Study of LAU-7b for the Treatment of Coronavirus Disease 2019 (COVID-19) Disease in Adults

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

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.

RESOLUTION is a multicenter, randomized, double-blind, placebo-controlled Phase 2/3 study of LAU-7b for the treatment of COVID-19 Disease in participants 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 participants with COVID-19 Disease with confirmed SARS-CoV-2 infection. SARS is "severe acute respiratory syndrome". CoV is " Coronavirus".

The purpose of the treatment with LAU-7b is to prevent the worsening of the health of hospitalized participants 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.

Inclusion Criteria:

1. Participant exhibited symptoms [Extension Phase 3 study only: (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 have included treated symptoms)

2. Participant was 18 years and older, of either gender

3. Participant must have had 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 chronic obstructive pulmonary disease(COPD), asthma, emphysema
   4. Active [Extension Phase 3 study only: or a former smoker] with 20 pack-years of smoking history
   5. Obesity as depicted by BMI ≥30 kg/m2
   6. Laboratory tests indicative of a higher risk of COVID-19-related complications, such as troponin >1.5 the upper limit of normal (ULN), [Extension Phase 3 study only: D-dimer >3.0 ULN] and/or C reactive protein (CRP) >1.5 ULN
   7. Aged 70 years and older who, based on the judgment of the investigator, was at a higher risk of developing complications

4. Participant had a documented positive test for the SARS-CoV-2 virus [Pilot Phase 2 study only: or was suspected to be positive and with a test result pending]. [Extension Phase 3 study only: Co-infection with other viral respiratory infections was allowed and had to be documented in medical history]

5. Participant was under observation by, or admitted to, a controlled facility or hospital [Extension Phase 3 study only: for no more than 48 hours (72 hours from amendment 3 onwards) before screening, including any prior stay in another hospital] to receive standard of care (SoC) for COVID-19 disease

6. [Pilot Phase 2 study only: Participant's hs was 3, 4, or 5 on the WHO ordinal scale and not previously a "6"] [Extension Phase 3 study only: 3 or 4 on the World Health Organization (WHO) ordinal scale and not previously a "5 or a 6"]

7. If female, participant was either post-menopausal (one year or greater without menses), surgically sterile, or, for female subjects of child-bearing potential who were capable of conception had to be practicing a highly effective method of birth control (acceptable methods included 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 was not classified as an effective method of birth control. A pregnancy test had to be negative at the Screening Visit

8. Participant had the ability to understand and give informed consent, which could have been verbal with a witness, according to local requirements

9. Participant was deemed capable of adequate compliance including attending scheduled visits for the duration of the study

10. Participant was 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 participants. For example, the following conditions were considered contraindicated for participation in the study, but this was not an exhaustive list. In case of doubt, the investigator was to 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. [Pilot Phase 2 study: Presence of active cancer treated with systemic chemotherapy or radiotherapy][Extension Phase 3 study: 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 used in the study

4. Participation in another drug clinical trial within 30 days (or a minimum of 5 t½) prior to screening, except ongoing participation in non-interventional studies

5. Calculated creatinine clearance (CrCl), using the Cockroft-Gault equation for example [Pilot Phase 2 study: <60 mL/min] [Extension Phase 3 study: <30 mL/min)]

6. Presence of total bilirubin >1.5 x ULN (in the absence of demonstrated Gilbert's syndrome), alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >2.5 x ULN

7. [Extension Phase 3 study only: Subject expected to be transferred to ICU or die in the next 24 hours]