Clinical trial NCT04417257: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: COVID-19 Disease
Keywords: Inflammation
Antiviral
Host-directed treatment
Docosahexaenoic acid
Pro-resolving
Lead sponsor: Laurent Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2020-06-04
Enrollment: 125
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blind, randomized, parallel groups and placebo-controlled trial
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: The proportion of patients requiring mechanical ventilation and/or deceased (all causes) by Day 60 (Ordinal scale scores 6-7 inclusively)
timeFrame: From baseline to Day 60
Secondary outcomes:
measure: The safety of LAU-7b therapy will be assessed through the monitoring of treatment emergent adverse events, compared to placebo
timeFrame: From baseline to Day 60
measure: Rate of all-causes death, depicted by a change from baseline in the Ordinal Scale score to category 7
timeFrame: On Days 29 and 60
measure: 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
timeFrame: From baseline to Day 60
measure: Proportion of patients alive and free of respiratory failure by Day 29 (ordinal scale scores 1-4, inclusively)
timeFrame: On Day 29
measure: 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
timeFrame: From baseline to Day 60
measure: 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
timeFrame: From baseline to Day 60
measure: Health status of the patient on the 7-point Ordinal Scale compared to placebo
timeFrame: On Days 14 and 29
measure: Mean change from baseline of the ordinal scale patient health status as a function of assessment time, compared to placebo
timeFrame: From baseline to Day 60
measure: Time to an improvement of one category on the ordinal scale patient health status, compared to placebo
timeFrame: From baseline to Day 60
measure: 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
timeFrame: From baseline to Day 60
measure: Time to mechanical ventilation, defined here as time to reach category 6 on the ordinal scale patient health status, compared to placebo
timeFrame: From baseline to Day 60
measure: 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
timeFrame: From baseline to Day 60
measure: Duration of hospitalization (days) within the study period Days 1-60, compared to placebo
timeFrame: From baseline to Day 60
measure: The change from baseline in the score obtained on the EQ-5D-5L quality-of-life survey
timeFrame: On Days 1, 14, 29, 45 and 60
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Chandler Regional Medical Center / Mercy Gilbert Medical Center
state: Arizona
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital Presbyterian
state: California
city: Sacramento
country: United States
facility: University of California Davis Medical Center
state: California
city: Danbury
country: United States
facility: Nuvance Health - Danbury Hospital
state: Connecticut
city: Washington
country: United States
facility: MedStar Washington Hospital Center
state: District of Columbia
city: Jacksonville Beach
country: United States
facility: Baptist Medical Center Beaches
state: Florida
city: Boise
country: United States
facility: St Lukes Hospital
state: Idaho
city: Chicago
country: United States
facility: NorthShore University Health System - Swedish Hospital
state: Illinois
city: Glenview
country: United States
facility: NorthShore University Health System - Glenbrook Hospital
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Annapolis
country: United States
facility: Anne Arundel Medical Center, 2001 Medical Parkway, Belcher Pavillion
state: Maryland
city: Detroit
country: United States
facility: Wayne State University, Harper University Hospital and Detroit Receiving Hospital
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Las Vegas
country: United States
facility: University Medical Center of Southern Nevada
state: Nevada
city: Staten Island
country: United States
facility: Staten Island University Hospital North
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University Health Science
state: North Carolina
city: Columbus
country: United States
facility: OhioHealth Riverside Methodist Hospital
state: Ohio
city: Kettering
country: United States
facility: Kettering Health
state: Ohio
city: Sayre
country: United States
facility: Robert Packer Hospital
state: Pennsylvania
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Mesquite
country: United States
facility: PRX Research /Dallas Regional Medical Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Health
state: Utah
city: Chicoutimi
country: Canada
facility: Centre d'études cliniques CIUSS SLJ, Hôpital Chicoutimi
state: Quebec
city: Montréal
country: Canada
facility: CIUSSSS de l'Est-de-l'Ile-de-Montréal, Hôpital Maisonneuve-Rosemont
state: Quebec
city: Montréal
country: Canada
facility: Centre Hospitalier de l'Université de Montréal
state: Quebec
city: Montréal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Montréal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Saint-Jérôme
country: Canada
facility: CISSS Des Laurentides
state: Quebec
Study officials:
affiliation: Laurent Pharmaceuticals Inc.
name: Jean-Marie Houle, PhD
role: STUDY_DIRECTOR
References: