Ensitrelvir for Viral Persistence and Inflammation in People Experiencing Long COVID

Change in Patient-Reported Outcomes Measurement Information System (PROMIS)-29 Physical Health Summary Score from Baseline.

This measure will evaluate whether there is a difference between treatment with Ensitrelvir versus placebo on the PROMIS-29 scale between baseline and 30 days following administration. PROMIS-29 is a validated scale assessing physical function, anxiety, depression, fatigue, sleep disturbance, ability to participate in social activities, and pain. Each domain is scored on a 5-point scale (without any difficulty, with a little difficulty, with some difficulty, with much difficulty, unable to do). We will evaluate the change in the Physical Health Summary Score at these timepoints.

Time frame: Baseline and Day 30

Change in Patient-Reported Outcomes Measurement Information System (PROMIS)-29 Mental Health Summary Score from Baseline.

This measure will evaluate whether there is a difference between treatment with Ensitrelvir versus placebo on the PROMIS-29 scale between baseline 10 days following administration. PROMIS-29 is a validated scale assessing physical function, anxiety, depression, fatigue, sleep disturbance, ability to participate in social activities, and pain. Each domain is scored on a 5-point scale (without any difficulty, with a little difficulty, with some difficulty, with much difficulty, unable to do). We will evaluate the change in the Mental Health Summary Score at these timepoints.

Time frame: Baseline and Day 10

Change in Patient-Reported Outcomes Measurement Information System (PROMIS)-29 Mental Health Summary Score from Baseline.

This measure will evaluate whether there is a difference between treatment with Ensitrelvir versus placebo on the PROMIS-29 scale between baseline and day 30 following administration. PROMIS-29 is a validated scale assessing physical function, anxiety, depression, fatigue, sleep disturbance, ability to participate in social activities, and pain. Each domain is scored on a 5-point scale (without any difficulty, with a little difficulty, with some difficulty, with much difficulty, unable to do). We will evaluate the change in the Mental Health Summary Score at this timepoint.

Time frame: Baseline and Day 30

Change in Quality of Life (Global Health Score) on a 100-point Visual-Analogue Scale from Baseline

This measure will evaluate whether there is a difference between treatment with Ensitrelvir versus placebo on self-reported score on a 100-point visual-analogue scale, where 0 represents the worst health a person can imagine and 100 represents the best health a person can imagine.

Time frame: Baseline and Day 10

Change in Quality of Life Score (5-Item EuroQol EQ-5D-5L) Index Value Score from Baseline.

5-Item EuroQol EQ-5D-5L questions assess pain/difficulty in day-to-day activities over the past week.

Time frame: Baseline and Day 10

Change in Duke Activity Status Index (DASI) from Baseline

The Duke Activity Status Index is a patient-reported estimate of functional capacity, maximal oxygen consumption (VO2 max) and maximum metabolic equivalent of tasks (METs). The DASI questionnaire produces a score between 0 and 58.2 points, which is linearly correlated with a patient's VO2 max and METs, as measured from cardiopulmonary exercise testing (CPET). It inquires about a person's ability to perform self-care, walk, climb stairs, run, do house and yard work, engage in sexual intercourse, and perform moderate recreational activities.

Time frame: Baseline and Day 10

Change in Orthostatic Intolerance Score from Baseline

This measure will evaluate whether there is a difference between treatment with Ensitrelvir versus placebo on the OHQ scale between baseline and 10 days following administration. The scale assesses symptoms and their impact.

Time frame: Baseline and Day 10

Change in World Health Organization Disability Assessment Schedule 2.0 (WHO-DAS 2.0) questionnaire from Baseline

The World Health Organization Disability Assessment Schedule 2.0 questionnaire asks about difficulties due to health conditions. Health conditions include diseases or illnesses, other health problems that may be short or long lasting, injuries, mental or emotional problems, and problems with alcohol or drugs.

Time frame: Baseline and Day 10

Patient Global Impression of Change (PGIC) at D10

The self-report measure Patient Global Impression of Change (PGIC) reflects a patient's belief about the efficacy of treatment. We will use a modified PGIC scale which has been used to study pain syndromes and has been employed in other Long COVID clinical trials. It is a common data element developed by the National Institutes of Mental Health.

Time frame: Day 10

Change in Everyday Cognition Form instrument from Baseline

The ECog is an instrument that measures the decline in everyday cognitive and functional abilities that map to six cognitive domains, adapted specifically to describe change in abilities since having COVID. This version of the ECog questionnaire uses 41 questions to assess these domains.

Time frame: Baseline and Day 10

Change in 6 Minute Walking Test (6MWT) from Baseline

This measure will evaluate whether there is a difference between treatment with Ensitrelvir versus placebo on 6MWT performance between baseline and at 10 days following administration. The 6MWT requires an individual to walk at their normal pace for 6 minutes on a marked track (for example, a hallway). Vital signs are assessed, and the total distance covered is the primary outcome of interest.

Time frame: Baseline and Day 10

Change in Active Stand Test from Baseline

Measurements of heart rate and blood pressure measured after resting lying down, and at standardized increments for up to 10 minutes (as tolerated).

Time frame: Baseline and Day 10

Change in Neurocognition Index (NCI) score from the CNS-VS from Baseline

A neurocognitive assessment to assess motor, emotional, sensory, and cognitive function. It is available in English and Spanish and is administered using an iPad or computer.

Time frame: Baseline and Day 10