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

• ClinicalTrials.gov Identifier: NCT04417257
• Recruitment Status: Active, not recruiting
• First Posted: June 4, 2020
• Last Update Posted: May 18, 2021
• Sponsor: Laurent Pharmaceuticals Inc.
• Information provided by (Responsible Party): Laurent Pharmaceuticals Inc.

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
COVID-19 Disease	Drug: LAU-7b; Drug: Placebo oral capsule	Phase 2

Detailed Description:

RESOLUTION is a multicenter, randomized, double-blind, placebo-controlled Phase 2 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 240 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Double-blind, randomized, parallel groups and placebo-controlled trial
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Patients will be randomly assigned to take either the active drug (LAU-7b capsule) or a matching inactive placebo (inactive capsule)
• Primary Purpose: Treatment
• Official Title: RESOLUTION: A Double-blind, Randomized, Placebo-controlled, Pilot Phase II Study of the Efficacy and Safety of LAU-7b in the Treatment of Adult Hospitalized Patients With COVID-19 Disease
• Actual Study Start Date: June 29, 2020
• Estimated Primary Completion Date: July 15, 2021
• Estimated Study Completion Date: July 15, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: LAU-7b; Active drug as LAU-7b capsules	Drug: LAU-7b; 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.; Other Name: fenretinide
Placebo Comparator: Placebo; Placebo oral capsule (as inactive capsules identical to active arm)	Drug: Placebo oral capsule; 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.

Outcome Measures

Primary Outcome Measures :

1. Proportion of patients alive and free of respiratory failure (Ordinal Scale scores 1-4) [ Time Frame: On Day 29 ]

   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.

   1. Not hospitalized, no limitations on activities;
   2. Not hospitalized, limitation on activities;
   3. Hospitalized, not requiring supplemental oxygen;
   4. Hospitalized, requiring supplemental oxygen;
   5. Hospitalized, on non-invasive ventilation or high flow oxygen devices;
   6. Hospitalized, on invasive mechanical ventilation or extra-corporeal membrane oxygenation;
   7. Death.

Secondary Outcome Measures :

1. The safety of LAU-7b therapy will be assessed through the monitoring of treatment emergent adverse events, compared to placebo [ Time Frame: From baseline to Day 60 ]
   This will be assessed through monitoring and probing
2. Health status of the patient on the 7-point Ordinal Scale compared to placebo [ Time Frame: On Days 14 and 29 ]
   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.
3. Rate of all-causes death, depicted by a change from baseline in the Ordinal Scale score to category 7 [ Time Frame: On Days 29 and 60 ]
   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.
4. 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 [ Time Frame: From baseline to Day 60 ]
   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.
5. 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 [ Time Frame: From baseline to Day 60 ]
   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.
6. Rate of COVID-19 disease-related transfer to mechanical ventilation, depicted by a change from baseline in the ordinal scale score to category 6, compared to placebo [ Time Frame: From baseline to Day 60 ]
   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.
7. Mean change from baseline of the ordinal scale patient health status as a function of assessment time, compared to placebo [ Time Frame: From baseline to Day 60 ]
   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.
8. Time to an improvement of one category on the ordinal scale patient health status, compared to placebo [ Time Frame: From baseline to Day 60 ]
   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.
9. 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 [ Time Frame: From baseline to Day 60 ]
   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.
10. Time to mechanical ventilation, defined here as time to reach category 6 on the ordinal scale patient health status, compared to placebo [ Time Frame: From baseline to Day 60 ]
    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.
11. 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 [ Time Frame: From baseline to Day 60 ]
    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.
12. Duration of hospitalization (days) within the study period Days 1-29, compared to placebo [ Time Frame: From baseline to Day 60 ]
    Monitoring of the hospitalization
13. Time to attain an undetectable viral load through oropharyngeal swabs done at specified times, compared to placebo [ Time Frame: On Days 1, 5, 8, 12 and 14 ]
    This will be assessed through serial oropharyngeal swabs for SARS-CoV-2 viral detection
14. The change from baseline in the score obtained on the EQ-5D-5L quality-of-life survey [ Time Frame: On Days 1, 14, 29, 45 and 60 ]
    This will be assessed through questionnaire filling, in person or remotely

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Subjects must exhibit symptoms of COVID-19 disease at screening;
2. Subjects must be 18 years and older, of either gender;

3. Subjects must have at least one of the following factors/co-morbidities:

   1. Controlled or uncontrolled diabetes;
   2. Pre-existing cardiovascular disease, including hypertension;
   3. Pre-existing respiratory disease such as COPD, asthma, emphysema;
   4. Active smoker with a 20 pack-years of smoking;
   5. Obesity as depicted by body mass index ≥ 30;
   6. Laboratory tests indicative of a higher risk of COVID-19-related complications, such as troponin >1.5 upper limit of normal and/or CRP >1.5 upper limit of normal
   7. Patient aged 70 years and older who, based on the judgment of the Investigator, is at a higher risk of developing complications.
4. Subjects must have a documented positive test for the SARS-CoV-2 virus or be suspected to be positive and with a test result pending;
5. Subjects must be under observation by, or admitted to a controlled facility or hospital to receive standard-of-care for COVID-19 disease;
6. Subject's health status must be 3, 4 or 5 on the ordinal scale, and not previously a 6;
7. 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;
8. Subjects must have the ability to understand and give informed consent, which can be verbal with a witness, according to local requirements;
9. Subjects deemed capable of adequate compliance including attending scheduled visits for the duration of the study;
10. Subjects must be able to swallow the study drug capsules.

Exclusion Criteria:

1. Pregnancy or breastfeeding;

2. 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:

   1. Presence of inherited retinitis pigmentosa;
   2. Presence or history of liver failure;
   3. Presence or history of stage 4 severe chronic kidney disease or dialysis requirement;
   4. Febrile neutropenia;
   5. Presence of active cancer treated with systemic chemotherapy or radiotherapy.
3. 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;
4. 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;
5. Calculated creatinine clearance (CrCL, using the Cockroft-Gault equation for example) <60 ml/min.
6. Presence of total bilirubin >1.5 x ULN (in the absence of demonstrated Gilbert's syndrome), ALT and/or AST > 2.5 x ULN.

Contacts and Locations

Locations

United States, Arizona

Chandler Regional Medical Center / Mercy Gilbert Medical Center

Chandler, Arizona, United States, 85224

United States, Florida

Baptist Medical Center Beaches

Jacksonville Beach, Florida, United States, 32250

United States, Idaho

St Lukes Hospital

Boise, Idaho, United States, 83702

United States, Iowa

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States, 52242

United States, Maryland

Anne Arundel Medical Center, 2001 Medical Parkway, Belcher Pavillion

Annapolis, Maryland, United States, 21401

United States, Michigan

Wayne State University, Harper University Hospital and Detroit Receiving Hospital

Detroit, Michigan, United States, 48201

Henry Ford Health System

Detroit, Michigan, United States, 48202

United States, Texas

Houston Methodist Hospital

Houston, Texas, United States, 77030

Canada, Quebec

Centre d'études cliniques CIUSS SLJ, Hôpital Chicoutimi

Chicoutimi, Quebec, Canada, G7H 5H6

CIUSSSS de l'Est-de-l'Ile-de-Montréal, Hôpital Maisonneuve-Rosemont

Montréal, Quebec, Canada, H1T 2M4

Centre Hospitalier de l'Université de Montréal

Montréal, Quebec, Canada, H2X2P1

Jewish General Hospital

Montréal, Quebec, Canada, H3T 1E2

McGill University Health Centre

Montréal, Quebec, Canada, H4A 3J1

CISSS Des Laurentides

Saint-Jérôme, Quebec, Canada, J7Z 5T3

Sponsors and Collaborators

Laurent Pharmaceuticals Inc.

Investigators

• Principal Investigator: Ramy Saleh, MD; McGill University Health Centre/Research Institute of the McGill University Health Centre

More Information

• Responsible Party: Laurent Pharmaceuticals Inc.
• ClinicalTrials.gov Identifier: NCT04417257
• Other Study ID Numbers: LAU-20-01
• First Posted: June 4, 2020
• Last Update Posted: May 18, 2021
• Last Verified: May 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Laurent Pharmaceuticals Inc.:

Inflammation; Antiviral; Host-directed treatment; Docosahexaenoic acid; Pro-resolving

Additional relevant MeSH terms:

Fenretinide; Antineoplastic Agents; Anticarcinogenic Agents; Protective Agents; Physiological Effects of Drugs