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

• ClinicalTrials.gov Identifier: NCT04417257
• Recruitment Status: Recruiting
• First Posted: June 4, 2020
• Last Update Posted: April 20, 2023
• Sponsor: Laurent Pharmaceuticals Inc.
• Information provided by (Responsible Party): Laurent Pharmaceuticals Inc.

Tracking Information

• First Submitted Date: May 28, 2020
• First Posted Date: June 4, 2020
• Last Update Posted Date: April 20, 2023
• Actual Study Start Date: June 29, 2020
• Estimated Primary Completion Date: June 30, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 5, 2022)

The proportion of patients requiring mechanical ventilation and/or deceased (all causes) by Day 60 (Ordinal scale scores 6-7 inclusively) [ Time Frame: From baseline to Day 60 ]

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.

Original Primary Outcome Measures (submitted: June 3, 2020)

Health status of the patient on the 7-point ordinal scale (World Health Organization) compared to placebo [ Time Frame: On Day 14 ]

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.

Current Secondary Outcome Measures (submitted: January 5, 2022)

• 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
• 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.
• 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 [ 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.
• Proportion of patients alive and free of respiratory failure by Day 29 (ordinal scale scores 1-4, inclusively) [ Time Frame: On Day 29 ]
  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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• Duration of hospitalization (days) within the study period Days 1-60, compared to placebo [ Time Frame: From baseline to Day 60 ]
  Monitoring of the hospitalization
• 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

Original Secondary Outcome Measures (submitted: June 3, 2020)

• 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 29 ]
  This will be assessed through monitoring and probing
• 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 29 ]
  This will be assessed through daily health status scoring using the 7-point ordinal scale
• 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 29 ]
  This will be assessed through daily health status scoring using the 7-point ordinal scale
• 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 29 ]
  This will be assessed through daily health status scoring using the 7-point ordinal scale
• Rate of COVID-19 disease-related death, depicted by a change from baseline in the ordinal scale score to category 7 [ Time Frame: On Days 14 and 29 ]
  This will be assessed through Days 14 and 29 health status scoring using the 7-point ordinal scale
• Health status of the patient on the 7-point ordinal scale (World Health Organization), compared to placebo [ Time Frame: On Day 29 ]
  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.
• 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 29 ]
  This will be assessed through daily health status scoring using the 7-point ordinal scale
• Time to an improvement of one category on the ordinal scale patient health status, compared to placebo [ Time Frame: From baseline to Day 29 ]
  This will be assessed through daily health status scoring using the 7-point ordinal scale
• 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 29 ]
  This will be assessed through daily health status scoring using the 7-point ordinal scale
• 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 29 ]
  This will be assessed through daily health status scoring using the 7-point ordinal scale
• Time to death, defined here as a tim 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 29 ]
  This will be assessed through daily health status scoring using the 7-point ordinal scale
• Duration of hospitalization (days) within the study period Days 1-29, compared to placebo [ Time Frame: From baseline to Day 29 ]
  Monitoring of the hospitalization
• 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
• The change from baseline in the score obtained on the EQ-5D-5L quality-of-life survey [ Time Frame: On Days 1, 14, 29 and 60 ]
  This will be assessed through questionnaire filling, in person or remotely

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of LAU-7b for the Treatment of COVID-19 Disease in Adults
• Official Title: 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
• Brief Summary: 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

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.

• Study Type: Interventional
• Study Phase: Phase 2; Phase 3

Study Design

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

• Condition: COVID-19 Disease

Intervention

• 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
• 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.

Study Arms

• Experimental: LAU-7b
  Active drug as LAU-7b capsules
  Intervention: Drug: LAU-7b
• Placebo Comparator: Placebo
  Placebo oral capsule (as inactive capsules identical to active arm)
  Intervention: Drug: Placebo oral capsule

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 5, 2022): 508
• Original Estimated Enrollment (submitted: June 3, 2020): 300
• Estimated Study Completion Date: June 30, 2023
• Estimated Primary Completion Date: June 30, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. 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;
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 or a former smoker with a 20 pack-years of smoking history;
   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, D-dimer >3.0 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;
5. 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);
6. Subject's health status must be 3 or 4 on the ordinal scale, and not previously a "5 or 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 (Child-Pugh B or C);
   3. Presence or history of stage 4 severe chronic kidney disease or dialysis requirement;
   4. Febrile neutropenia;
   5. Presence of end-stage cancer.
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) <50 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;
7. Patient expected to be transferred to ICU or die in the next 24 hours.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Jean-Marie Houle, PhD; 514-941-2313; jmhoule@laurentpharma.com

Contact: Radu Pislariu, MD; 514-513-2252; rpislariu@laurentpharma.com

• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT04417257
• Other Study ID Numbers: LAU-20-01
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Laurent Pharmaceuticals Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Laurent Pharmaceuticals Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Jean-Marie Houle, PhD; Laurent Pharmaceuticals Inc.

• PRS Account: Laurent Pharmaceuticals Inc.
• Verification Date: April 2023