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ESSOR is a double-blind, placebo-controlled study of the orally-administered antiviral and inflammation-controlling LAU-7b for the treatment of adults with Long COVID and moderate to severe symptoms.
ESSOR is a multicenter, randomized, double-blind, placebo-controlled Phase 2/3 study of LAU-7b for the treatment of Long COVID in non-hospitalized adults with moderate to severe Long COVID symptoms.
The goal of the study is to evaluate the efficacy of LAU-7b therapy + stable symptomatic standard-of-care relative to placebo + stable symptomatic standard-of-care at reducing the overall Long COVID burden by improving multiple dimensions of quality-of-life and alleviating the symptoms.
This study is a logical extension of investigating LAU-7b as a potential therapeutic against various phases of COVID-19.
LAU-7b is therefore being proposed as a potential disease-modifying medication for the treatment of Long COVID.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LAU-7b for 3 cycles | Experimental | Each study arm will consist of three (3) cycles of 14 days of treatment intake each spaced by a treatment holiday of 14 days. |
|
| LAU-7b for 1 cycle, then placebo | Experimental | Each study arm will consist of three (3) cycles of 14 days of treatment intake each spaced by a treatment holiday of 14 days. |
|
| Placebo for 3 cycles | Placebo Comparator | Each study arm will consist of three (3) cycles of 14 days of treatment intake each spaced by a treatment holiday of 14 days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LAU-7b for 3 cycles | Drug | Three cycles of 14 days of once-a-day intake of LAU-7b, each followed by a treatment intake pause of 14 days. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Physical Component Summary (PCS) of the Medical Outcomes Study Short-Form-36 (SF-36) at Week 12 | 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. | Week 0 and 12 |
| Measure | Description | Time Frame |
|---|---|---|
| Safety of LAU-7b, Overview | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Health and Survival Follow-up (Week 24), Long COVID Symptom Count | 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). | Week 24 |
Inclusion Criteria:
Exclusion Criteria:
Subject is currently hospitalized (any reason);
Pregnancy or breastfeeding;
Any COVID vaccination within 4 weeks of screening or planned during study participation;
Presence of any health condition judged by the investigator to be directly causing one or more of the most common Long COVID symptoms;
Health condition deemed to possibly interfere with the study endpoints and/or the safety of the subjects. For example, the following conditions should be considered contraindicated for participation in the study. In case of doubt, the Investigator should consult with the Sponsor's medical representative:
Presence or suspicion of drug or alcohol abuse, as judged by the Investigator;
Known history of a severe allergy or sensitivity to retinoids, or with known allergies to excipients in the oral capsule formulation proposed to be used in the study;
Participation in another interventional drug, alimentary supplement, psychological or device...etc. clinical trial within 30 days (or a minimum of 5 elimination half-lives for drugs) prior to screening, except ongoing participation in non-interventional studies;
Presence of total bilirubin >1.5 x Upper Limit of Normal (in the absence of demonstrated Gilbert's syndrome), alanine aminotransferase and/or aspartate aminotransferase > 2.5 x Upper Limit of Normal (unless there are clinical evidences of hepatic steatosis).
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| Name | Affiliation | Role |
|---|---|---|
| Jean-Marie Houle, PhD | Laurent Pharmaceuticals Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CIUSS du Saguenay-Lac-St-Jean - Hôpital Chicoutimi | Chicoutimi | Quebec | G7H 5H6 | Canada | ||
| Institut de Recherches Cliniques de Montréal |
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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
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| FG002 | 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 |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | LAU-7b for 1 Cycle, Then Placebo (Arm 2, APP) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in Physical Component Summary (PCS) of the Medical Outcomes Study Short-Form-36 (SF-36) at Week 12 | 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. | Intent-to-Treat (ITT) population | Posted | Mean | Standard Deviation | score on a scale | Week 0 and 12 |
|
Adverse events were collected from the time of informed consent until the Week 12 in person follow-up, or until early termination or death, whichever occurred first. Treatment emergent adverse events (TEAE) occurred from the first dose of study treatment (or worsened after first dose of study treatment) until the end of the AE collection period. Exceptions were LONG COVID symptoms (Endpoint #17) and significant cardiovascular events (Endpoints #20 & 22), both monitored until Week 24.
To avoid duplicating data between the AE log and the LONG COVID symptom log, all the LONG COVID symptoms (core and non-core) were only entered in the LONG COVID symptom log even if they appeared or worsened after the baseline inventory. However, if a LONG COVID symptom appeared or worsened after the baseline inventory and is unexpected and/or exceeded in severity the normal LONG COVID evolution, then the said symptom were to be entered on the AE log during the AE collection period.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Femur fracture | Injury, poisoning and procedural complications | MedDRA 26.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dry eye | Eye disorders | MedDRA 26.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Vice President Clinical Development | Laurent Pharmaceuticals Inc. | 514-941-2313 | jmhoule@laurentpharma.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Feb 13, 2024 | Sep 9, 2025 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 28, 2024 | Sep 9, 2025 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D000094024 | Post-Acute COVID-19 Syndrome |
| D000086382 | COVID-19 |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
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| ID | Term |
|---|---|
| D017313 | Fenretinide |
| D000073893 | Sugars |
| ID | Term |
|---|---|
| D012176 | Retinoids |
| D002338 | Carotenoids |
| D011090 | Polyenes |
| D000475 | Alkenes |
| D006839 |
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Parallel, regimen-finding, adaptive design well-controlled randomized clinical trial
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Identically appearing active and placebo capsules
| LAU-7b for 1 cycle, then placebo | Drug | 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 | Other | Three cycles of 14 days of once-a-day intake of placebo, each followed by a treatment intake pause of 14 days |
|
|
| From Week 0 to Week 12 |
| Patient Global Impression of Change (PGI-C) | 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. | Weeks 4, 8 and 12 |
| Proportion of Participants With Marked Improvement in PGI-C | 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. | Weeks 4, 8 and 12 |
| Change From Baseline in the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Scale | 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. | Weeks 0, 4, 8 and 12 |
| Change From Baseline in the DePaul Post-Exertional Malaise Questionnaire (DPEMQ) | 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. | Weeks 0 and 12 |
| Change From Baseline in Physical Component Summary (PCS) of the Medical Outcomes Study Short-Form-36 (SF-36) at Weeks 4 and 8 | 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. | Weeks 0, 4 and 8 |
| Change From Baseline in the Other Aspects (Domain Scales) Than the PCS of the Medical Outcomes Study Short-Form-36 (SF-36) | 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. | Weeks 0, 4, 8 and 12 |
| Proportion of Subjects Who Judge to Have Regained Their Daily Usual Activity Level of Pre-causative-infection. | 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." | From Week 0 through Weeks 4, 8 and 12 |
| 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. | 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. | Weeks 4, 8 and 12 |
| 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. | 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. | Weeks 4, 8 and 12 |
| 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. | 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. | Weeks 4, 8 and 12 |
| Change From Baseline in the EuroQol-5 Dimensions -5 Levels (EQ-5D-5L) Score | 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. | Weeks 0, 4, 8 and 12 |
| Proportion of Subjects With Relief of at Least One Core Burdensome Long COVID Symptom for a Minimum of 2 Weeks. | 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) | From Week 0 to Week 12 |
| Time to Relief of the First Core Burdensome Long COVID Symptom for a Minimum of 2 Weeks, Among Those Symptoms Present at Baseline. | 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. | From Week 0 to Week 12 |
| Proportion of Subjects With a Sustained Clinical Recovery, Meaning a Relief of All Core Long COVID Symptoms. | 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. | Weeks 4, 8 and 12 |
| Change From Baseline in the Total Number of Long COVID Symptoms (Core and Non-core). | 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. | Weeks 0, 4, 8 and 12, as well as the longer term visit at Week 24 |
| Proportion of Subjects With Long COVID-related Unplanned Medical Visits | 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 | From Week 0 to Week 12 |
| Proportion of Subjects Deceased From Any Cause Through Week 12. | 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 | From Week 0 to Week 12 |
| Proportion of Subjects With Significant Cardiovascular Events | 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 | From Week 0 to Week 12 and including up to the long-term follow-up at Week 24 |
| Health and Survival Follow-up (Week 24), Significant Cardiovascular Events | 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. | Week 24 |
| Baseline Values of Systemic Biomarkers of Hematologic Function (Except Hemoglobin & Hematocrit) | These will be assessed by blood samples taken at randomization visit in a subgroup of participants consented to contribute samples. | Week 0 |
| Baseline Values of Systemic Biomarkers of Hematologic Function (Hemoglobin) | These will be assessed by blood samples taken at randomization visit in a subgroup of participants consented to contribute samples. | Week 0 |
| Baseline Values of Systemic Biomarkers of Hematologic Function (Hematocrit) | These will be assessed by blood samples taken at randomization visit in a subgroup of participants consented to contribute samples. | Week 0 |
| Changes Relative to Baseline (Percent Change) of Systemic Biomarkers of Hematologic Function | These will be assessed by blood samples taken at specific visits of the study in a subgroup of participants consented to contribute samples. | Weeks 0, 2 and 10 |
| Baseline Values of Systemic Biomarkers of Inflammation and Immunologic Function (Parameters in pg/mL) | These will be assessed by blood samples taken at randomization visits of the study in a subgroup of participants consented to contribute samples. | Week 0 |
| Baseline Values of Systemic Biomarkers of Inflammation and Immunologic Function (Calprotectin, C-reactive Protein) | These will be assessed by blood samples taken at randomization visits of the study in a subgroup of participants consented to contribute samples. | Week 0 |
| Baseline Values of Systemic Biomarkers of Inflammation and Immunologic Function (Serotonin, Tryptophan and Taurine) | These will be assessed by blood samples taken at randomization visits of the study in a subgroup of participants consented to contribute samples. | Week 0 |
| Changes Relative to Baseline (Percent Change) of Systemic Biomarkers of Inflammation and Immunologic Function | These will be assessed by blood samples taken at specific visits of the study in a subgroup of participants consented to contribute samples. | Weeks 0, 2 and 10 |
| Biomarkers of Pharmacodynamic Activity - Plasma Retinol | These will be assessed by blood samples taken at specific visits of the study in a subgroup of participants consented to contribute samples. | Weeks 0, 2 and 10 |
| Biomarkers of Pharmacodynamic Activity - Systematic Inflammation Index (SII) | These will be assessed by blood samples taken at specific visits of the study in a subgroup of participants consented to contribute samples. SII = (N × P)/L, where N, P and L (cells*10^9/L) represent absolute neutrophil counts, platelet counts and lymphocyte counts. Since SII is a ratio of concentrations, it is unitless. | Weeks 0, 2 and 10 |
| Changes Relative to Baseline (Percent Change) of Biomarker of Pharmacodynamic Activity - Retinol | These will be assessed by blood samples taken at specific visits of the study in a subgroup of participants consented to contribute samples. | Weeks 0, 2 and 10 |
| Montreal |
| Quebec |
| H2W 1R7 |
| Canada |
| Montreal General Hospital | Montreal | Quebec | H3G 1A4 | Canada |
| Diex Recherche Québec Inc. | Québec | Quebec | G1V 4T3 | Canada |
| Centre Hospitalier de l'Université de Sherbrooke | Sherbrooke | Quebec | J1H 5N4 | Canada |
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.
| BG002 | 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 |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Age, Customized | Count of Participants | Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Body Weight | Mean | Standard Deviation | kilograms |
|
| Body Mass Index (BMI) | Mean | Standard Deviation | kilograms/square meter |
|
| Vaccinated against Coronavirus Disease 2019 (COVID-19) | Count of Participants | Participants |
|
| OG000 |
| 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. |
| OG001 | 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. |
| OG002 | 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 |
|
|
|
| Secondary | Safety of LAU-7b, Overview | 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. | Safety population includes all participants who received at least one dose of study treatment. | Posted | Number | participants | From Week 0 to Week 12 |
|
|
|
| Secondary | Patient Global Impression of Change (PGI-C) | 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. | ITT population | Posted | Count of Participants | Participants | Weeks 4, 8 and 12 |
|
|
|
| Secondary | Proportion of Participants With Marked Improvement in PGI-C | 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. | ITT population | Posted | Count of Participants | Participants | Weeks 4, 8 and 12 |
|
|
|
|
| Secondary | Change From Baseline in the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Scale | 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. | ITT population | Posted | Mean | Standard Deviation | units on a scale | Weeks 0, 4, 8 and 12 |
|
|
|
|
| Secondary | Change From Baseline in the DePaul Post-Exertional Malaise Questionnaire (DPEMQ) | 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. | ITT population | Posted | Count of Participants | Participants | Weeks 0 and 12 |
|
|
|
|
| Secondary | Change From Baseline in Physical Component Summary (PCS) of the Medical Outcomes Study Short-Form-36 (SF-36) at Weeks 4 and 8 | 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. | ITT population | Posted | Mean | Standard Deviation | units on a scale | Weeks 0, 4 and 8 |
|
|
|
|
| Secondary | Change From Baseline in the Other Aspects (Domain Scales) Than the PCS of the Medical Outcomes Study Short-Form-36 (SF-36) | 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. | ITT population | Posted | Mean | Standard Deviation | units on a scale | Weeks 0, 4, 8 and 12 |
|
|
|
|
| Secondary | Proportion of Subjects Who Judge to Have Regained Their Daily Usual Activity Level of Pre-causative-infection. | 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." | ITT population | Posted | Count of Participants | Participants | From Week 0 through Weeks 4, 8 and 12 |
|
|
|
|
| Secondary | 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. | 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. | ITT population | Posted | Count of Participants | Participants | Weeks 4, 8 and 12 |
|
|
|
|
| Secondary | 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. | 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. | ITT population | Posted | Count of Participants | Participants | Weeks 4, 8 and 12 |
|
|
|
|
| Secondary | 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. | 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. | ITT population | Posted | Count of Participants | Participants | Weeks 4, 8 and 12 |
|
|
|
|
| Secondary | Change From Baseline in the EuroQol-5 Dimensions -5 Levels (EQ-5D-5L) Score | 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. | ITT population | Posted | Mean | Standard Deviation | score on a scale | Weeks 0, 4, 8 and 12 |
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|
|
| Secondary | Proportion of Subjects With Relief of at Least One Core Burdensome Long COVID Symptom for a Minimum of 2 Weeks. | 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) | ITT population | Posted | Count of Participants | Participants | From Week 0 to Week 12 |
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|
|
|
| Secondary | Time to Relief of the First Core Burdensome Long COVID Symptom for a Minimum of 2 Weeks, Among Those Symptoms Present at Baseline. | 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. | 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. | Posted | Mean | Standard Deviation | days | From Week 0 to Week 12 |
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|
|
| Secondary | Proportion of Subjects With a Sustained Clinical Recovery, Meaning a Relief of All Core Long COVID Symptoms. | 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. | ITT population | Posted | Count of Participants | Participants | Weeks 4, 8 and 12 |
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|
|
| Secondary | Change From Baseline in the Total Number of Long COVID Symptoms (Core and Non-core). | 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. | ITT population | Posted | Mean | Standard Deviation | count of symptoms | Weeks 0, 4, 8 and 12, as well as the longer term visit at Week 24 |
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|
| Secondary | Proportion of Subjects With Long COVID-related Unplanned Medical Visits | 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 | ITT population | Posted | Count of Participants | Participants | From Week 0 to Week 12 |
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|
|
| Secondary | Proportion of Subjects Deceased From Any Cause Through Week 12. | 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 | ITT population | Posted | Count of Participants | Participants | From Week 0 to Week 12 |
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|
|
| Secondary | Proportion of Subjects With Significant Cardiovascular Events | 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 | ITT population | Posted | Count of Participants | Participants | From Week 0 to Week 12 and including up to the long-term follow-up at Week 24 |
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| Other Pre-specified | Health and Survival Follow-up (Week 24), Long COVID Symptom Count | 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). | ITT population | Posted | Mean | Standard Deviation | counts of symptoms | Week 24 |
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| Other Pre-specified | Health and Survival Follow-up (Week 24), Significant Cardiovascular Events | 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. | ITT population | Posted | Count of Participants | Participants | Week 24 |
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|
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| Other Pre-specified | Baseline Values of Systemic Biomarkers of Hematologic Function (Except Hemoglobin & Hematocrit) | These will be assessed by blood samples taken at randomization visit in a subgroup of participants consented to contribute samples. | Biomarker subset of participants | Posted | Mean | Standard Deviation | cells*10^9/L | Week 0 |
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|
|
| Other Pre-specified | Baseline Values of Systemic Biomarkers of Hematologic Function (Hemoglobin) | These will be assessed by blood samples taken at randomization visit in a subgroup of participants consented to contribute samples. | Biomarker subset of participants | Posted | Mean | Standard Deviation | g/L | Week 0 |
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|
|
| Other Pre-specified | Baseline Values of Systemic Biomarkers of Hematologic Function (Hematocrit) | These will be assessed by blood samples taken at randomization visit in a subgroup of participants consented to contribute samples. | Biomarker subset of participants | Posted | Mean | Standard Deviation | L/L | Week 0 |
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|
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| Other Pre-specified | Changes Relative to Baseline (Percent Change) of Systemic Biomarkers of Hematologic Function | These will be assessed by blood samples taken at specific visits of the study in a subgroup of participants consented to contribute samples. | Biomarker subset of participants | Posted | Mean | Standard Deviation | Percentage of change | Weeks 0, 2 and 10 |
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|
|
| Other Pre-specified | Baseline Values of Systemic Biomarkers of Inflammation and Immunologic Function (Parameters in pg/mL) | These will be assessed by blood samples taken at randomization visits of the study in a subgroup of participants consented to contribute samples. | Biomarker subset of participants | Posted | Mean | Standard Deviation | pg/mL | Week 0 |
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| Other Pre-specified | Baseline Values of Systemic Biomarkers of Inflammation and Immunologic Function (Calprotectin, C-reactive Protein) | These will be assessed by blood samples taken at randomization visits of the study in a subgroup of participants consented to contribute samples. | Biomarker subset of participants | Posted | Mean | Standard Deviation | µg/mL | Week 0 |
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|
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| Other Pre-specified | Baseline Values of Systemic Biomarkers of Inflammation and Immunologic Function (Serotonin, Tryptophan and Taurine) | These will be assessed by blood samples taken at randomization visits of the study in a subgroup of participants consented to contribute samples. | Biomarker subset of participants | Posted | Mean | Standard Deviation | µmol/L | Week 0 |
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|
|
| Other Pre-specified | Changes Relative to Baseline (Percent Change) of Systemic Biomarkers of Inflammation and Immunologic Function | These will be assessed by blood samples taken at specific visits of the study in a subgroup of participants consented to contribute samples. | Biomarker subset of participants | Posted | Mean | Standard Deviation | Percentage of change | Weeks 0, 2 and 10 |
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|
|
| Other Pre-specified | Biomarkers of Pharmacodynamic Activity - Plasma Retinol | These will be assessed by blood samples taken at specific visits of the study in a subgroup of participants consented to contribute samples. | Biomarker subset of participants | Posted | Mean | Standard Deviation | µmol/L | Weeks 0, 2 and 10 |
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|
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| Other Pre-specified | Biomarkers of Pharmacodynamic Activity - Systematic Inflammation Index (SII) | These will be assessed by blood samples taken at specific visits of the study in a subgroup of participants consented to contribute samples. SII = (N × P)/L, where N, P and L (cells*10^9/L) represent absolute neutrophil counts, platelet counts and lymphocyte counts. Since SII is a ratio of concentrations, it is unitless. | Biomarker subset of participants | Posted | Mean | Standard Deviation | unitless value | Weeks 0, 2 and 10 |
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|
|
| Other Pre-specified | Changes Relative to Baseline (Percent Change) of Biomarker of Pharmacodynamic Activity - Retinol | These will be assessed by blood samples taken at specific visits of the study in a subgroup of participants consented to contribute samples. | Biomarker subset of participants | Posted | Mean | Standard Deviation | percentage of baseline | Weeks 0, 2 and 10 |
|
|
|
| 0 |
| 90 |
| 1 |
| 90 |
| 71 |
| 90 |
| EG001 | 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. | 0 | 91 | 2 | 91 | 71 | 91 |
| EG002 | 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 | 0 | 90 | 2 | 90 | 59 | 90 |
| Suicidal ideation | Psychiatric disorders | MedDRA 26.1 | Systematic Assessment |
|
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA 26.1 | Systematic Assessment |
|
| Cholecystitis | Hepatobiliary disorders | MedDRA 26.1 | Systematic Assessment |
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| Cholecystectomy | Surgical and medical procedures | MedDRA 26.1 | Systematic Assessment |
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| Vision blurred | Eye disorders | MedDRA 26.1 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 26.1 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 26.1 | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | MedDRA 26.1 | Systematic Assessment |
|
| Gastroesophageal reflux disease | Gastrointestinal disorders | MedDRA 26.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 26.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 26.1 | Systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA 26.1 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 26.1 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 26.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 26.1 | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 26.1 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 26.1 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 26.1 | Systematic Assessment |
|
Not provided
Not provided
| D014777 |
| Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D000094025 | Post-Infectious Disorders |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Hydrocarbons, Acyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D053138 | Cyclohexenes |
| D003510 | Cyclohexanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D013729 | Terpenes |
| D010860 | Pigments, Biological |
| D001685 | Biological Factors |
| D002241 | Carbohydrates |
|
| Participants with treatment-emergent adverse events leading to treatment discontinuation |
|
| Participants with treatment-emergent adverse events with fatal outcome |
|
| Participants with suspected unexpected serious adverse reaction (SUSAR) |
|
| Much improved |
|
| Minimally improved |
|
| No change |
|
| Minimally worse |
|
| Much worse |
|
| Very much worse |
|
| PGI-C at Week 8 |
|
|
| PGI-C at Week 12 |
|
|
| No marked improvement |
|
| Marked improvement of PGI-C at Week 8 |
|
|
| Marked improvement of PGI-C at Week 12 |
|
|
| Fisher Exact |
| 1.000 |
| Superiority |
| Week 4 comparison, null hypothesis of no difference | Fisher Exact | 0.1027 | Superiority |
| Week 8 comparison, null hypothesis of no difference | Fisher Exact | 0.0229 | Superiority |
| Week 8 comparison, null hypothesis of no difference | Fisher Exact | 1.000 | Superiority |
| Week 8 comparison, null hypothesis of no difference | Fisher Exact | 0.0296 | Superiority |
| Week 12 comparison, null hypothesis of no difference | Fisher Exact | 0.8448 | Superiority |
| Week 12 comparison, null hypothesis of no difference | Fisher Exact | 0.0307 | Superiority |
| Week 12 comparison, null hypothesis of no difference | Fisher Exact | 0.0105 | Superiority |
|
| Change from baseline at Week 4 |
|
| Value at Week 8 |
|
| Change from baseline at Week 8 |
|
| Value at Week 12 |
|
| Change from baseline at Week 12 |
|
Week 4 comparison, null hypothesis of no difference |
| Mixed Models Analysis |
| 0.6834 |
No adjustment for multiple comparisons, alpha set at 0.05 |
| Least Square Means difference |
| -0.5 |
| Standard Error of the Mean |
| 1.30 |
| 2-Sided |
| Superiority |
| Week 4 comparison, null hypothesis of no difference | Mixed Models Analysis | 0.1061 | No adjustment for multiple comparisons, alpha set at 0.05 | Least Square Means difference | 2.1 | Standard Error of the Mean | 1.31 | 2-Sided | Superiority |
| Week 8 comparison, null hypothesis of no difference | Mixed Models Analysis | 0.0854 | No adjustment for multiple comparisons, alpha set at 0.05 | Least Square Means difference | 2.2 | Standard Error of the Mean | 1.30 | 2-Sided | Superiority |
| Week 8 comparison, null hypothesis of no difference | Mixed Models Analysis | 0.6686 | No adjustment for multiple comparisons, alpha set at 0.05 | Least Square Means difference | -0.6 | Standard Error of the Mean | 1.30 | 2-Sided | Superiority |
| Week 8 comparison, null hypothesis of no difference | Mixed Models Analysis | 0.0331 | No adjustment for multiple comparisons, alpha set at 0.05 | Least Square Means difference | 2.8 | Standard Error of the Mean | 1.31 | 2-Sided | Superiority |
| Week 12 comparison, null hypothesis of no difference | Mixed Models Analysis | 0.4327 | No adjustment for multiple comparisons, alpha set at 0.05 | Least Square Means difference | -1.0 | Standard Error of the Mean | 1.29 | 2-Sided | Superiority |
| Week 12 comparison, null hypothesis of no difference | Mixed Models Analysis | 0.1247 | No adjustment for multiple comparisons, alpha set at 0.05 | Least Square Means difference | -2.0 | Standard Error of the Mean | 1.29 | 2-Sided | Superiority |
| Week 12 comparison, null hypothesis of no difference | Mixed Models Analysis | 0.4606 | No adjustment for multiple comparisons, alpha set at 0.05 | Least Square Means difference | 1.0 | Standard Error of the Mean | 1.31 | 2-Sided | Superiority |
| Participants without PEM |
|
| Week 12 |
|
|
| Fisher Exact |
| 0.4965 |
Alpha set at 0.05 |
| Superiority |
| Baseline comparison, null hypothesis of no difference | Fisher Exact | 0.2093 | Alpha set at 0.05 | Superiority |
| Week 12 comparison, null hypothesis of no difference | Fisher Exact | 1.000 | Alpha set at 0.05 | Superiority |
| Week 12 comparison, null hypothesis of no difference | Fisher Exact | 1.000 | Alpha set at 0.05 | Superiority |
| Week 12 comparison, null hypothesis of no difference | Fisher Exact | 1.000 | Alpha set at 0.05 | Superiority |
| Change from baseline PCS at Week 4 |
|
|
| PCS at Week 8 |
|
|
| Change from baseline PCS at Week 8 |
|
|
Week 4 comparison, null hypothesis of no difference |
| Mixed Models Analysis |
| 0.1150 |
No adjustment for multiple comparisons, alpha set at 0.05 |
| Least Square Means difference |
| 1.8 |
| Standard Error of the Mean |
| 1.11 |
| 2-Sided |
| Superiority |
| Week 4 comparison, null hypothesis of no difference | Mixed Models Analysis | 0.2296 | No adjustment for multiple comparisons, alpha set at 0.05 | Least Square Means difference | -1.3 | Standard Error of the Mean | 1.11 | 2-Sided | Superiority |
| Week 8 comparison, null hypothesis of no difference | Mixed Models Analysis | 0.7761 | No adjustment for multiple comparisons, alpha set at 0.05 | Least Square Means difference | 0.3 | Standard Error of the Mean | 1.11 | 2-Sided | Superiority |
| Week 8 comparison, null hypothesis of no difference | Mixed Models Analysis | 0.8544 | No adjustment for multiple comparisons, alpha set at 0.05 | Least Square Means difference | 0.2 | Standard Error of the Mean | 1.11 | 2-Sided | Superiority |
| Week 8 comparison, null hypothesis of no difference | Mixed Models Analysis | 0.9197 | No adjustment for multiple comparisons, alpha set at 0.05 | Least Square Means difference | 0.1 | Standard Error of the Mean | 1.11 | 2-Sided | Superiority |
|
| Change from baseline vitality score at Week 8 |
|
| Change from baseline vitality score at Week 12 |
|
| Baseline physical functioning score |
|
| Change from baseline physical functioning score at Week 4 |
|
| Change from baseline physical functioning score at Week 8 |
|
| Change from baseline physical functioning score at Week 12 |
|
| Baseline bodily pain score |
|
| Change from baseline bodily pain score at Week 4 |
|
| Change from baseline bodily pain score at Week 8 |
|
| Change from baseline bodily pain score at Week 12 |
|
| Baseline general health perception score |
|
| Change from baseline general health perception score at Week 4 |
|
| Change from baseline general health perception score at Week 8 |
|
| Change from baseline general health perception score at Week 12 |
|
| Baseline physical role functioning score |
|
| Change from baseline physical role functioning score at Week 4 |
|
| Change from baseline physical role functioning score at Week 8 |
|
| Change from baseline physical role functioning score at Week 12 |
|
| Baseline emotional role functioning |
|
| Change from baseline emotional role functioning score at Week 4 |
|
| Change from baseline emotional role functioning score at Week 8 |
|
| Change from baseline emotional role functioning score at Week 12 |
|
| Baseline social role functioning score |
|
| Change from baseline social role functioning score at Week 4 |
|
| Change from baseline social role functioning score at Week 8 |
|
| Change from baseline social role functioning score at Week 12 |
|
| Baseline mental health score |
|
| Change from baseline mental health score at Week 4 |
|
| Change from baseline mental health score at Week 8 |
|
| Change from baseline mental health score at Week 12 |
|
Vitality domain, Week 12 comparison, null hypothesis of no difference
| Mixed Models Analysis |
| 0.4427 |
Alpha set at 0.05 |
| Leat Square Means difference |
| -1.9 |
| Standard Error of the Mean |
| 2.50 |
| 2-Sided |
| Superiority |
| Vitality domain, Week 12 comparison, null hypothesis of no difference | Mixed Models Analysis | 0.7783 | Alpha set at 0.05 | Least Square Means difference | 0.7 | Standard Error of the Mean | 2.52 | 2-Sided | Superiority |
| Physical Functioning domain, Week 12 comparison, null hypothesis of no difference | Mixed Models Analysis | 0.7488 | Alpha set at 0.05 | Least Square Means difference | -1.0 | Standard Error of the Mean | 3.19 | 2-Sided | Superiority |
| Physical Functioning domain, Week 12 comparison, null hypothesis of no difference | Mixed Models Analysis | 0.5557 | Least Square Means difference | 1.9 | Standard Error of the Mean | 3.18 | 2-Sided | Superiority |
| Physical Functioning domain, Week 12 comparison, null hypothesis of no difference | Mixed Models Analysis | 0.3679 | Alpha set at 0.05 | Least Square Means difference | -2.9 | Standard Error of the Mean | 3.22 | 2-Sided | Superiority |
| Bodily Pain domain, Week 12 comparison, null hypothesis of no difference | Mixed Models Analysis | 0.0044 | Alpha set at 0.05 | Least Squre Means difference | -8.0 | Standard Error of the Mean | 2.78 | 2-Sided | Superiority |
| Bodily Pain domain, Week 12 comparison, null hypothesis of no difference | Mixed Models Analysis | 0.0158 | Alpha set at 0.05 | Least Square Means difference | -6.8 | Standard Error of the Mean | 2.79 | 2-Sided | Superiority |
| Bodily Pain domain, Week 12 comparison, null hypothesis of no difference | Mixed Models Analysis | 0.6682 | Alpha set at 0.05 | Least Square Means difference | -1.2 | Standard Error of the Mean | 2.81 | 2-Sided | Superiority |
| General Health domain, Week 12 comparison, null hypothesis of no difference | Mixed Models Analysis | 0.2448 | Alpha set at 0.05 | Least Square Means difference | 2.2 | Standard Error of the Mean | 1.90 | 2-Sided | Superiority |
| General Health domain, Week 12 comparison, null hypothesis of no difference | Mixed Models Analysis | 0.4702 | Alpha set at 0.05 | Least Square Means difference | 1.4 | Standard Error of the Mean | 1.90 | 2-Sided | Superiority |
| General Health domain, Week 12 comparison, null hypothesis of no difference | Mixed Models Analysis | 0.6627 | Alpha set at 0.05 | Least Square Means difference | 0.8 | Standard Error of the Mean | 1.92 | 2-Sided | Superiority |
| Role Physical Functioning domain, Week 12 comparison, null hypothesis of no difference | Mixed Models Analysis | 0.2774 | Alpha set at 0.05 | Least Square Means difference | -3.1 | Standard Error of the Mean | 2.85 | 2-Sided | Superiority |
| Role Physical Functioning domain, Week 12 comparison, null hypothesis of no difference | Mixed Models Analysis | 0.1537 | Least Square Means difference | -4.1 | Standard Error of the Mean | 2.85 | 2-Sided | Superiority |
| Role Physical Functioning domain, Week 12 comparison, null hypothesis of no difference | Mixed Models Analysis | 0.7355 | Alpha set at 0.05 | Least Square Means difference | 1.0 | Standard Error of the Mean | 2.87 | 2-Sided | Superiority |
| Role Emotional Functioning domain, Week 12 comparison, null hypothesis of no difference | Mixed Models Analysis | 0.1757 | Alpha set at 0.05 | Least Square Means difference | -8.0 | Standard Error of the Mean | 5.90 | 2-Sided | Superiority |
| Rome Emotional Functioning domain, Week 12 comparison, null hypothesis of no difference | Mixed Models Analysis | 0.0649 | Alpha set at 0.05 | Least Square Means difference | -10.9 | Standard Error of the Mean | 5.89 | 2-Sided | Superiority |
| Role Emotional Functioning domain, Week 12 comparison, null hypothesis of no difference | Mixed Models Analysis | 0.6262 | Alpha set at 0.05 | Least Square Means difference | 2.9 | Standard Error of the Mean | 5.93 | 2-Sided | Superiority |
| Social Role Functioning domain, Week 12 comparison, null hypothesis of no difference | Mixed Models Analysis | 0.9709 | Alpha set at 0.05 | Least Square Means difference | 0.1 | Standard Error of the Mean | 2.92 | 2-Sided | Superiority |
| Social Role Functioning domain, Week 12 comparison, null hypothesis of no difference | Mixed Models Analysis | 0.3201 | Alpha set at 0.05 | Least Square Means difference | -2.9 | Standard Error of the Mean | 2.92 | 2-Sided | Superiority |
| Social Role Functioning domain, Week 12 comparison, null hypothesis of no difference | Mixed Models Analysis | 0.3065 | Alpha set at 0.05 | Least Square Means difference | 3.0 | Standard Error of the Mean | 2.95 | 2-Sided | Superiority |
| Mental Health domain, Week 12 comparison, null hypothesis of no difference | Mixed Models Analysis | 0.2891 | Alpha set at 0.05 | Least Square Means difference | 1.0 | Standard Error of the Mean | 0.95 | 2-Sided | Superiority |
| Mental Health domain, Week 12 comparison, null hypothesis of no difference | Mixed Models Analysis | 0.8714 | Alpha set at 0.05 | Least Square Means difference | -0.2 | Standard Error of the Mean | 0.95 | 2-Sided | Superiority |
| Mental Health domain, Week 12 comparison, null hypothesis of no difference | Mixed Models Analysis | 0.2260 | Alpha set at 0.05 | Least Square Means difference | 1.2 | Standard Error of the Mean | 0.96 | 2-Sided | Superiority |
| Participants who judge NOT to have regained daily usual activity level |
|
| Week 8 |
|
|
| Week 12 |
|
|
| Fisher Exact |
| 0.2459 |
Alpha set at 0.05 |
| Superiority |
| Week 4 comparison, null hypothesis of no difference | Fisher Exact | 0.2459 | Alpha set at 0.05 | Superiority |
| Week 8 comparison, null hypothesis of no difference | Fisher Exact | 1.000 | Alpha set at 0.05 | Superiority |
| Week 8 comparison, null hypothesis of no difference | Fisher Exact | 1.000 | Superiority |
| Week 8 comparison, null hypothesis of no difference | Superiority | No comparison possible since zero count in both groups |
| Week 12 comparison, null hypothesis of no difference | Fisher Exact | 0.4972 | Alpha set to 0.05 | Superiority |
| Week 12 comparison, null hypothesis of no difference | Fisher Exact | 1.000 | Alpha set at 0.05 | Superiority |
| Week 12 comparison, null hypothesis of no difference | Fisher Exact | 1.000 | Superiority |
| Participants not reaching 25% improvement in burdensome symptoms total score |
|
| Week 8 |
|
|
| Week 12 |
|
|
| Fisher Exact |
| 1.000 |
Alpha set at 0.05 |
| Superiority |
| Week 4 comparison, null hypothesis of no difference | Fisher Exact | 0.3081 | Superiority |
| Week 8 comparison, null hypothesis of no difference | Fisher Exact | 0.066 | Alpha set at 0.05 | Superiority |
| Week 8 comparison, null hypothesis of no difference | Fisher Exact | 0.0297 | Alpha set at 0.05 | Superiority |
| Week 8 comparison, null hypothesis of no difference | Fisher Exact | 0.8471 | Alpha set at 0.05 | Superiority |
| Week 12 comparison, null hypothesis of no difference | Fisher Exact | 0.7009 | Alpha set at 0.05 | Superiority |
| Week 12 comparison, null hypothesis of no difference | Fisher Exact | 0.7064 | Alpha set at 0.05 | Superiority |
| Week 12 comparison, null hypothesis of no difference | Fisher Exact | 1.000 | Alpha set at 0.05 | Superiority |
| Participants not reaching 50% improvement in burdensome symptoms total score |
|
| Week 8 |
|
|
| Week 12 |
|
|
| 1.000 |
| Superiority |
| Week 4 comparison, null hypothesis of no difference | Fisher Exact | 0.0643 | Alpha set at 0.05 | Superiority |
| Week 8 comparison, null hypothesis of no difference | Fisher Exact | 0.1531 | Superiority |
| Week 8 comparison, null hypothesis of no difference | Fisher Exact | 0.7187 | Superiority |
| Week 8 comparison, null hypothesis of no difference | Fisher Exact | 0.0720 | Alpha set at 0.05 | Superiority |
| Week 12 comparison, null hypothesis of no difference | Fisher Exact | 0.6117 | Alpha set at 0.05 | Superiority |
| Week 12 comparison, null hypothesis of no difference | Fisher Exact | 0.0479 | Alpha set at 0.05 | Superiority |
| Week 12 comparison, null hypothesis of no difference | Fisher Exact | 0.2042 | Alpha set at 0.05 | Superiority |
| Participants not reaching 75% improvement in burdensome symptoms total score |
|
| Week 8 |
|
|
| Week 12 |
|
|
| Superiority |
Comparison not possible since zero counts in both groups |
| Week 4 comparison, null hypothesis of no difference | Fisher Exact | 0.2458 | Superiority |
| Week 8 comparison, null hypothesis of no difference | Fisher Exact | 1.000 | Alpha set at 0.05 | Superiority |
| Week 8 comparison, null hypothesis of no difference | Fisher Exact | 0.4944 | Alpha set at 0.05 | Superiority |
| Week 8 comparison, null hypothesis of no difference | Fisher Exact | 0.4798 | Superiority |
| Week 12 comparison, null hypothesis of no difference | Fisher Exact | 1.000 | Alpha set at 0.05 | Superiority |
| Week 12 comparison, null hypothesis of no difference | Fisher Exact | 0.4972 | Alpha set at 0.05 | Superiority |
| Week 12 comparison, null hypothesis of no difference | Fisher Exact | 0.4885 | Alpha set at 0.05 | Superiority |
|
| Change from baseline at Week 8 |
|
| Change from baseline at Week 12 |
|
Week 4 comparison, null hypothesis of no difference |
| Mixed Models Analysis |
| 0.7088 |
No adjustment for multiple comparisons, alpha set at 0.05 |
| Least Square Means difference |
| -0.0 |
| Standard Error of the Mean |
| 0.02 |
| 2-Sided |
| Superiority |
| Week 4 comparison, null hypothesis of no difference | Mixed Models Analysis | 0.6610 | No adjustment for multiple comparisons, alpha set at 0.05 | Least Square Means difference | -0.0 | Standard Error of the Mean | 0.02 | 2-Sided | Superiority |
| Week 8 comparison, null hypothesis of no difference | Mixed Models Analysis | 0.7580 | No adjustment for multiple comparisons, alpha set at 0.05 | Least Square Means difference | 0.0 | Standard Error of the Mean | 0.02 | 2-Sided | Superiority |
| Week 8 comparison, null hypothesis of no difference | Mixed Models Analysis | 0.4974 | No adjustment for multiple comparisons, alpha set at 0.05 | Least Square Means difference | -0.0 | Standard Error of the Mean | 0.02 | 2-Sided | Superiority |
| Week 8 comparison, null hypothesis of no difference | Mixed Models Analysis | 0.3289 | No adjustment for multiple comparisons, alpha set at 0.05 | Least Square Means difference | 0.0 | Standard Error of the Mean | 0.02 | 2-Sided | Superiority |
| Week 12 comparison, null hypothesis of no difference | Mixed Models Analysis | 0.1700 | No adjustment for multiple comparisons, alpha set at 0.05 | Least Square Means difference | -0.0 | Standard Error of the Mean | 0.02 | 2-Sided | Superiority |
| Week 12 comparison, null hypothesis of no difference | Mixed Models Analysis | 0.0557 | No adjustment for multiple comparisons, alpha set at 0.05 | Least Square Means difference | -0.0 | Standard Error of the Mean | 0.02 | 2-Sided | Superiority |
| Week 12 comparison, null hypothesis of no difference | Mixed Models Analysis | 0.6008 | No adjustment for multiple comparisons, alpha set at 0.05 | Least Square Means difference | 0.0 | Standard Error of the Mean | 0.02 | 2-Sided | Superiority |
|
| 1.000 |
Alpha set at 0.05 |
| Superiority |
| Null hypothesis of no difference | Fisher Exact | 1.000 | Alpha set at 0.05 | Superiority |
| Participants NOT achieving sustained recovery of all core symptoms |
|
| Week 8 |
|
|
| Week 12 |
|
|
| Count of all Long COVID symptoms at Week 4 |
|
|
| Count of all Long COVID symptoms at Week 8 |
|
|
| Count of all Long COVID symptoms at Week 12 |
|
|
| Count of all Long COVID symptoms at Week 24 |
|
|
| ANOVA |
| 0.9928 |
Treatment group effect, alpha set at 0.05 |
| Superiority |
| Week 12 comparison, null hypothesis of no difference | ANOVA | 0.8363 | Treatment group effect, alpha set at 0.05 | Superiority |
| Week 24 comparison, null hypothesis of no difference | ANOVA | 0.6930 | Treatment group effect, alpha set at 0.05 | Superiority |
|
| 0.4967 |
Alpha set at 0.05 |
| Superiority |
| Null hypothesis of no difference | Fisher Exact | 1.000 | Alpha set at 0.05 | Superiority |
|
|
|
| Platelet count (10^9/L) - Baseline |
|
| Neutrophil count (10^9/L) - Baseline |
|
| Erythrocyte % change from baseline at Week 10 |
|
|
| Leucocyte % change from baseline at Week 2 |
|
|
| Leucocyte % change from baseline at Week 10 |
|
|
| Platelet % change from baseline at Week 2 |
|
|
| Platelet % change from baseline at Week 10 |
|
|
| Hematocrit % change at Week 2 |
|
|
| Hematocrit % change at Week 10 |
|
|
| Hemoglobin % change at Week 2 |
|
|
| Hemoglobin % change at Week 10 |
|
|
| Neutrophil % change at Week 2 |
|
|
| Neutrophil % change at Week 10 |
|
|
|
| Baseline Interleukin-8 (pg/mL) |
|
| Baseline Interleukin-10 (pg/mL) |
|
| Baseline Interferon-lambda-1 (pg/mL) |
|
| Baseline Interferon-lambda-3 (pg/mL) |
|
| Baseline Interferon-gamma (pg/mL) |
|
| Baseline Tumor Necrosis Factor alpha (pg/mL) |
|
| Baseline Cluster of Differentiation 40 ligand (pg/mL) |
|
| Baseline Interferon gamma-induced protein 10 (pg/mL) |
|
|
|
| Baseline Taurine (µmol/L) |
|
| Interleukin-1-beta % change from baseline at Week 10 |
|
|
| Interleukin-6 % change from baseline at Week 2 |
|
|
| Interleukin-6 % change from baseline at Week 10 |
|
|
| Interleukin-8 % change from baseline at Week 2 |
|
|
| Interleukin-8 % change from baseline at Week 10 |
|
|
| Interleukin-10 % change at Week 2 |
|
|
| Interleukin-10 % change at Week 10 |
|
|
| Interferon-lambda-1 % change at Week 2 |
|
|
| Interferon-lambda-1 % change at Week 10 |
|
|
| Interferon-lambda-3 % change at Week 2 |
|
|
| Interferon-lambda-3 % change at Week 10 |
|
|
| Interferon-gamma % change at Week 2 |
|
|
| Interferon-gamma % change at Week 10 |
|
|
| Tumor Necrosis Factor alpha % change at Week 2 |
|
|
| Tumor Necrosis Factor alpha % change at Week 10 |
|
|
| Cluster of Differentiation 40 ligand % change at Week 2 |
|
|
| Cluster of Differentiation 40 ligand % change at Week 10 |
|
|
| Interferon gamma-induced protein 10 % change at Week 2 |
|
|
| Interferon gamma-induced protein 10 % change at Week 10 |
|
|
| Calprotectin % change at Week 2 |
|
|
| Calprotectin % change at Week 10 |
|
|
| C-reactive protein % change at Week 2 |
|
|
| C-reactive protein % change at Week 10 |
|
|
| Serotonin % change at Week 2 |
|
|
| Serotonin % change at Week 10 |
|
|
| Tryptophan % change at Week 2 |
|
|
| Tryptophan % change at Week 10 |
|
|
| Taurine % change at Week 2 |
|
|
| Taurine % change at Week 10 |
|
|
| Week 2 Retinol (µmol/L) |
|
|
| Week 10 Retinol (µmol/L) |
|
|
| Week 2 Systematic Inflammation Index |
|
|
| Week 10 Systematic Inflammation Index |
|
|
| Retinol % change from baseline at Week 10 |
|
|