locations and Study Status
4 July 28, 2020 Recruitment Status, Study Status, Contacts/Locations and Oversight
5 January 14, 2021 Study Status
6 February 16, 2021 Recruitment Status, Study Status, Outcome Measures, Contacts/Locations and Study Design
7 November 10, 2021
Quality Control Review has not concluded Returned: November 19, 2021
Outcome Measures, Study Status, Document Section and Sponsor/Collaborators
8 November 26, 2021
Quality Control Review has not concluded Returned: November 29, 2021
Outcome Measures, Baseline Characteristics, Document Section, Adverse Events, IPDSharing, Study Design and Study Status
9 November 30, 2021
Quality Control Review has not concluded Returned: December 1, 2021
Outcome Measures and Study Status
10 December 12, 2021 Study Status, Outcome Measures
Comparison Format:

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Study NCT04456153
Submitted Date:  June 30, 2020 (v1)

Open or close this module Study Identification
Unique Protocol ID: STU-2020-0707
Brief Title: Atovaquone for Treatment of COVID-19
Official Title: Atovaquone for Treatment of COVID-19
Secondary IDs:
Open or close this module Study Status
Record Verification: June 2020
Overall Status: Not yet recruiting
Study Start: July 2020
Primary Completion: December 2020 [Anticipated]
Study Completion: March 2021 [Anticipated]
First Submitted: June 30, 2020
First Submitted that
Met QC Criteria:
June 30, 2020
First Posted: July 2, 2020 [Actual]
Last Update Submitted that
Met QC Criteria:
June 30, 2020
Last Update Posted: July 2, 2020 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: University of Texas Southwestern Medical Center
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring:
Open or close this module Study Description
Brief Summary:

The purpose of the current study is to accelerate the use of a clinically available therapeutic already FDA-approved for other indications in the setting of pandemic COVID-19 addressing a serious and emergent unmet medical need.

This is a randomized, double-blind study of atovaquone therapy in adult participants hospitalized with COVID-19. Approximately 60 participants who meet all eligibility criteria may be randomized in a 2:1 atovaquone/placebo ratio into one of the following treatment groups:

Treatment Group 1: continued standard of care therapy together with an oral dose of 1500 mg atovaquone twice daily (administered with a meal or snack) for up to 10 days

Treatment Group 2: continued standard of care therapy together with matching placebo

Detailed Description:

Design of the ATaQ COVID-19 Trial:

The purpose of the current study is to accelerate the use of a clinically available therapeutic already FDA-approved for other indications in the setting of pandemic COVID-19 addressing a serious and emergent unmet medical need. In consideration of the information included in this protocol, the overall risks to participants are outweighed by the potential benefits of atovaquone experimental therapy for the treatment of COVID-19. The benefit-risk balance for this study is considered positive.

Inclusion Criteria:

  1. Diagnosis of COVID-19 by positive RT-PCR requiring hospitalization within 72 hours
  2. Age ≥18 years old
  3. Able to provide informed consent, or (as allowed by IRB), immediate availability of designated legally authorized representative to provide consent by proxy
  4. Anticipated hospitalization for >48 hours

Exclusion Criteria

Patients who meet any of the following exclusion criteria are not to be enrolled in this study:

  1. Participation in any other clinical trial with antiviral activity against COVID-19
  2. Breastfeeding women
  3. Known hypersensitivity to atovaquone or formulation excipient
  4. Active treatment with rifampin
  5. HIV patients with AIDS requiring treatment for Pneumocystis jirovecii or Toxoplasma gondii
  6. Not expected to survive for 72 hours.
  7. >14 days from symptom onset

    Randomization:

    Patients who meet eligibility criteria and volunteer to participate will be randomized in a 2:1 ratio to atovaquone or placebo on Day 1 using computerized randomization. An unblinded investigational pharmacist not otherwise involved in the trial will know treatment assignment and dispense investigational product. As GI absorption of atovaquone increased when taken with food, so we will administer with a meal or snack.

    Blinding:

    Double blinding of treatment assignments will be performed in this study, with the study team and patients blinded to treatment assignment.

    The list of concomitant medications will be assessed only from Day 1 prior to enrollment to Day 15 or discharge, whichever is earlier.

    Patient Enrollment and Treatment Assignment:

    Entry into screening does not guarantee enrollment into the study. In order to manage the total study enrollment, the study researchers may suspend screening and/or enrollment at any at any time.

    Pretreatment Assessments:

    Screening Visit

    Patients will be screened within 2 days before randomization and dosing to determine eligibility for participation in the study. Screening will occur under approved HIPAA waiver for research to identify and screen all hospitalized COVID-19 positive patients on a daily basis.

    Obtain informed consent.

    After informed consent has been negotiated and the form signed, the following assessments will be performed to determine eligibility requirements as specified in the inclusion and exclusion criteria:

    • Review of focused medical history including the following information (e.g., date of first symptoms, overall symptoms, exposure source, demographics, baseline characteristics), allergies and past medical history.
    • Review and record medications and therapies for the current illness
    • Recording of vital signs (heart rate, temperature, blood pressure), body weight, and height
    • Documentation of respiratory support: Respiratory Rate, Oxygen supplementation: room air, nasal canula, face mask, non-rebreather, high-flow device, mechanical ventilation; and FiO2
    • SpO2 at rest or PaO2
    • Radiographic findings

    Study patients who qualify and volunteer to participate should be immediately consented and randomized. Randomization and initiation of dosing should occur on the same day if possible.

    Baseline/Day 1 Assessments

    The following evaluations are to be completed at the Day 1 visit. The investigator must have confirmed eligibility and signing of consent before proceeding with randomization on the Day 1 visit, followed immediately by first dose of investigational product. The assessments can be completed by the patient care team and do not need to be repeated by research personnel. The following assessments must be documented before administering investigational product, using the most recent data available at the time of randomization:

    Recording of vital signs (heart rate, temperature, blood pressure, body weight, height)

    Documentation of respiratory status:

    Respiratory rate

    Oxygen supplementation and FiO2: room air, nasal canula, face mask, non-rebreather, noninvasive ventilation or high flow oxygen devices, mechanical ventilation, or ECMO

    Oxygenation: (SpO2 or PaO2)

    Radiographic findings (if available)

    Review AEs and document concomitant medications

    Document Ordinal Scale at baseline

    Obtain saliva sample and nasopharyngeal swab sample for viral load quantification at day 1 prior to initial dose

    Obtain blood for research sample

    Daily Study Assessments (Days 2-15):

    The following evaluations are to be documented daily from Days 2 - 15 or until discharge whichever comes earlier, using the data recorded at or closest to 12:00 noon each day:

    • Vital signs (heart rate, temperature, blood pressure), body weight (if available).
    • Documentation of respiratory status: Respiratory rate, Oxygen supplementation and FiO2: room air, nasal canula, face mask, non-rebreather, noninvasive ventilation or high flow oxygen devices, mechanical ventilation, or ECMO
    • Oxygenation: (SpO2 or PaO2)
    • Radiographic findings (if available)
    • Review of AEs and document concomitant medications
    • Saliva sample for COVID-19 RT-PCR every 12 hours (Days 2-8)
    • Saliva sample for COVID-19 RT-PCR once daily (Days 9-15)
    • Additional blood draws for biobanking (Day 3, and 5 only)

    Clinical Laboratory Assessments:

    Clinical laboratory assessments will be conducted as clinically indicated and all laboratory testing will be completed by local laboratories. Clinical laboratory data to be captured in the trial database will include serum chemistries, liver function tests, complete blood counts including absolute neutrophil count, hs-CRP, D-dimer, ferritin, IL-6, troponin, NTpBNP.

    SARS-CoV-2 testing will include RT-qPCR to detect or quantify SARS-CoV-2 or virus sequencing results from saliva (baseline and daily until discharge or death, and 8 days and last day of hospitalization or Day 15 if still hospitalized.

    Pretreatment and posttreatment samples with detectable SARS-CoV-2 may be sequenced for resistance monitoring of the viral polymerase gene. For all clinical laboratory tests, except those at Day 1, when more than 1 result is available in a calendar day, the value closest to 12:00 noon should be captured in the eCRF. For Day 1 tests, the most recent result before dosing should be used.

    Physical Examination:

    No physical examination is mandated by the study protocol beyond the capture of vital signs (heart rate, respiratory rate, temperature, blood pressure, SpO2 at rest or PaO2) as documented clinically.

    Post-treatment Assessments:

    Treatment will continue to complete a 10 Day course or until viral clearance is documented, whichever occurs first.

    Telephone call on Day 15 and 29 for those discharged. The phone call will include a brief survey on symptoms and information on any re-hospitalizations.

    Final review of AEs and concomitant medication.

    Vital signs will be captured if still inpatient and the ordinal scale will be assessed.

Open or close this module Conditions
Conditions: COVID-19
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: Double (Participant, Investigator)
Allocation: Randomized
Enrollment: 60 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: standard of care therapy with atovaquone
The first treatment group will receive continued standard of care therapy together with an oral dose of 1500 mg atovaquone twice daily (administered with a meal or snack) for up to 10 days.
Drug: Experimental Group
Continued standard of care therapy together with an oral dose of 1500 mg atovaquone twice daily (administered with a meal or snack) for up to 10 days
Other Names:
  • Atovaquone
Placebo Comparator: standard of care therapy with matching placebo
The second treatment group will receive continued standard of care therapy together with matching placebo.
Drug: Placebo Group
Continued standard of care therapy together with matching placebo
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Viral Load
[ Time Frame: Up to 16 days ]

Log copy number/ml by RT-PCR) from saliva collection at Day 8 from trial entry, or at hospital discharge
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  1. Diagnosis of COVID-19 by positive RT-PCR requiring hospitalization within 72 hours
  2. Age ≥18 years old
  3. Able to provide informed consent, or (as allowed by IRB), immediate availability of designated legally authorized representative to provide consent by proxy
  4. Anticipated hospitalization for >48 hours

Exclusion Criteria:

  1. Participation in any other clinical trial with antiviral activity against COVID-19
  2. Breastfeeding women
  3. Known hypersensitivity to atovaquone or formulation excipient
  4. Active treatment with rifampin
  5. HIV patients with AIDS requiring treatment for Pneumocystis jirovecii or Toxoplasma gondii
  6. Not expected to survive for 72 hours. 7) >14 days from symptom onset
Open or close this module Contacts/Locations
Central Contact Person: Mamta Jain
Telephone: 214-648-7174
Email: Mamta.Jain@UTSouthwestern.edu
Central Contact Backup: Tianna Petersen
Telephone: 214-590-0611
Email: Tianna.Petersen@UTSouthwestern.edu
Study Officials: Mamta Jain, M.D.
Principal Investigator
University of Texas Southwestern Medical Center
Locations:
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Citations:
Links:
Available IPD/Information:

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