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

Laurent Pharmaceuticals Inc.272 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

272

Conditions

Long COVID

Interventions

LAU-7b for 3 cyclesDRUG

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 placeboDRUG

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 cyclesOTHER

Three cycles of 14 days of once-a-day intake of placebo, each followed by a treatment intake pause of 14 days

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Subjects must be 18 years and older, of either gender, and able to give informed consent; 2. Subjects diagnosed with Long COVID and exhibiting persisting, relapsing or new Long COVID symptom(s) at least 12 weeks beyond the start (test positivity or symptom onset) of the causative COVID-19 infection; 3. At least one of the Long COVID symptoms must be from the core list of Long COVID symptoms, and be present for a minimum of 2 weeks prior to screening and of moderate or severe intensity as per the 4-level Likert severity scale (0 to 3; 0 = no symptoms; 1 = mild symptoms; 2 = moderate symptoms; 3 = severe symptoms); 4. If female, must be either post-menopausal (one year or greater without menses), surgically sterile, or, for female subjects of child-bearing potential who are capable of conception, must be: practicing a highly effective method of birth control (acceptable methods include intrauterine device, complete abstinence, spermicide + barrier, male partner surgical sterilization, or hormonal contraception) during the study treatment intake and through 30 days after the last dose of the study medication. Periodical abstinence is not classified as an effective method of birth control. A pregnancy test for female subjects of child-bearing potential must be negative at the Screening Visit; 5. Subjects deemed capable of adequate compliance including attending scheduled follow-up calls/visits for the duration of the study, have internet access and able to read and answer questionnaires on electronic Patient Reported Outcomes platform (ePRO) or paper; 6. Screening laboratory test and vital signs results within ranges compatible with the subject's health condition, as per investigator's judgement. See also the last exclusion for certain liver function tests; 7. Subjects deemed capable of swallowing the study treatment capsules Exclusion Criteria: 1. Subject is currently hospitalized (any reason); 2. Pregnancy or breastfeeding; 3. Any COVID vaccination within 4 weeks of screening or planned during study participation; 4. Presence of any health condition judged by the investigator to be directly causing one or more of the most common Long COVID symptoms; 5. 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: * Febrile neutropenia; * Fibromyalgia deemed to interfere with generalized pain measurements; * Presence of end-stage cancer (palliative care). 6. Presence or suspicion of drug or alcohol abuse, as judged by the Investigator; 7. 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; 8. 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; 9. 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).

Locations (5)

CIUSS du Saguenay-Lac-St-Jean - Hôpital Chicoutimi

Chicoutimi, Quebec, Canada

Institut de Recherches Cliniques de Montréal

Montreal, Quebec, Canada

Montreal General Hospital

Montreal, Quebec, Canada

Diex Recherche Québec Inc.

Québec, Quebec, Canada

Outcomes

Primary Outcomes

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.

Time frame: Week 0 and 12

Secondary Outcomes

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.

Time frame: 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.

Time frame: Weeks 4, 8 and 12

Proportion of Participants With Marked Improvement in PGI-C

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Centre Hospitalier de l'Université de Sherbrooke

Sherbrooke, Quebec, Canada

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.

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: 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.

Time frame: 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."

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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)

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: 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

Time frame: 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

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