Trial Outcomes & Findings for Atovaquone for Treatment of COVID-19 (NCT NCT04456153)

NCT ID: NCT04456153

Last Updated: 2021-12-14

Results Overview

Between group differences in viral load (Log copy number/ml) using generalized linear mixed-effect models of repeated measures (GLMM), using data from all available samples

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 60 participants
• Primary outcome timeframe: Day 1 to Day 10
• Results posted on: 2021-12-14

Participant Flow

Participant milestones

Measure	Standard of Care Therapy With Matching Placebo The second treatment group will receive continued standard of care therapy together with matching placebo. Placebo Group: Continued standard of care therapy together with matching placebo	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. 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
Overall Study STARTED	19	41
Overall Study COMPLETED	19	41
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Atovaquone for Treatment of COVID-19

Baseline characteristics by cohort

Measure	Standard of Care Therapy With Atovaquone n=41 Participants 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.	Standard of Care Therapy With Matching Placebo n=19 Participants The second treatment group will receive continued standard of care therapy together with matching placebo.	Total n=60 Participants Total of all reporting groups
Age, Continuous	51.64 years n=5 Participants	49.4 years n=7 Participants	50.9 years n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants	7 Participants n=7 Participants	22 Participants n=5 Participants
Sex: Female, Male Male	26 Participants n=5 Participants	12 Participants n=7 Participants	38 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	29 Participants n=5 Participants	13 Participants n=7 Participants	42 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=5 Participants	6 Participants n=7 Participants	18 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized non-Hispanic White	31 Participants n=5 Participants	15 Participants n=7 Participants	46 Participants n=5 Participants
Race/Ethnicity, Customized Black	6 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants
Race/Ethnicity, Customized other	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment United States	41 participants n=5 Participants	19 participants n=7 Participants	60 participants n=5 Participants
log 10 viral load (copies/mL) atovaquone	5.25 log 10 RNA copies/mL STANDARD_DEVIATION 0.278 • n=5 Participants	0 log 10 RNA copies/mL STANDARD_DEVIATION 0 • n=7 Participants	5.25 log 10 RNA copies/mL STANDARD_DEVIATION 0.278 • n=5 Participants
log 10 viral load (copies/mL) Placebo	0 log 10 RNA copies/mL STANDARD_DEVIATION 0 • n=5 Participants	4.79 log 10 RNA copies/mL STANDARD_DEVIATION 0.408 • n=7 Participants	4.79 log 10 RNA copies/mL STANDARD_DEVIATION 0.408 • n=5 Participants

PRIMARY outcome

Timeframe: Day 1 to Day 10

Population: Change in viral load from day 1 to day 10 between intervention arm and placebo

Between group differences in viral load (Log copy number/ml) using generalized linear mixed-effect models of repeated measures (GLMM), using data from all available samples

Outcome measures

Measure	Overall Group n=60 Participants Comparison of experimental group to placebo	Atovaquone Group With Standard of Care Treatment n=41 Participants This arm received atovaquone 2: 1 in addition to the standard of care.	Placebo Plus Standard of Care n=19 Participants This arm received matched placebo in addition to the standard of care.
Primary Analysis	-1.906 log 10 (copies/mL) Interval -3.09 to 0.123	2.629 log 10 (copies/mL) Interval 1.652 to 3.606	4.073 log 10 (copies/mL) Interval 3.131 to 5.015

SECONDARY outcome

Timeframe: baseline to day7

Change in viral load at Day 3, 5, and 7 days. This shows the group differences between intervention and placebo and log 10 viral load at specific days 3, 5, and 7 for atovaquone arm and placebo arm.

Outcome measures

Measure	Overall Group n=60 Participants Comparison of experimental group to placebo	Atovaquone Group With Standard of Care Treatment n=41 Participants This arm received atovaquone 2: 1 in addition to the standard of care.	Placebo Plus Standard of Care n=19 Participants This arm received matched placebo in addition to the standard of care.
Secondary Between Group Differences in Viral Load day 1 to 3	0.129 log 10 (copies/mL) Interval -0.571 to 0.829	5.342 log 10 (copies/mL) Interval 4.548 to 6.135	4.406 log 10 (copies/mL) Interval 3.609 to 5.203
Secondary Between Group Differences in Viral Load day 1 to 5	0.107 log 10 (copies/mL) Interval -0.61 to 0.823	4.329 log 10 (copies/mL) Interval 3.785 to 4.874	3.760 log 10 (copies/mL) Interval 2.948 to 4.572
Secondary Between Group Differences in Viral Load day 1 to 7	-0.766 log 10 (copies/mL) Interval -1.534 to 0.002	3.804 log 10 (copies/mL) Interval 3.23 to 4.378	4.108 log 10 (copies/mL) Interval 3.27 to 4.946

SECONDARY outcome

Timeframe: baseline to day 10

Population: Between group differences Day 1 to day 10

Between group differences in viral load (Log copy number/ml) using GLMM stratified by

Outcome measures

Measure	Overall Group n=38 Participants Comparison of experimental group to placebo	Atovaquone Group With Standard of Care Treatment n=22 Participants This arm received atovaquone 2: 1 in addition to the standard of care.	Placebo Plus Standard of Care This arm received matched placebo in addition to the standard of care.
Change in Viral Load at Day 10 Stratified by Sex	-1.8732 log 10 viral load (copies/mL) Interval -3.8342 to 0.08779	0.555 log 10 viral load (copies/mL) Interval -1.9539 to 3.0639	—

SECONDARY outcome

Timeframe: baseline to day 3

Between group comparison of time to drop in viral load (Log copy number/ml) of 2 log units using Kaplan-Meier estimation. Examined the percentage of participants who achieved this viral load drop in 3 days.

Outcome measures

Measure	Overall Group n=41 Participants Comparison of experimental group to placebo	Atovaquone Group With Standard of Care Treatment n=19 Participants This arm received atovaquone 2: 1 in addition to the standard of care.	Placebo Plus Standard of Care This arm received matched placebo in addition to the standard of care.
Percentage With 2 Log Viral Load Drop at Day 3	15 percentage of participants	20 percentage of participants	—

SECONDARY outcome

Timeframe: Day 15

Ordinal scale 1 indicated death, and higher scores were various degrees of hospitalizations and incapacity to being out of hospital. Ordinal Scale 1-7 with higher score indicating improvement in clinical status. Change of ≥2 points on the ordinal scale by Day 15 using chi-square analysis

Outcome measures

Measure	Overall Group n=40 Participants Comparison of experimental group to placebo	Atovaquone Group With Standard of Care Treatment n=17 Participants This arm received atovaquone 2: 1 in addition to the standard of care.	Placebo Plus Standard of Care This arm received matched placebo in addition to the standard of care.
Number of Participants With Change in Ordinal Scale ≥2 Points by Day 15.	25 Participants	9 Participants	—

SECONDARY outcome

Timeframe: day 7

This is a alternative method of measurement of area which examines the viral load ( copies/ml )(y-axis) by day (x-axis) using the trapezoidal method. The area under the curve was calculated via the trapezoidal rule. As such, this is a numeric value that is different than the traditional use of the term "mean" or "median." However, in order to calculate a measure of error associated with this quantity, bootstrapping with 500 replications would need to be performed to assess statistical significance or lack thereof. The mean of the bootstrap samples could be reported as the "mean area under the curve."

Outcome measures

Measure	Overall Group n=41 Participants Comparison of experimental group to placebo	Atovaquone Group With Standard of Care Treatment n=19 Participants This arm received atovaquone 2: 1 in addition to the standard of care.	Placebo Plus Standard of Care This arm received matched placebo in addition to the standard of care.
Area Under the Curve Copies/ml*Day at Day 7	38.39 copies/mL*day	36.09 copies/mL*day	—

SECONDARY outcome

Timeframe: day 10

change in log RNA 10 day 1 to 10 stratified by remdesivir by GLMM

Outcome measures

Measure	Overall Group n=36 Participants Comparison of experimental group to placebo	Atovaquone Group With Standard of Care Treatment n=24 Participants This arm received atovaquone 2: 1 in addition to the standard of care.	Placebo Plus Standard of Care This arm received matched placebo in addition to the standard of care.
Stratifed by Remdesivir	-0.754 log 10 RNA copies/mL Interval -2.44 to 0.933	-2.010 log 10 RNA copies/mL Interval -4.513 to 0.494	—

Adverse Events

Atovaquone

Serious events: 7 serious events

Other events: 2 other events

Deaths: 6 deaths

Placebo

Serious events: 3 serious events

Other events: 0 other events

Deaths: 2 deaths

Serious adverse events

Measure	Atovaquone n=41 participants at risk Atovaquone plus standard of care. Grade 3 and 4 adverse events were collected.	Placebo n=19 participants at risk Matching placebo plus standard of care
Respiratory, thoracic and mediastinal disorders hypoxic respiratory failure	17.1% 7/41 • Number of events 7 • During hospitalization for an average of 10 days Collected grade 3 or 4 adverse events	15.8% 3/19 • Number of events 3 • During hospitalization for an average of 10 days Collected grade 3 or 4 adverse events

Other adverse events

Measure	Atovaquone n=41 participants at risk Atovaquone plus standard of care. Grade 3 and 4 adverse events were collected.	Placebo n=19 participants at risk Matching placebo plus standard of care
Gastrointestinal disorders Transaminitis	4.9% 2/41 • Number of events 2 • During hospitalization for an average of 10 days Collected grade 3 or 4 adverse events	0.00% 0/19 • During hospitalization for an average of 10 days Collected grade 3 or 4 adverse events

Additional Information

Dr. Mamta K. Jain

UT Southwestern Medical Center

Phone: 2140648-9914

Email: mamta.jain@utsouthwestern.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place