Trial Outcomes & Findings for Study of LAU-7b for the Treatment of Long COVID in Adults (NCT NCT05999435)

Results Overview

The SF-36 questionnaire consists of 36 items grouped in eight health domains, vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health, that can be aggregated to two summary scales, physical component summary (PCS ) and mental component summary (MCS). The PCS summarizes the physical status and constitutes the primary outcome variable. Each health domain score consists of the sum scores of the assigned questions. Scores are weighted and transformed into a scale ranging from 0 (greatest possible health restrictions, ie, severe disability) to 100 (no health restrictions). A higher score means a better physical status. The calculation process for the PCS has been previously described by Taft et al. 2001.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

272 participants

Primary outcome timeframe

Week 0 and 12

Results posted on

2026-01-06

Participant Flow

The study was conducted at 5 specialized Long COVID medical clinics in Quebec. A total of 285 potential participants were screened from 15 November 2023 to 07 May 2024

Participant milestones

Participant milestones
Measure	LAU-7b for 3 Cycles (Arm 1, AAA) Three cycles of 14 days of once-a-day intake of LAU-7b, each followed by a treatment intake pause of 14 days.	LAU-7b for 1 Cycle, Then Placebo (Arm 2, APP) One cycle of 14 days of once-a-day intake of LAU-7b followed by two cycles of 14 days of placebo administered similarly, each followed by a treatment intake pause of 14 days.	Placebo for 3 Cycles (Arm 3, PPP) Three cycles of 14 days of once-a-day intake of placebo, each followed by a treatment intake pause of 14 days
Overall Study STARTED	91	91	90
Overall Study COMPLETED	88	90	90
Overall Study NOT COMPLETED	3	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	LAU-7b for 3 Cycles (Arm 1, AAA) Three cycles of 14 days of once-a-day intake of LAU-7b, each followed by a treatment intake pause of 14 days.	LAU-7b for 1 Cycle, Then Placebo (Arm 2, APP) One cycle of 14 days of once-a-day intake of LAU-7b followed by two cycles of 14 days of placebo administered similarly, each followed by a treatment intake pause of 14 days.	Placebo for 3 Cycles (Arm 3, PPP) Three cycles of 14 days of once-a-day intake of placebo, each followed by a treatment intake pause of 14 days
Overall Study Adverse Event	1	0	0
Overall Study Withdrawal by Subject	2	1	0

Baseline Characteristics

Study of LAU-7b for the Treatment of Long COVID in Adults

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	LAU-7b for 3 Cycles (Arm 1, AAA) n=91 Participants Three cycles of 14 days of once-a-day intake of LAU-7b, each followed by a treatment intake pause of 14 days.	LAU-7b for 1 Cycle, Then Placebo (Arm 2, APP) n=91 Participants One cycle of 14 days of once-a-day intake of LAU-7b followed by two cycles of 14 days of placebo administered similarly, each followed by a treatment intake pause of 14 days.	Placebo for 3 Cycles (Arm 3, PPP) n=90 Participants Three cycles of 14 days of once-a-day intake of placebo, each followed by a treatment intake pause of 14 days	Total n=272 Participants Total of all reporting groups
Age, Continuous	49.9 years STANDARD_DEVIATION 9.26 • n=9 Participants	46.8 years STANDARD_DEVIATION 10.96 • n=6 Participants	46.5 years STANDARD_DEVIATION 10.08 • n=9 Participants	47.8 years STANDARD_DEVIATION 10.20 • n=205 Participants
Age, Customized Age categories · 18 to 44 years	24 Participants n=9 Participants	40 Participants n=6 Participants	37 Participants n=9 Participants	101 Participants n=205 Participants
Age, Customized Age categories · 45 to 54 years	39 Participants n=9 Participants	33 Participants n=6 Participants	34 Participants n=9 Participants	106 Participants n=205 Participants
Age, Customized Age categories · Equal or greater than 55 years	28 Participants n=9 Participants	18 Participants n=6 Participants	19 Participants n=9 Participants	65 Participants n=205 Participants
Sex: Female, Male Female	76 Participants n=9 Participants	78 Participants n=6 Participants	74 Participants n=9 Participants	228 Participants n=205 Participants
Sex: Female, Male Male	15 Participants n=9 Participants	13 Participants n=6 Participants	16 Participants n=9 Participants	44 Participants n=205 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=9 Participants	2 Participants n=6 Participants	2 Participants n=9 Participants	4 Participants n=205 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	91 Participants n=9 Participants	89 Participants n=6 Participants	88 Participants n=9 Participants	268 Participants n=205 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=9 Participants	0 Participants n=6 Participants	0 Participants n=9 Participants	0 Participants n=205 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=9 Participants	0 Participants n=6 Participants	0 Participants n=9 Participants	0 Participants n=205 Participants
Race (NIH/OMB) Asian	0 Participants n=9 Participants	0 Participants n=6 Participants	1 Participants n=9 Participants	1 Participants n=205 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=9 Participants	0 Participants n=6 Participants	0 Participants n=9 Participants	0 Participants n=205 Participants
Race (NIH/OMB) Black or African American	0 Participants n=9 Participants	1 Participants n=6 Participants	0 Participants n=9 Participants	1 Participants n=205 Participants
Race (NIH/OMB) White	90 Participants n=9 Participants	90 Participants n=6 Participants	89 Participants n=9 Participants	269 Participants n=205 Participants
Race (NIH/OMB) More than one race	0 Participants n=9 Participants	0 Participants n=6 Participants	0 Participants n=9 Participants	0 Participants n=205 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=9 Participants	0 Participants n=6 Participants	0 Participants n=9 Participants	1 Participants n=205 Participants
Region of Enrollment Canada	91 participants n=9 Participants	91 participants n=6 Participants	90 participants n=9 Participants	272 participants n=205 Participants
Body Weight	77.18 kilograms STANDARD_DEVIATION 18.972 • n=9 Participants	75.98 kilograms STANDARD_DEVIATION 17.375 • n=6 Participants	81.88 kilograms STANDARD_DEVIATION 23.682 • n=9 Participants	78.34 kilograms STANDARD_DEVIATION 20.264 • n=205 Participants
Body Mass Index (BMI)	28.14 kilograms/square meter STANDARD_DEVIATION 7.07 • n=9 Participants	27.91 kilograms/square meter STANDARD_DEVIATION 6.29 • n=6 Participants	29.54 kilograms/square meter STANDARD_DEVIATION 7.82 • n=9 Participants	28.53 kilograms/square meter STANDARD_DEVIATION 7.10 • n=205 Participants
Vaccinated against Coronavirus Disease 2019 (COVID-19) Vaccinated	87 Participants n=9 Participants	81 Participants n=6 Participants	85 Participants n=9 Participants	253 Participants n=205 Participants
Vaccinated against Coronavirus Disease 2019 (COVID-19) Non-vaccinated	4 Participants n=9 Participants	10 Participants n=6 Participants	5 Participants n=9 Participants	19 Participants n=205 Participants

PRIMARY outcome

Timeframe: Week 0 and 12

Population: Intent-to-Treat (ITT) population

The SF-36 questionnaire consists of 36 items grouped in eight health domains, vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health, that can be aggregated to two summary scales, physical component summary (PCS ) and mental component summary (MCS). The PCS summarizes the physical status and constitutes the primary outcome variable. Each health domain score consists of the sum scores of the assigned questions. Scores are weighted and transformed into a scale ranging from 0 (greatest possible health restrictions, ie, severe disability) to 100 (no health restrictions). A higher score means a better physical status. The calculation process for the PCS has been previously described by Taft et al. 2001.

Outcome measures

Outcome measures
Measure	Placebo for 3 Cycles (Arm 3, PPP) n=90 Participants Three cycles of 14 days of once-a-day intake of placebo, each followed by a treatment intake pause of 14 days	LAU-7b for 3 Cycles (Arm 1, AAA) n=91 Participants Three cycles of 14 days of once-a-day intake of LAU-7b, each followed by a treatment intake pause of 14 days.	LAU-7b for 1 Cycle, Then Placebo (Arm 2, APP) n=91 Participants One cycle of 14 days of once-a-day intake of LAU-7b followed by two cycles of 14 days of placebo administered similarly, each followed by a treatment intake pause of 14 days.
Change From Baseline in Physical Component Summary (PCS) of the Medical Outcomes Study Short-Form-36 (SF-36) at Week 12 PCS at Week 12	30.06 score on a scale Standard Deviation 9.484	29.47 score on a scale Standard Deviation 9.267	29.90 score on a scale Standard Deviation 7.941
Change From Baseline in Physical Component Summary (PCS) of the Medical Outcomes Study Short-Form-36 (SF-36) at Week 12 Change from Baseline PCS	2.78 score on a scale Standard Deviation 8.298	1.94 score on a scale Standard Deviation 8.034	3.32 score on a scale Standard Deviation 7.777

SECONDARY outcome

Timeframe: From Week 0 to Week 12

Population: Safety population includes all participants who received at least one dose of study treatment.

Number of participants with adverse events. The safety was assessed through the monitoring of adverse events including laboratory test abnormalities, serious adverse events and adverse events leading to study treatment discontinuation. Treatment-emergent adverse event is defined as any adverse event with onset date on or after the first dose of study drug and on or before the Week 12 in person follow-up or until early termination or death, whichever occurred first.

Outcome measures

Outcome measures
Measure	Placebo for 3 Cycles (Arm 3, PPP) n=90 Participants Three cycles of 14 days of once-a-day intake of placebo, each followed by a treatment intake pause of 14 days	LAU-7b for 3 Cycles (Arm 1, AAA) n=90 Participants Three cycles of 14 days of once-a-day intake of LAU-7b, each followed by a treatment intake pause of 14 days.	LAU-7b for 1 Cycle, Then Placebo (Arm 2, APP) n=91 Participants One cycle of 14 days of once-a-day intake of LAU-7b followed by two cycles of 14 days of placebo administered similarly, each followed by a treatment intake pause of 14 days.
Safety of LAU-7b, Overview Participants with serious treatment-emergent adverse events	2 participants	1 participants	2 participants
Safety of LAU-7b, Overview Participants with treatment-emergent adverse events	61 participants	71 participants	71 participants
Safety of LAU-7b, Overview Participants with treatment-emergent adverse events leading to treatment discontinuation	1 participants	7 participants	0 participants
Safety of LAU-7b, Overview Participants with treatment-emergent adverse events with fatal outcome	0 participants	0 participants	0 participants
Safety of LAU-7b, Overview Participants with suspected unexpected serious adverse reaction (SUSAR)	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Weeks 4, 8 and 12

Population: ITT population

The PGI-C is a single item questionnaire that asks: "Overall, how would you rate the change in your ability to perform usual daily activities since you started the study?". These are the 7-point scale options: 1) "very much better", 2) "much better", 3) "minimally better", 4) "no change", 5) "minimally worse", 6) "much worse", or 7) "very much worse". Higher scores indicate a change for the worse and lower scores indicate a change for the better.

Outcome measures

Outcome measures
Measure	Placebo for 3 Cycles (Arm 3, PPP) n=90 Participants Three cycles of 14 days of once-a-day intake of placebo, each followed by a treatment intake pause of 14 days	LAU-7b for 3 Cycles (Arm 1, AAA) n=91 Participants Three cycles of 14 days of once-a-day intake of LAU-7b, each followed by a treatment intake pause of 14 days.	LAU-7b for 1 Cycle, Then Placebo (Arm 2, APP) n=91 Participants One cycle of 14 days of once-a-day intake of LAU-7b followed by two cycles of 14 days of placebo administered similarly, each followed by a treatment intake pause of 14 days.
Patient Global Impression of Change (PGI-C) PGI-C at Week 4 · Very much improved	1 Participants	0 Participants	1 Participants
Patient Global Impression of Change (PGI-C) PGI-C at Week 4 · Much improved	3 Participants	10 Participants	3 Participants
Patient Global Impression of Change (PGI-C) PGI-C at Week 4 · Minimally worse	6 Participants	6 Participants	7 Participants
Patient Global Impression of Change (PGI-C) PGI-C at Week 8 · Minimally improved	32 Participants	23 Participants	28 Participants
Patient Global Impression of Change (PGI-C) PGI-C at Week 4 · Minimally improved	25 Participants	25 Participants	25 Participants
Patient Global Impression of Change (PGI-C) PGI-C at Week 4 · No change	47 Participants	43 Participants	46 Participants
Patient Global Impression of Change (PGI-C) PGI-C at Week 4 · Much worse	1 Participants	2 Participants	3 Participants
Patient Global Impression of Change (PGI-C) PGI-C at Week 4 · Very much worse	2 Participants	1 Participants	3 Participants
Patient Global Impression of Change (PGI-C) PGI-C at Week 8 · Very much improved	3 Participants	3 Participants	0 Participants
Patient Global Impression of Change (PGI-C) PGI-C at Week 8 · Much improved	1 Participants	11 Participants	5 Participants
Patient Global Impression of Change (PGI-C) PGI-C at Week 8 · No change	35 Participants	39 Participants	42 Participants
Patient Global Impression of Change (PGI-C) PGI-C at Week 8 · Minimally worse	10 Participants	8 Participants	8 Participants
Patient Global Impression of Change (PGI-C) PGI-C at Week 8 · Much worse	3 Participants	2 Participants	6 Participants
Patient Global Impression of Change (PGI-C) PGI-C at Week 8 · Very much worse	1 Participants	1 Participants	0 Participants
Patient Global Impression of Change (PGI-C) PGI-C at Week 12 · Very much improved	2 Participants	7 Participants	0 Participants
Patient Global Impression of Change (PGI-C) PGI-C at Week 12 · Much improved	13 Participants	9 Participants	5 Participants
Patient Global Impression of Change (PGI-C) PGI-C at Week 12 · Minimally improved	30 Participants	18 Participants	37 Participants
Patient Global Impression of Change (PGI-C) PGI-C at Week 12 · No change	29 Participants	43 Participants	38 Participants
Patient Global Impression of Change (PGI-C) PGI-C at Week 12 · Minimally worse	11 Participants	8 Participants	5 Participants
Patient Global Impression of Change (PGI-C) PGI-C at Week 12 · Much worse	4 Participants	2 Participants	5 Participants
Patient Global Impression of Change (PGI-C) PGI-C at Week 12 · Very much worse	1 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Weeks 4, 8 and 12

Population: ITT population

Marked improvement includes "Very much improved" and Much improved". The PGI-C is a single item questionnaire that asks: "Overall, how would you rate the change in your ability to perform usual daily activities since you started the study?". These are the 7-point scale options: 1) "very much better", 2) "much better", 3) "minimally better", 4) "no change", 5) "minimally worse", 6) "much worse", or 7) "very much worse". Higher scores indicate a change for the worse and lower scores indicate a change for the better.

Outcome measures

Outcome measures
Measure	Placebo for 3 Cycles (Arm 3, PPP) n=90 Participants Three cycles of 14 days of once-a-day intake of placebo, each followed by a treatment intake pause of 14 days	LAU-7b for 3 Cycles (Arm 1, AAA) n=91 Participants Three cycles of 14 days of once-a-day intake of LAU-7b, each followed by a treatment intake pause of 14 days.	LAU-7b for 1 Cycle, Then Placebo (Arm 2, APP) n=91 Participants One cycle of 14 days of once-a-day intake of LAU-7b followed by two cycles of 14 days of placebo administered similarly, each followed by a treatment intake pause of 14 days.
Proportion of Participants With Marked Improvement in PGI-C Marked improvement of PGI-C at Week 4 · Participants achieving a marked improvement	4 Participants	10 Participants	4 Participants
Proportion of Participants With Marked Improvement in PGI-C Marked improvement of PGI-C at Week 4 · No marked improvement	81 Participants	77 Participants	84 Participants
Proportion of Participants With Marked Improvement in PGI-C Marked improvement of PGI-C at Week 8 · Participants achieving a marked improvement	4 Participants	14 Participants	5 Participants
Proportion of Participants With Marked Improvement in PGI-C Marked improvement of PGI-C at Week 8 · No marked improvement	81 Participants	73 Participants	84 Participants
Proportion of Participants With Marked Improvement in PGI-C Marked improvement of PGI-C at Week 12 · Participants achieving a marked improvement	15 Participants	16 Participants	5 Participants
Proportion of Participants With Marked Improvement in PGI-C Marked improvement of PGI-C at Week 12 · No marked improvement	75 Participants	72 Participants	85 Participants

SECONDARY outcome

Timeframe: Weeks 0, 4, 8 and 12

Population: ITT population

This instrument was developed to characterize fatigue, in cancer and used in other conditions with a phenotype of fatigue. It is a 13-item measure that assesses self-reported fatigue and its impact upon daily activities and function. The recall period is 7 days and the response scale employs a 5-point Likert-type scale. The final total score is the sum of the responses for all 13 items and can range from 0 to 52. A higher score means less fatigue.

Outcome measures

Outcome measures
Measure	Placebo for 3 Cycles (Arm 3, PPP) n=90 Participants Three cycles of 14 days of once-a-day intake of placebo, each followed by a treatment intake pause of 14 days	LAU-7b for 3 Cycles (Arm 1, AAA) n=91 Participants Three cycles of 14 days of once-a-day intake of LAU-7b, each followed by a treatment intake pause of 14 days.	LAU-7b for 1 Cycle, Then Placebo (Arm 2, APP) n=91 Participants One cycle of 14 days of once-a-day intake of LAU-7b followed by two cycles of 14 days of placebo administered similarly, each followed by a treatment intake pause of 14 days.
Change From Baseline in the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Scale Change from baseline at Week 4	2.91 units on a scale Standard Deviation 8.103	4.70 units on a scale Standard Deviation 8.535	2.67 units on a scale Standard Deviation 7.005
Change From Baseline in the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Scale Value at Week 12	22.19 units on a scale Standard Deviation 11.082	20.63 units on a scale Standard Deviation 11.914	19.07 units on a scale Standard Deviation 9.547
Change From Baseline in the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Scale Change from baseline at Week 12	5.73 units on a scale Standard Deviation 10.749	5.07 units on a scale Standard Deviation 8.507	4.07 units on a scale Standard Deviation 7.998
Change From Baseline in the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Scale Value at baseline	16.48 units on a scale Standard Deviation 8.456	15.68 units on a scale Standard Deviation 8.141	15.18 units on a scale Standard Deviation 6.940
Change From Baseline in the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Scale Value at Week 4	19.33 units on a scale Standard Deviation 9.930	20.28 units on a scale Standard Deviation 11.524	17.77 units on a scale Standard Deviation 9.499
Change From Baseline in the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Scale Value at Week 8	19.60 units on a scale Standard Deviation 10.140	21.67 units on a scale Standard Deviation 12.426	18.20 units on a scale Standard Deviation 9.309
Change From Baseline in the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Scale Change from baseline at Week 8	3.29 units on a scale Standard Deviation 9.057	5.94 units on a scale Standard Deviation 8.535	3.14 units on a scale Standard Deviation 8.099

SECONDARY outcome

Timeframe: Weeks 0 and 12

Population: ITT population

This instrument was developed to characterize and evaluate the debilitation caused by a physical exertion, whether a usual daily activity or a leisure activity. It is a 10-item questionnaire that assess both the nature of post-exertional malaise (PEM) and duration of symptom. In this study, the presence or not of PEM (based on frequency and severity of 5 PEM items) is determined by the questionnaire. The endpoint of the study is the proportion of participants with PEM at baseline and Week 12, compared between treatment groups.

Outcome measures

Outcome measures
Measure	Placebo for 3 Cycles (Arm 3, PPP) n=90 Participants Three cycles of 14 days of once-a-day intake of placebo, each followed by a treatment intake pause of 14 days	LAU-7b for 3 Cycles (Arm 1, AAA) n=91 Participants Three cycles of 14 days of once-a-day intake of LAU-7b, each followed by a treatment intake pause of 14 days.	LAU-7b for 1 Cycle, Then Placebo (Arm 2, APP) n=91 Participants One cycle of 14 days of once-a-day intake of LAU-7b followed by two cycles of 14 days of placebo administered similarly, each followed by a treatment intake pause of 14 days.
Change From Baseline in the DePaul Post-Exertional Malaise Questionnaire (DPEMQ) Baseline · Participants with PEM	84 Participants	81 Participants	87 Participants
Change From Baseline in the DePaul Post-Exertional Malaise Questionnaire (DPEMQ) Week 12 · Participants without PEM	7 Participants	7 Participants	8 Participants
Change From Baseline in the DePaul Post-Exertional Malaise Questionnaire (DPEMQ) Baseline · Participants without PEM	6 Participants	7 Participants	3 Participants
Change From Baseline in the DePaul Post-Exertional Malaise Questionnaire (DPEMQ) Week 12 · Participants with PEM	83 Participants	80 Participants	82 Participants

SECONDARY outcome

Timeframe: Weeks 0, 4 and 8

Population: ITT population

The SF-36 questionnaire consists of 36 items grouped in eight health domains, vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health, that can be aggregated to two summary scales, physical component summary (PCS ) and mental component summary (MCS). The PCS summarizes the physical status and constitutes the primary outcome variable. Each health domain score consists of the sum scores of the assigned questions. Scores are weighted and transformed into a scale ranging from 0 (greatest possible health restrictions, ie, severe disability) to 100 (no health restrictions). A higher score means a better physical status. The calculation process for the PCS has been previously described by Taft et al. 2001. The analysis is performed jointly with the primary outcome measure (Week 12). A positive change from baseline value means improvement, negative value means worsening.

Outcome measures

Outcome measures
Measure	Placebo for 3 Cycles (Arm 3, PPP) n=90 Participants Three cycles of 14 days of once-a-day intake of placebo, each followed by a treatment intake pause of 14 days	LAU-7b for 3 Cycles (Arm 1, AAA) n=91 Participants Three cycles of 14 days of once-a-day intake of LAU-7b, each followed by a treatment intake pause of 14 days.	LAU-7b for 1 Cycle, Then Placebo (Arm 2, APP) n=91 Participants One cycle of 14 days of once-a-day intake of LAU-7b followed by two cycles of 14 days of placebo administered similarly, each followed by a treatment intake pause of 14 days.
Change From Baseline in Physical Component Summary (PCS) of the Medical Outcomes Study Short-Form-36 (SF-36) at Weeks 4 and 8 Change from baseline PCS at Week 4	1.05 units on a scale Standard Deviation 7.661	1.26 units on a scale Standard Deviation 6.950	2.89 units on a scale Standard Deviation 7.514
Change From Baseline in Physical Component Summary (PCS) of the Medical Outcomes Study Short-Form-36 (SF-36) at Weeks 4 and 8 PCS at Week 8	29.64 units on a scale Standard Deviation 9.051	30.35 units on a scale Standard Deviation 9.333	29.39 units on a scale Standard Deviation 8.295
Change From Baseline in Physical Component Summary (PCS) of the Medical Outcomes Study Short-Form-36 (SF-36) at Weeks 4 and 8 Change from baseline PCS at Week 8	2.28 units on a scale Standard Deviation 7.897	2.64 units on a scale Standard Deviation 8.806	2.81 units on a scale Standard Deviation 7.117
Change From Baseline in Physical Component Summary (PCS) of the Medical Outcomes Study Short-Form-36 (SF-36) at Weeks 4 and 8 PCS at Week 4	28.20 units on a scale Standard Deviation 8.767	28.71 units on a scale Standard Deviation 6.934	29.18 units on a scale Standard Deviation 8.350

SECONDARY outcome

Timeframe: Weeks 0, 4, 8 and 12

Population: ITT population

The SF-36 questionnaire consists of 36 items grouped in eight health domains, vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health, that can be aggregated to two summary scales, physical component summary (PCS ) and mental component summary (MCS). Scores are weighted and transformed into a scale ranging from 0 (greatest possible health restrictions, ie, severe disability) to 100 (no health restrictions). A higher score means a better outcome. The study endpoint is the change from baseline in score, a positive change from baseline value means improvement and a negative value means worsening outcome. For sake of conciseness, only Week 12 comparisons are presented.

Outcome measures

Outcome measures
Measure	Placebo for 3 Cycles (Arm 3, PPP) n=90 Participants Three cycles of 14 days of once-a-day intake of placebo, each followed by a treatment intake pause of 14 days	LAU-7b for 3 Cycles (Arm 1, AAA) n=91 Participants Three cycles of 14 days of once-a-day intake of LAU-7b, each followed by a treatment intake pause of 14 days.	LAU-7b for 1 Cycle, Then Placebo (Arm 2, APP) n=91 Participants One cycle of 14 days of once-a-day intake of LAU-7b followed by two cycles of 14 days of placebo administered similarly, each followed by a treatment intake pause of 14 days.
Change From Baseline in the Other Aspects (Domain Scales) Than the PCS of the Medical Outcomes Study Short-Form-36 (SF-36) Change from baseline vitality score at Week 4	3.9 units on a scale Standard Deviation 15.38	7.6 units on a scale Standard Deviation 16.64	7.2 units on a scale Standard Deviation 14.61
Change From Baseline in the Other Aspects (Domain Scales) Than the PCS of the Medical Outcomes Study Short-Form-36 (SF-36) Change from baseline bodily pain score at Week 4	3.7 units on a scale Standard Deviation 15.09	2.4 units on a scale Standard Deviation 20.50	0.4 units on a scale Standard Deviation 21.16
Change From Baseline in the Other Aspects (Domain Scales) Than the PCS of the Medical Outcomes Study Short-Form-36 (SF-36) Change from baseline general health perception score at Week 8	1.2 units on a scale Standard Deviation 13.05	5.1 units on a scale Standard Deviation 13.85	1.9 units on a scale Standard Deviation 11.66
Change From Baseline in the Other Aspects (Domain Scales) Than the PCS of the Medical Outcomes Study Short-Form-36 (SF-36) Change from baseline general health perception score at Week 12	2.3 units on a scale Standard Deviation 14.61	5.4 units on a scale Standard Deviation 14.57	3.4 units on a scale Standard Deviation 13.33
Change From Baseline in the Other Aspects (Domain Scales) Than the PCS of the Medical Outcomes Study Short-Form-36 (SF-36) Change from baseline physical role functioning score at Week 4	3.0 units on a scale Standard Deviation 23.37	3.0 units on a scale Standard Deviation 17.20	4.5 units on a scale Standard Deviation 16.99
Change From Baseline in the Other Aspects (Domain Scales) Than the PCS of the Medical Outcomes Study Short-Form-36 (SF-36) Change from baseline physical role functioning score at Week 8	6.4 units on a scale Standard Deviation 26.30	7.5 units on a scale Standard Deviation 23.01	5.0 units on a scale Standard Deviation 18.82
Change From Baseline in the Other Aspects (Domain Scales) Than the PCS of the Medical Outcomes Study Short-Form-36 (SF-36) Baseline emotional role functioning	51.5 units on a scale Standard Deviation 44.61	47.0 units on a scale Standard Deviation 45.38	55.8 units on a scale Standard Deviation 46.00
Change From Baseline in the Other Aspects (Domain Scales) Than the PCS of the Medical Outcomes Study Short-Form-36 (SF-36) Change from baseline emotional role functioning score at Week 8	-0.4 units on a scale Standard Deviation 44.90	6.4 units on a scale Standard Deviation 49.79	-6.7 units on a scale Standard Deviation 46.80
Change From Baseline in the Other Aspects (Domain Scales) Than the PCS of the Medical Outcomes Study Short-Form-36 (SF-36) Change from baseline emotional role functioning score at Week 12	6.9 units on a scale Standard Deviation 43.37	1.6 units on a scale Standard Deviation 48.50	-6.6 units on a scale Standard Deviation 43.93
Change From Baseline in the Other Aspects (Domain Scales) Than the PCS of the Medical Outcomes Study Short-Form-36 (SF-36) Baseline social role functioning score	26.6 units on a scale Standard Deviation 19.68	23.9 units on a scale Standard Deviation 19.66	23.3 units on a scale Standard Deviation 19.06
Change From Baseline in the Other Aspects (Domain Scales) Than the PCS of the Medical Outcomes Study Short-Form-36 (SF-36) Change from baseline social role functioning score at Week 4	4.4 units on a scale Standard Deviation 16.82	5.6 units on a scale Standard Deviation 18.95	3.9 units on a scale Standard Deviation 17.56
Change From Baseline in the Other Aspects (Domain Scales) Than the PCS of the Medical Outcomes Study Short-Form-36 (SF-36) Change from baseline social role functioning score at Week 12	9.3 units on a scale Standard Deviation 23.75	10.4 units on a scale Standard Deviation 21.12	7.6 units on a scale Standard Deviation 20.15
Change From Baseline in the Other Aspects (Domain Scales) Than the PCS of the Medical Outcomes Study Short-Form-36 (SF-36) Change from baseline mental health score at Week 12	-0.1 units on a scale Standard Deviation 7.92	1.0 units on a scale Standard Deviation 7.66	-0.0 units on a scale Standard Deviation 8.45
Change From Baseline in the Other Aspects (Domain Scales) Than the PCS of the Medical Outcomes Study Short-Form-36 (SF-36) Baseline vitality score	18.8 units on a scale Standard Deviation 14.61	17.6 units on a scale Standard Deviation 14.36	14.8 units on a scale Standard Deviation 12.55
Change From Baseline in the Other Aspects (Domain Scales) Than the PCS of the Medical Outcomes Study Short-Form-36 (SF-36) Change from baseline vitality score at Week 8	6.2 units on a scale Standard Deviation 18.54	10.6 units on a scale Standard Deviation 18.25	5.8 units on a scale Standard Deviation 14.74
Change From Baseline in the Other Aspects (Domain Scales) Than the PCS of the Medical Outcomes Study Short-Form-36 (SF-36) Change from baseline vitality score at Week 12	7.8 units on a scale Standard Deviation 19.64	7.1 units on a scale Standard Deviation 17.78	6.9 units on a scale Standard Deviation 14.23
Change From Baseline in the Other Aspects (Domain Scales) Than the PCS of the Medical Outcomes Study Short-Form-36 (SF-36) Baseline physical functioning score	41.6 units on a scale Standard Deviation 23.68	42.8 units on a scale Standard Deviation 22.85	38.1 units on a scale Standard Deviation 20.55
Change From Baseline in the Other Aspects (Domain Scales) Than the PCS of the Medical Outcomes Study Short-Form-36 (SF-36) Change from baseline physical functioning score at Week 4	-1.7 units on a scale Standard Deviation 22.09	-0.5 units on a scale Standard Deviation 21.19	5.8 units on a scale Standard Deviation 21.36
Change From Baseline in the Other Aspects (Domain Scales) Than the PCS of the Medical Outcomes Study Short-Form-36 (SF-36) Change from baseline physical functioning score at Week 8	2.2 units on a scale Standard Deviation 25.05	3.9 units on a scale Standard Deviation 24.65	4.8 units on a scale Standard Deviation 23.31
Change From Baseline in the Other Aspects (Domain Scales) Than the PCS of the Medical Outcomes Study Short-Form-36 (SF-36) Change from baseline physical functioning score at Week 12	4.6 units on a scale Standard Deviation 25.69	3.1 units on a scale Standard Deviation 26.71	8.0 units on a scale Standard Deviation 26.95
Change From Baseline in the Other Aspects (Domain Scales) Than the PCS of the Medical Outcomes Study Short-Form-36 (SF-36) Baseline bodily pain score	35.3 units on a scale Standard Deviation 22.04	35.7 units on a scale Standard Deviation 24.45	37.5 units on a scale Standard Deviation 23.44
Change From Baseline in the Other Aspects (Domain Scales) Than the PCS of the Medical Outcomes Study Short-Form-36 (SF-36) Change from baseline bodily pain score at Week 8	6.3 units on a scale Standard Deviation 17.94	6.2 units on a scale Standard Deviation 19.87	3.0 units on a scale Standard Deviation 20.85
Change From Baseline in the Other Aspects (Domain Scales) Than the PCS of the Medical Outcomes Study Short-Form-36 (SF-36) Change from baseline bodily pain score at Week 12	12.0 units on a scale Standard Deviation 24.68	4.1 units on a scale Standard Deviation 18.92	4.2 units on a scale Standard Deviation 18.35
Change From Baseline in the Other Aspects (Domain Scales) Than the PCS of the Medical Outcomes Study Short-Form-36 (SF-36) Baseline general health perception score	31.8 units on a scale Standard Deviation 16.65	30.0 units on a scale Standard Deviation 15.80	31.4 units on a scale Standard Deviation 14.96
Change From Baseline in the Other Aspects (Domain Scales) Than the PCS of the Medical Outcomes Study Short-Form-36 (SF-36) Change from baseline general health perception score at Week 4	0.8 units on a scale Standard Deviation 12.45	3.6 units on a scale Standard Deviation 11.85	2.0 units on a scale Standard Deviation 11.20
Change From Baseline in the Other Aspects (Domain Scales) Than the PCS of the Medical Outcomes Study Short-Form-36 (SF-36) Baseline physical role functioning score	3.7 units on a scale Standard Deviation 14.45	1.7 units on a scale Standard Deviation 8.30	0.8 units on a scale Standard Deviation 4.54
Change From Baseline in the Other Aspects (Domain Scales) Than the PCS of the Medical Outcomes Study Short-Form-36 (SF-36) Change from baseline physical role functioning score at Week 12	4.3 units on a scale Standard Deviation 20.95	2.9 units on a scale Standard Deviation 17.00	2.3 units on a scale Standard Deviation 11.90
Change From Baseline in the Other Aspects (Domain Scales) Than the PCS of the Medical Outcomes Study Short-Form-36 (SF-36) Change from baseline emotional role functioning score at Week 4	-5.3 units on a scale Standard Deviation 38.66	-2.4 units on a scale Standard Deviation 44.41	-10.3 units on a scale Standard Deviation 45.40
Change From Baseline in the Other Aspects (Domain Scales) Than the PCS of the Medical Outcomes Study Short-Form-36 (SF-36) Change from baseline social role functioning score at Week 8	7.2 units on a scale Standard Deviation 19.15	10.4 units on a scale Standard Deviation 20.08	5.4 units on a scale Standard Deviation 18.94
Change From Baseline in the Other Aspects (Domain Scales) Than the PCS of the Medical Outcomes Study Short-Form-36 (SF-36) Baseline mental health score	56.2 units on a scale Standard Deviation 8.05	55.7 units on a scale Standard Deviation 6.28	56.1 units on a scale Standard Deviation 8.11
Change From Baseline in the Other Aspects (Domain Scales) Than the PCS of the Medical Outcomes Study Short-Form-36 (SF-36) Change from baseline mental health score at Week 4	1.3 units on a scale Standard Deviation 7.98	1.0 units on a scale Standard Deviation 7.04	-0.2 units on a scale Standard Deviation 7.62
Change From Baseline in the Other Aspects (Domain Scales) Than the PCS of the Medical Outcomes Study Short-Form-36 (SF-36) Change from baseline mental health score at Week 8	0.7 units on a scale Standard Deviation 7.09	0.7 units on a scale Standard Deviation 6.89	-0.2 units on a scale Standard Deviation 7.40

SECONDARY outcome

Timeframe: From Week 0 through Weeks 4, 8 and 12

Population: ITT population

This will be assessed by a single question with either yes or no as answer: "Do you judge that you have regained the daily usual activity level you had prior to being infected by COVID-19 back in Month xxxx? By daily usual activity we mean work, leisure, physical exercise...etc."

Outcome measures

Outcome measures
Measure	Placebo for 3 Cycles (Arm 3, PPP) n=90 Participants Three cycles of 14 days of once-a-day intake of placebo, each followed by a treatment intake pause of 14 days	LAU-7b for 3 Cycles (Arm 1, AAA) n=91 Participants Three cycles of 14 days of once-a-day intake of LAU-7b, each followed by a treatment intake pause of 14 days.	LAU-7b for 1 Cycle, Then Placebo (Arm 2, APP) n=91 Participants One cycle of 14 days of once-a-day intake of LAU-7b followed by two cycles of 14 days of placebo administered similarly, each followed by a treatment intake pause of 14 days.
Proportion of Subjects Who Judge to Have Regained Their Daily Usual Activity Level of Pre-causative-infection. Week 4 · Participants who judge to have regained daily usual activity level	0 Participants	0 Participants	3 Participants
Proportion of Subjects Who Judge to Have Regained Their Daily Usual Activity Level of Pre-causative-infection. Week 4 · Participants who judge NOT to have regained daily usual activity level	90 Participants	89 Participants	88 Participants
Proportion of Subjects Who Judge to Have Regained Their Daily Usual Activity Level of Pre-causative-infection. Week 8 · Participants who judge NOT to have regained daily usual activity level	89 Participants	88 Participants	90 Participants
Proportion of Subjects Who Judge to Have Regained Their Daily Usual Activity Level of Pre-causative-infection. Week 12 · Participants who judge to have regained daily usual activity level	2 Participants	0 Participants	1 Participants
Proportion of Subjects Who Judge to Have Regained Their Daily Usual Activity Level of Pre-causative-infection. Week 8 · Participants who judge to have regained daily usual activity level	1 Participants	0 Participants	0 Participants
Proportion of Subjects Who Judge to Have Regained Their Daily Usual Activity Level of Pre-causative-infection. Week 12 · Participants who judge NOT to have regained daily usual activity level	88 Participants	88 Participants	89 Participants

SECONDARY outcome

Timeframe: Weeks 4, 8 and 12

Population: ITT population

The Core (most common) Long COVID symptoms are: fatigue, trouble sleeping, shortness of breath, general pain and discomfort, cognitive problems (most commonly known as brain fog or memory fog) and mental health symptoms. Each symptom is rated as: 0=No symptom, 1=Mild symptom (no interference with daily activities), 2=Moderate symptom (interfere and may limit daily activities), and 3=Severe symptom (strong interference preventing daily activities. The higher the rating is, worse is the symptom. 0 and 1 are deemed not burdensome, 2 and 3 are burdensome. A sum of the burdensome category is calculated for each visit and is the endpoint being evaluated for improvement since burdensome symptoms are those with highest impact on daily usual activity level.

Outcome measures

Outcome measures
Measure	Placebo for 3 Cycles (Arm 3, PPP) n=90 Participants Three cycles of 14 days of once-a-day intake of placebo, each followed by a treatment intake pause of 14 days	LAU-7b for 3 Cycles (Arm 1, AAA) n=91 Participants Three cycles of 14 days of once-a-day intake of LAU-7b, each followed by a treatment intake pause of 14 days.	LAU-7b for 1 Cycle, Then Placebo (Arm 2, APP) n=91 Participants One cycle of 14 days of once-a-day intake of LAU-7b followed by two cycles of 14 days of placebo administered similarly, each followed by a treatment intake pause of 14 days.
Proportion of Subjects Achieving >=25% (>=50% and >=75% Presented Separately) Improvement in the Sum of Individual Core Long COVID Symptom Severity as Evaluated by a Standard 4-level Likert Scale. Week 4 · Participants not reaching 25% improvement in burdensome symptoms total score	84 Participants	79 Participants	84 Participants
Proportion of Subjects Achieving >=25% (>=50% and >=75% Presented Separately) Improvement in the Sum of Individual Core Long COVID Symptom Severity as Evaluated by a Standard 4-level Likert Scale. Week 8 · Participants with at least 25% improvement in burdensome symptoms total score	7 Participants	15 Participants	18 Participants
Proportion of Subjects Achieving >=25% (>=50% and >=75% Presented Separately) Improvement in the Sum of Individual Core Long COVID Symptom Severity as Evaluated by a Standard 4-level Likert Scale. Week 12 · Participants not reaching 25% improvement in burdensome symptoms total score	70 Participants	70 Participants	73 Participants
Proportion of Subjects Achieving >=25% (>=50% and >=75% Presented Separately) Improvement in the Sum of Individual Core Long COVID Symptom Severity as Evaluated by a Standard 4-level Likert Scale. Week 4 · Participants with at least 25% improvement in burdensome symptoms total score	6 Participants	10 Participants	6 Participants
Proportion of Subjects Achieving >=25% (>=50% and >=75% Presented Separately) Improvement in the Sum of Individual Core Long COVID Symptom Severity as Evaluated by a Standard 4-level Likert Scale. Week 8 · Participants not reaching 25% improvement in burdensome symptoms total score	81 Participants	68 Participants	72 Participants
Proportion of Subjects Achieving >=25% (>=50% and >=75% Presented Separately) Improvement in the Sum of Individual Core Long COVID Symptom Severity as Evaluated by a Standard 4-level Likert Scale. Week 12 · Participants with at least 25% improvement in burdensome symptoms total score	18 Participants	15 Participants	16 Participants

SECONDARY outcome

Timeframe: Weeks 4, 8 and 12

Population: ITT population

The Core (most common) Long COVID symptoms are: fatigue, trouble sleeping, shortness of breath, general pain and discomfort, cognitive problems (most commonly known as brain fog or memory fog) and mental health symptoms. Each symptom is rated as: 0=No symptom, 1=Mild symptom (no interference with daily activities), 2=Moderate symptom (interfere and may limit daily activities), and 3=Severe symptom (strong interference preventing daily activities. The higher the rating is, worse is the symptom. 0 and 1 are deemed not burdensome, 2 and 3 are burdensome. A sum of the burdensome category is calculated for each visit and is the endpoint being evaluated for improvement since burdensome symptoms are those with highest impact on daily usual activity level.

Outcome measures

Outcome measures
Measure	Placebo for 3 Cycles (Arm 3, PPP) n=90 Participants Three cycles of 14 days of once-a-day intake of placebo, each followed by a treatment intake pause of 14 days	LAU-7b for 3 Cycles (Arm 1, AAA) n=91 Participants Three cycles of 14 days of once-a-day intake of LAU-7b, each followed by a treatment intake pause of 14 days.	LAU-7b for 1 Cycle, Then Placebo (Arm 2, APP) n=91 Participants One cycle of 14 days of once-a-day intake of LAU-7b followed by two cycles of 14 days of placebo administered similarly, each followed by a treatment intake pause of 14 days.
Proportion of Subjects Achieving >=50% (>=25% and >=75% Presented Separately) Improvement in the Sum of Individual Core Long COVID Symptom Severity as Evaluated by a Standard 4-level Likert Scale. Week 4 · Participants with at least 50% improvement in burdensome symptoms total score	2 Participants	6 Participants	1 Participants
Proportion of Subjects Achieving >=50% (>=25% and >=75% Presented Separately) Improvement in the Sum of Individual Core Long COVID Symptom Severity as Evaluated by a Standard 4-level Likert Scale. Week 4 · Participants not reaching 50% improvement in burdensome symptoms total score	88 Participants	83 Participants	89 Participants
Proportion of Subjects Achieving >=50% (>=25% and >=75% Presented Separately) Improvement in the Sum of Individual Core Long COVID Symptom Severity as Evaluated by a Standard 4-level Likert Scale. Week 8 · Participants with at least 50% improvement in burdensome symptoms total score	4 Participants	9 Participants	3 Participants
Proportion of Subjects Achieving >=50% (>=25% and >=75% Presented Separately) Improvement in the Sum of Individual Core Long COVID Symptom Severity as Evaluated by a Standard 4-level Likert Scale. Week 8 · Participants not reaching 50% improvement in burdensome symptoms total score	84 Participants	74 Participants	87 Participants
Proportion of Subjects Achieving >=50% (>=25% and >=75% Presented Separately) Improvement in the Sum of Individual Core Long COVID Symptom Severity as Evaluated by a Standard 4-level Likert Scale. Week 12 · Participants with at least 50% improvement in burdensome symptoms total score	10 Participants	7 Participants	3 Participants
Proportion of Subjects Achieving >=50% (>=25% and >=75% Presented Separately) Improvement in the Sum of Individual Core Long COVID Symptom Severity as Evaluated by a Standard 4-level Likert Scale. Week 12 · Participants not reaching 50% improvement in burdensome symptoms total score	78 Participants	78 Participants	86 Participants

SECONDARY outcome

Timeframe: Weeks 4, 8 and 12

Population: ITT population

The Core (most common) Long COVID symptoms are: fatigue, trouble sleeping, shortness of breath, general pain and discomfort, cognitive problems (most commonly known as brain fog or memory fog) and mental health symptoms. Each symptom is rated as: 0=No symptom, 1=Mild symptom (no interference with daily activities), 2=Moderate symptom (interfere and may limit daily activities), and 3=Severe symptom (strong interference preventing daily activities. The higher the rating is, worse is the symptom. 0 and 1 are deemed not burdensome, 2 and 3 are burdensome. A sum of the burdensome category is calculated for each visit and is the endpoint being evaluated for improvement since burdensome symptoms are those with highest impact on daily usual activity level.

Outcome measures

Outcome measures
Measure	Placebo for 3 Cycles (Arm 3, PPP) n=90 Participants Three cycles of 14 days of once-a-day intake of placebo, each followed by a treatment intake pause of 14 days	LAU-7b for 3 Cycles (Arm 1, AAA) n=91 Participants Three cycles of 14 days of once-a-day intake of LAU-7b, each followed by a treatment intake pause of 14 days.	LAU-7b for 1 Cycle, Then Placebo (Arm 2, APP) n=91 Participants One cycle of 14 days of once-a-day intake of LAU-7b followed by two cycles of 14 days of placebo administered similarly, each followed by a treatment intake pause of 14 days.
Proportion of Subjects Achieving >=75% (>=25% and >=50% Presented Separately) Improvement in the Sum of Individual Core Long COVID Symptom Severity as Evaluated by a Standard 4-level Likert Scale. Week 4 · Participants with at least 75% improvement in burdensome symptoms total score	0 Participants	2 Participants	0 Participants
Proportion of Subjects Achieving >=75% (>=25% and >=50% Presented Separately) Improvement in the Sum of Individual Core Long COVID Symptom Severity as Evaluated by a Standard 4-level Likert Scale. Week 4 · Participants not reaching 75% improvement in burdensome symptoms total score	90 Participants	87 Participants	90 Participants
Proportion of Subjects Achieving >=75% (>=25% and >=50% Presented Separately) Improvement in the Sum of Individual Core Long COVID Symptom Severity as Evaluated by a Standard 4-level Likert Scale. Week 8 · Participants with at least 75% improvement in burdensome symptoms total score	1 Participants	1 Participants	0 Participants
Proportion of Subjects Achieving >=75% (>=25% and >=50% Presented Separately) Improvement in the Sum of Individual Core Long COVID Symptom Severity as Evaluated by a Standard 4-level Likert Scale. Week 8 · Participants not reaching 75% improvement in burdensome symptoms total score	87 Participants	82 Participants	90 Participants
Proportion of Subjects Achieving >=75% (>=25% and >=50% Presented Separately) Improvement in the Sum of Individual Core Long COVID Symptom Severity as Evaluated by a Standard 4-level Likert Scale. Week 12 · Participants not reaching 75% improvement in burdensome symptoms total score	87 Participants	84 Participants	89 Participants
Proportion of Subjects Achieving >=75% (>=25% and >=50% Presented Separately) Improvement in the Sum of Individual Core Long COVID Symptom Severity as Evaluated by a Standard 4-level Likert Scale. Week 12 · Participants with at least 75% improvement in burdensome symptoms total score	1 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Weeks 0, 4, 8 and 12

Population: ITT population

EQ-5D-5L is a self-report survey that measures quality of life across 5 domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is scored on a 5-level severity ranking that ranges from no problems (Level 1); slight; moderate; severe; and extreme problems (Level 5). Higher values indicate worse outcomes, while lower indicate better outcomes. The subscales are combined to compute a total score index, adjusted for a standard value of general population in a country/region and averaged to produce the mean and SD. The Summary index value range is from 0 to 1, where 1 is considered the best possible health and 0 is the worst possible health. For the change in score, a positive number indicates that the scores improved from baseline.

Outcome measures

Outcome measures
Measure	Placebo for 3 Cycles (Arm 3, PPP) n=90 Participants Three cycles of 14 days of once-a-day intake of placebo, each followed by a treatment intake pause of 14 days	LAU-7b for 3 Cycles (Arm 1, AAA) n=91 Participants Three cycles of 14 days of once-a-day intake of LAU-7b, each followed by a treatment intake pause of 14 days.	LAU-7b for 1 Cycle, Then Placebo (Arm 2, APP) n=91 Participants One cycle of 14 days of once-a-day intake of LAU-7b followed by two cycles of 14 days of placebo administered similarly, each followed by a treatment intake pause of 14 days.
Change From Baseline in the EuroQol-5 Dimensions -5 Levels (EQ-5D-5L) Score Baseline Summary Index	0.58 score on a scale Standard Deviation 0.213	0.60 score on a scale Standard Deviation 0.195	0.56 score on a scale Standard Deviation 0.209
Change From Baseline in the EuroQol-5 Dimensions -5 Levels (EQ-5D-5L) Score Change from baseline at Week 4	0.04 score on a scale Standard Deviation 0.150	0.01 score on a scale Standard Deviation 0.178	0.03 score on a scale Standard Deviation 0.164
Change From Baseline in the EuroQol-5 Dimensions -5 Levels (EQ-5D-5L) Score Change from baseline at Week 12	0.08 score on a scale Standard Deviation 0.187	0.04 score on a scale Standard Deviation 0.150	0.03 score on a scale Standard Deviation 0.168
Change From Baseline in the EuroQol-5 Dimensions -5 Levels (EQ-5D-5L) Score Change from baseline at Week 8	0.03 score on a scale Standard Deviation 0.174	0.03 score on a scale Standard Deviation 0.158	0.02 score on a scale Standard Deviation 0.188

SECONDARY outcome

Timeframe: From Week 0 to Week 12

Population: ITT population

The core Long COVID symptoms are: fatigue, trouble sleeping, shortness of breath, general pain and discomfort, cognitive problems (most commonly known as brain fog or memory fog) and mental health symptoms. Each symptom is rated as: 0=No symptom, 1=Mild symptom (no interference with daily activities), 2=Moderate symptom (interfere and may limit daily activities), and 3=Severe symptom (strong interference preventing daily activities. The higher the rating is, worse is the symptom. 0 and 1 are deemed not burdensome, 2 and 3 are burdensome. Relief means a reduction of severity from moderate to none, or severe to mild/none (≥2-point Likert score change)

Outcome measures

Outcome measures
Measure	Placebo for 3 Cycles (Arm 3, PPP) n=90 Participants Three cycles of 14 days of once-a-day intake of placebo, each followed by a treatment intake pause of 14 days	LAU-7b for 3 Cycles (Arm 1, AAA) n=91 Participants Three cycles of 14 days of once-a-day intake of LAU-7b, each followed by a treatment intake pause of 14 days.	LAU-7b for 1 Cycle, Then Placebo (Arm 2, APP) n=91 Participants One cycle of 14 days of once-a-day intake of LAU-7b followed by two cycles of 14 days of placebo administered similarly, each followed by a treatment intake pause of 14 days.
Proportion of Subjects With Relief of at Least One Core Burdensome Long COVID Symptom for a Minimum of 2 Weeks. Participants with relief of at least one core burdensome symptom	9 Participants	8 Participants	9 Participants
Proportion of Subjects With Relief of at Least One Core Burdensome Long COVID Symptom for a Minimum of 2 Weeks. Participants without relief of core burdensome symptoms	81 Participants	83 Participants	82 Participants

SECONDARY outcome

Timeframe: From Week 0 to Week 12

Population: ITT population, Incidence rate of relief of at least one core burdensome symptom is less than 10%. Kaplan-Meier analysis and estimates, as well as log-rank test are not reliable and were not performed.

The core Long COVID symptoms are: fatigue, trouble sleeping, shortness of breath, general pain and discomfort, cognitive problems (brain fog or memory fog) and mental health symptoms. Each symptom is rated as: 0=No symptom, 1=Mild symptom (no interference with daily activities), 2=Moderate symptom (interfere and may limit daily activities), and 3=Severe symptom (strong interference preventing daily activities. The higher the rating is, worse is the symptom. 0 and 1 are deemed not burdensome, 2 and 3 are burdensome. This will be assessed through periodic inventory of the core Long COVID symptoms, performed at each visit. Relief means a reduction of severity from moderate to none, or severe to mild/none (≥2-point Likert score change). A longer time is worse than a short time to resolution.

Outcome measures

Outcome measures
Measure	Placebo for 3 Cycles (Arm 3, PPP) n=90 Participants Three cycles of 14 days of once-a-day intake of placebo, each followed by a treatment intake pause of 14 days	LAU-7b for 3 Cycles (Arm 1, AAA) n=91 Participants Three cycles of 14 days of once-a-day intake of LAU-7b, each followed by a treatment intake pause of 14 days.	LAU-7b for 1 Cycle, Then Placebo (Arm 2, APP) n=91 Participants One cycle of 14 days of once-a-day intake of LAU-7b followed by two cycles of 14 days of placebo administered similarly, each followed by a treatment intake pause of 14 days.
Time to Relief of the First Core Burdensome Long COVID Symptom for a Minimum of 2 Weeks, Among Those Symptoms Present at Baseline.	71.67 days Standard Deviation 14.64	60.13 days Standard Deviation 19.23	64.78 days Standard Deviation 19.38

SECONDARY outcome

Timeframe: Weeks 4, 8 and 12

Population: ITT population

The core Long COVID symptoms are: fatigue, trouble sleeping, shortness of breath, general pain and discomfort, cognitive problems (most commonly known as brain fog or memory fog) and mental health symptoms. Each symptom is rated as: 0=No symptom, 1=Mild symptom (no interference with daily activities), 2=Moderate symptom (interfere and may limit daily activities), and 3=Severe symptom (strong interference preventing daily activities. The higher the rating is, worse is the symptom. 0 and 1 are deemed not burdensome, 2 and 3 are burdensome. This will be assessed through periodic inventory of the core Long COVID symptoms, performed at each visit. Relief means a reduction of severity from moderate to none, or severe to mild/none (≥2-point Likert score change). A higher proportion is better than a lower proportion.

Outcome measures

Outcome measures
Measure	Placebo for 3 Cycles (Arm 3, PPP) n=90 Participants Three cycles of 14 days of once-a-day intake of placebo, each followed by a treatment intake pause of 14 days	LAU-7b for 3 Cycles (Arm 1, AAA) n=91 Participants Three cycles of 14 days of once-a-day intake of LAU-7b, each followed by a treatment intake pause of 14 days.	LAU-7b for 1 Cycle, Then Placebo (Arm 2, APP) n=91 Participants One cycle of 14 days of once-a-day intake of LAU-7b followed by two cycles of 14 days of placebo administered similarly, each followed by a treatment intake pause of 14 days.
Proportion of Subjects With a Sustained Clinical Recovery, Meaning a Relief of All Core Long COVID Symptoms. Week 4 · Participants achieving sustained recovery of all core symptoms	0 Participants	0 Participants	0 Participants
Proportion of Subjects With a Sustained Clinical Recovery, Meaning a Relief of All Core Long COVID Symptoms. Week 4 · Participants NOT achieving sustained recovery of all core symptoms	90 Participants	89 Participants	91 Participants
Proportion of Subjects With a Sustained Clinical Recovery, Meaning a Relief of All Core Long COVID Symptoms. Week 8 · Participants achieving sustained recovery of all core symptoms	0 Participants	0 Participants	0 Participants
Proportion of Subjects With a Sustained Clinical Recovery, Meaning a Relief of All Core Long COVID Symptoms. Week 8 · Participants NOT achieving sustained recovery of all core symptoms	90 Participants	88 Participants	90 Participants
Proportion of Subjects With a Sustained Clinical Recovery, Meaning a Relief of All Core Long COVID Symptoms. Week 12 · Participants achieving sustained recovery of all core symptoms	0 Participants	0 Participants	0 Participants
Proportion of Subjects With a Sustained Clinical Recovery, Meaning a Relief of All Core Long COVID Symptoms. Week 12 · Participants NOT achieving sustained recovery of all core symptoms	90 Participants	88 Participants	90 Participants

SECONDARY outcome

Timeframe: Weeks 0, 4, 8 and 12, as well as the longer term visit at Week 24

Population: ITT population

This will be assessed through periodic inventory of all the Long COVID symptoms, performed at each visit, relative to the baseline inventory. A lower total number is better than a higher total number.

Outcome measures

Outcome measures
Measure	Placebo for 3 Cycles (Arm 3, PPP) n=90 Participants Three cycles of 14 days of once-a-day intake of placebo, each followed by a treatment intake pause of 14 days	LAU-7b for 3 Cycles (Arm 1, AAA) n=91 Participants Three cycles of 14 days of once-a-day intake of LAU-7b, each followed by a treatment intake pause of 14 days.	LAU-7b for 1 Cycle, Then Placebo (Arm 2, APP) n=91 Participants One cycle of 14 days of once-a-day intake of LAU-7b followed by two cycles of 14 days of placebo administered similarly, each followed by a treatment intake pause of 14 days.
Change From Baseline in the Total Number of Long COVID Symptoms (Core and Non-core). Count of all Long COVID symptoms at Week 24	14.7 count of symptoms Standard Deviation 7.65	14.4 count of symptoms Standard Deviation 7.26	14.8 count of symptoms Standard Deviation 8.20
Change From Baseline in the Total Number of Long COVID Symptoms (Core and Non-core). Baseline count of all Long COVID symptoms	15.0 count of symptoms Standard Deviation 7.88	14.3 count of symptoms Standard Deviation 7.07	15.2 count of symptoms Standard Deviation 7.98
Change From Baseline in the Total Number of Long COVID Symptoms (Core and Non-core). Count of all Long COVID symptoms at Week 4	15.0 count of symptoms Standard Deviation 7.90	14.2 count of symptoms Standard Deviation 7.06	15.1 count of symptoms Standard Deviation 8.04
Change From Baseline in the Total Number of Long COVID Symptoms (Core and Non-core). Count of all Long COVID symptoms at Week 8	14.9 count of symptoms Standard Deviation 7.57	14.4 count of symptoms Standard Deviation 7.25	15.0 count of symptoms Standard Deviation 8.07
Change From Baseline in the Total Number of Long COVID Symptoms (Core and Non-core). Count of all Long COVID symptoms at Week 12	14.9 count of symptoms Standard Deviation 7.55	14.4 count of symptoms Standard Deviation 7.18	15.0 count of symptoms Standard Deviation 8.05

SECONDARY outcome

Timeframe: From Week 0 to Week 12

Population: ITT population

This will be assessed by probing the subjects at each visit. Long COVID-related unplanned medical visits includes visits to practitioner's office, urgent care visits, emergency room \<24h, or hospitalization \>24 hours. A higher proportion is worse than a lower proportion

Outcome measures

Outcome measures
Measure	Placebo for 3 Cycles (Arm 3, PPP) n=90 Participants Three cycles of 14 days of once-a-day intake of placebo, each followed by a treatment intake pause of 14 days	LAU-7b for 3 Cycles (Arm 1, AAA) n=91 Participants Three cycles of 14 days of once-a-day intake of LAU-7b, each followed by a treatment intake pause of 14 days.	LAU-7b for 1 Cycle, Then Placebo (Arm 2, APP) n=91 Participants One cycle of 14 days of once-a-day intake of LAU-7b followed by two cycles of 14 days of placebo administered similarly, each followed by a treatment intake pause of 14 days.
Proportion of Subjects With Long COVID-related Unplanned Medical Visits Participants with Long COVID-related unplanned medical visits	5 Participants	2 Participants	3 Participants
Proportion of Subjects With Long COVID-related Unplanned Medical Visits Participants without Long COVID-related unplanned medical visits	85 Participants	89 Participants	88 Participants

SECONDARY outcome

Timeframe: From Week 0 to Week 12

Population: ITT population

This will be assessed by probing the subjects at each visit, including caretakers or relatives if the subjects cannot be reached at a given visit. A higher proportion is worse than a lower proportion

Outcome measures

Outcome measures
Measure	Placebo for 3 Cycles (Arm 3, PPP) n=90 Participants Three cycles of 14 days of once-a-day intake of placebo, each followed by a treatment intake pause of 14 days	LAU-7b for 3 Cycles (Arm 1, AAA) n=91 Participants Three cycles of 14 days of once-a-day intake of LAU-7b, each followed by a treatment intake pause of 14 days.	LAU-7b for 1 Cycle, Then Placebo (Arm 2, APP) n=91 Participants One cycle of 14 days of once-a-day intake of LAU-7b followed by two cycles of 14 days of placebo administered similarly, each followed by a treatment intake pause of 14 days.
Proportion of Subjects Deceased From Any Cause Through Week 12. Participants deceased from any cause through Week 12	0 Participants	0 Participants	0 Participants
Proportion of Subjects Deceased From Any Cause Through Week 12. Participants alive through Week 12	90 Participants	91 Participants	91 Participants

SECONDARY outcome

Timeframe: From Week 0 to Week 12 and including up to the long-term follow-up at Week 24

Population: ITT population

A significant cardiovascular event is one that results in at least an acute care visit, a hospitalization or an event-related death. A higher proportion is worse than a lower proportion

Outcome measures

Outcome measures
Measure	Placebo for 3 Cycles (Arm 3, PPP) n=90 Participants Three cycles of 14 days of once-a-day intake of placebo, each followed by a treatment intake pause of 14 days	LAU-7b for 3 Cycles (Arm 1, AAA) n=91 Participants Three cycles of 14 days of once-a-day intake of LAU-7b, each followed by a treatment intake pause of 14 days.	LAU-7b for 1 Cycle, Then Placebo (Arm 2, APP) n=91 Participants One cycle of 14 days of once-a-day intake of LAU-7b followed by two cycles of 14 days of placebo administered similarly, each followed by a treatment intake pause of 14 days.
Proportion of Subjects With Significant Cardiovascular Events Participants with significant cardiovascular event through Week 24	0 Participants	0 Participants	0 Participants
Proportion of Subjects With Significant Cardiovascular Events Participants without significant cardiovascular event through Week 24	90 Participants	91 Participants	91 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 24

Population: ITT population

This is now presented as part of Outcome #17. Initially planned to be separate from the reporting and analysis of the Week 12 outcomes, a longer term contact was made at Week 24 to assess the following: Presence or not of Long COVID symptoms (total number of Long COVID symptoms).

Outcome measures

Outcome measures
Measure	Placebo for 3 Cycles (Arm 3, PPP) n=90 Participants Three cycles of 14 days of once-a-day intake of placebo, each followed by a treatment intake pause of 14 days	LAU-7b for 3 Cycles (Arm 1, AAA) n=87 Participants Three cycles of 14 days of once-a-day intake of LAU-7b, each followed by a treatment intake pause of 14 days.	LAU-7b for 1 Cycle, Then Placebo (Arm 2, APP) n=89 Participants One cycle of 14 days of once-a-day intake of LAU-7b followed by two cycles of 14 days of placebo administered similarly, each followed by a treatment intake pause of 14 days.
Health and Survival Follow-up (Week 24), Long COVID Symptom Count	14.7 counts of symptoms Standard Deviation 7.65	14.4 counts of symptoms Standard Deviation 7.26	14.8 counts of symptoms Standard Deviation 8.20

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 24

Population: ITT population

General health check-up: Assess significant cardiovascular events (one that results in at least an acute care visit, a hospitalization or an event-related death) and survival.