Study of LAU-7b for the Treatment of COVID-19 Disease in Adults

Study Overview
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Brief Summary
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A randomized, double-blind, placebo-controlled Phase 2/3 Study of LAU-7b against confirmed COVID-19 Disease in hospitalized patients at a higher risk of complications.

Detailed Description
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RESOLUTION is a multicenter, randomized, double-blind, placebo-controlled Phase 2/3 study of LAU-7b for the treatment of COVID-19 Disease in patients at a higher risk than the general COVID-19 Disease population to develop complications while hospitalized. The goal of the study is to evaluate the efficacy of LAU-7b therapy + standard-of-care relative to placebo + standard-of-care in patients with COVID-19 Disease with confirmed SARS-CoV-2 infection. The purpose of the treatment with LAU-7b is to prevent the worsening of the health of hospitalized patients including aggravation such as recourse to mechanical ventilation and death. The means are the direct effects of LAU-7b on the resolution of inflammation, interference with viral proliferation and protection from excessive pro-inflammatory response.

Official Title
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RESOLUTION: A Double-blind, Randomized, Placebo-controlled, Phase II/III Study of the Efficacy and Safety of LAU-7b in the Treatment of Adult Hospitalized Patients With COVID-19 Disease

Conditions
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COVID-19 Disease

Intervention / Treatment
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* Drug: LAU-7b
* Drug: Placebo oral capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must exhibit symptoms (including at least one lower respiratory symptom such as shortness of breath or dyspnea) of COVID-19 disease at screening and/or since the start of their hospitalization (may include treated symptoms; Subjects must be 18 years and older, of either gender; Subjects must have at least one of the following factors/co-morbidities: Controlled or uncontrolled diabetes; Pre-existing cardiovascular disease, including hypertension; Pre-existing respiratory disease such as COPD, asthma, emphysema; Active or a former smoker with a 20 pack-years of smoking history; Obesity as depicted by body mass index ≥ 30; Laboratory tests indicative of a higher risk of COVID-19-related complications, such as troponin >1.5 upper limit of normal, D-dimer >3.0 upper limit of normal and/or CRP >1.5 upper limit of normal Patient aged 70 years and older who, based on the judgment of the Investigator, is at a higher risk of developing complications. Subjects must have a documented positive test for the SARS-CoV-2 virus; Subjects must be under observation by, or admitted to a controlled facility or hospital to receive standard-of-care for COVID-19 disease (care for COVID-19 disease should be for no more than 72 hours before screening, including any prior stay in another hospital); Subject's health status must be 3 or 4 on the ordinal scale, and not previously a 5 or a 6; 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 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 must be negative at the Screening Visit; Subjects must have the ability to understand and give informed consent, which can be verbal with a witness, according to local requirements; Subjects deemed capable of adequate compliance including attending scheduled visits for the duration of the study; Subjects must be able to swallow the study drug capsules. Exclusion Criteria: Pregnancy or breastfeeding; Health condition deemed to possibly interfere with the study endpoints and/or the safety of the patients. For example, the following conditions should be considered contraindicated for participation in the study, but this is not an exhaustive list. In case of doubt, the Investigator should consult with the sponsor's medical representative: Presence of inherited retinitis pigmentosa; Presence or history of liver failure (Child-Pugh B or C); Presence or history of stage 4 severe chronic kidney disease or dialysis requirement; Febrile neutropenia; Presence of end-stage cancer. 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 drug clinical trial within 30 days (or a minimum of 5 elimination half-lives) prior to screening, except ongoing participation in non-interventional studies; Calculated creatinine clearance (CrCL, using the Cockroft-Gault equation for example) <50 ml/min; Presence of total bilirubin >1.5 x ULN (in the absence of demonstrated Gilbert's syndrome), ALT and/or AST > 2.5 x ULN; Patient expected to be transferred to ICU or die in the next 24 hours.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double-blind, randomized, parallel groups and placebo-controlled trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LAU-7b<br>Active drug as LAU-7b capsules | Drug: LAU-7b<br>* LAU-7b will be administered orally once-a-day with the main meal of the day, if possible, for a total of up to 14 days.<br>* Other names: fenretinide;|
| Placebo Comparator: Placebo<br>Placebo oral capsule (as inactive capsules identical to active arm) | Drug: Placebo oral capsule<br>* Placebo will be administered orally once-a-day with the main meal of the day, if possible, for a total of up to 14 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients requiring mechanical ventilation and/or deceased (all causes) by Day 60 (Ordinal scale scores 6-7 inclusively) | This will be assessed through health status scoring using the World Health Organization 7-point Ordinal Scale, a higher score is worse than a low score. Not hospitalized, no limitations on activities; Not hospitalized, limitation on activities; Hospitalized, not requiring supplemental oxygen; Hospitalized, requiring supplemental oxygen; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, on invasive mechanical ventilation or extra-corporeal membrane oxygenation; Death. | From baseline to Day 60 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The safety of LAU-7b therapy will be assessed through the monitoring of treatment emergent adverse events, compared to placebo | This will be assessed through monitoring and probing | From baseline to Day 60 | 
| Rate of all-causes death, depicted by a change from baseline in the Ordinal Scale score to category 7 | This will be assessed through Day 60 health status scoring using the World Health Organization 7-point Ordinal Scale (shown with the primary outcome measure), a higher score is worse than a low score. | On Days 29 and 60 | 
| Rate of COVID-19 disease-related transfer to mechanical ventilation or ECMO, depicted by a change from baseline in the ordinal scale score to category 6, compared to placebo | This will be assessed through daily health status scoring using the World Health Organization 7-point Ordinal Scale (shown with the primary outcome measure), a higher score is worse than a low score. | From baseline to Day 60 | 
| Proportion of patients alive and free of respiratory failure by Day 29 (ordinal scale scores 1-4, inclusively) | This will be assessed by Day 29 health status scoring using the World Health Organization 7-point Ordinal Scale (shown with the primary outcome measure), a higher score is worse than a low score. | On Day 29 | 
| Rate of COVID-19 disease-related aggravation, depicted by a change from baseline in the ordinal scale score of at least one category, compared to placebo | This will be assessed through daily health status scoring using the World Health Organization 7-point Ordinal Scale (shown with the primary outcome measure), a higher score is worse than a low score. | From baseline to Day 60 | 
| Rate of COVID-19 disease-related transfer to intensive care unit, depicted by a change from baseline in the ordinal scale score to categories 5 or 6, compared to placebo | This will be assessed through daily health status scoring using the World Health Organization 7-point Ordinal Scale (shown with the primary outcome measure), a higher score is worse than a low score. | From baseline to Day 60 | 
| Health status of the patient on the 7-point Ordinal Scale compared to placebo | This will be assessed through health status scoring using the World Health Organization 7-point Ordinal Scale (shown with the primary outcome measure), a higher score is worse than a low score. | On Days 14 and 29 | 
| Mean change from baseline of the ordinal scale patient health status as a function of assessment time, compared to placebo | This will be assessed through daily health status scoring using the World Health Organization 7-point Ordinal Scale (shown with the primary outcome measure), a higher score is worse than a low score. | From baseline to Day 60 | 
| Time to an improvement of one category on the ordinal scale patient health status, compared to placebo | This will be assessed through daily health status scoring using the World Health Organization 7-point Ordinal Scale (shown with the primary outcome measure), a higher score is worse than a low score. | From baseline to Day 60 | 
| Time to recovery, defined here as the time to reach categories 2 or 1 on the ordinal scale patient health status (first occurrence if more than once), compared to placebo | This will be assessed through daily health status scoring using the World Health Organization 7-point Ordinal Scale (shown with the primary outcome measure), a higher score is worse than a low score. | From baseline to Day 60 | 
| Time to mechanical ventilation, defined here as time to reach category 6 on the ordinal scale patient health status, compared to placebo | This will be assessed through daily health status scoring using the World Health Organization 7-point Ordinal Scale (shown with the primary outcome measure), a higher score is worse than a low score. | From baseline to Day 60 | 
| Time to death, defined here as a time to reach category 7 on the ordinal scale patient health status, censored to Day 29 if it happens later than Day 29, compared to placebo | This will be assessed through daily health status scoring using the World Health Organization 7-point Ordinal Scale (shown with the primary outcome measure), a higher score is worse than a low score. | From baseline to Day 60 | 
| Duration of hospitalization (days) within the study period Days 1-60, compared to placebo | Monitoring of the hospitalization | From baseline to Day 60 | 
| The change from baseline in the score obtained on the EQ-5D-5L quality-of-life survey | This will be assessed through questionnaire filling, in person or remotely | On Days 1, 14, 29, 45 and 60 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Inflammation, Antiviral, Host-directed treatment, Docosahexaenoic acid, Pro-resolving