Evaluate the Efficacy and Safety of FB2001 in Hospitalized Patients With Moderate to Severe COVID-19 (BRIGHT Study)

Study Overview
=================
Brief Summary
-----------------
This study is a double-blind, randomized, placebo-controlled study to evaluate the efficacy and safety of FB2001 in hospitalized patients with moderate to severe Coronavirus Disease 2019 (COVID-19). A total of about 1188 subjects are planned to be enrolled. The subjects will be randomized in a 1:1 ratio to FB2001 group or placebo group while both receiving standard of care treatment.

Detailed Description
-----------------
Coronavirus Disease 2019 (COVID-19) is a respiratory illness that can spread from person to person. The infectious agent that causes COVID 19 is a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified during a recent outbreak in December 2019. Patients with COVID-19 have symptoms of fever, cough, and shortness of breath along with non-specific symptoms including myalgia and fatigue. FB2001 is a small-molecule inhibitor of coronavirus 3CL protease (3CLpro). In two phase I clinical trials, we completed doses of FB2001 that were safe, and were projected to be effective in patients according to its pharmacokinetic profile. This study is a double-blind, randomized, placebo-controlled study to evaluate the efficacy and safety of FB2001 in hospitalized patients with moderate to severe Coronavirus Disease 2019 (COVID 19). A total of about 1188 subjects are planned to be enrolled. The subjects will be randomized in a 1:1 ratio to FB2001 group or placebo group while both receiving standard of care treatment.

Official Title
-----------------
A Phase II/III, Double-Blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of FB2001 in Hospitalized Patients With Moderate to Severe COVID-19

Conditions
-----------------
COVID-19

Intervention / Treatment
-----------------
* Drug: FB2001
* Drug: FB2001 placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: ≥18 years old, male or female. Subjects hospitalized with moderate to severe COVID-19 with a category 4 or 5 on an 8-category ordinal scale. Has laboratory-confirmed COVID-19 infection within 5 days prior to randomization. Initial COVID-19 symptom onset within 5 days prior to randomization and ≥1 sign/symptom attributable to COVID-19 within 24 hours before randomization. The underlying medical condition was well controlled prior to SARS CoV 2 infection and does not affect daily life. Subject who did not receive COVID 19 (primary series or booster) vaccine within the 6 months prior to screening. The subject is willing to provide written informed consent to participate in the study after reading the informed consent form and the information provided and has had the opportunity to discuss the study with the Investigator or designee. The subject is able to communicate satisfactorily with the Investigator and to participate in, and comply with, the requirements of the study. The subject is able to understand the nature of the study and any potential hazards associated with participating in it. Negative pregnancy test for female subjects of childbearing potential and female subjects less than 2 years of postmenopause. Women of childbearing potential (WOCBP) and Women of non-childbearing potential are eligible to participate. Both women of childbearing potential and women of non-childbearing potential must use an approved method of birth control and agrees to continue to use this method for the duration of the study and for 30 days after taking the last dose of FB2001. Exclusion Criteria: Pregnant or breastfeeding, or intending to become pregnant during the study or within 30 days after the final dose or who are not willing to use a highly effective method of contraception. HIV-infected subjects with viral load greater than 400 copies/mL or CD4 count less than 200 cell/µL from known medical history within past 6 months of the Screening Visit. Subject with moderate to severe hepatic impairment or acute liver failure. Known severe kidney disease. Participated in other intervention studies within 6 months. Has any condition for which, in the opinion of the Investigator, participation would not be in the best interest of the participant or that could prevent, limit, or confound the protocol-specified assessments including but not limited to participants who are not expected to survive longer than 48 hours after randomization, or participants who are expected to require mechanical ventilation within 48 hours after randomization, or participants with a recent history of mechanical ventilation. Subjects receiving any medications or substances that are strong inhibitors or inducers of CYP3A within 14 days of randomization. Received, ongoing or planed treatment with other anti-SARS CoV 2 therapeutics (including but not limited to known anti-SARS CoV 2 antibodies, small molecule antivirals, etc., other than remdesivir). Other conditions that may increase the risk of study participation or, in the Investigator's judgment, make the participant inappropriate for the study. Have known hypersensitivity to FB2001 or its excipients. Any planned vaccine within 28 days following the last administration of FB2001 for Injection.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FB2001 group<br>FB2001 will be administered by IV infusion twice daily (BID) for up to 5 days, plus SOC. | Drug: FB2001<br>* FB2001 for injection will be reconstituted with 100 mL of normal saline prior to intravenous infusion. FB2001 will be administered by IV infusion over approximately 60 minutes.<br>* Other names: DC402234;|
| Placebo Comparator: Placebo group<br>Placebo will be administered by IV infusion twice daily (BID) for up to 5 days, plus SOC. | Drug: FB2001 placebo<br>* Placebo will be reconstituted with 100 mL of normal saline prior to intravenous infusion. Placebo will be administered by IV infusion over approximately 60 minutes.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to sustained recovery (in days) from randomization up to Day 29. | Day of sustained recovery is defined as the first day on which a subject is discharged from hospital, or hospitalized for infection-control or other non-medical reasons through Day 29 | Up to Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with mechanical ventilation or all-cause-death | Proportion of participants with mechanical ventilation or all-cause-death in FB2001 group and placebo group | Through Day 29 and Day 60 | 
| Proportion of participants with sustained recovery on Day 6 | no specific description | On Day 6 | 
| Clinical status category as assessed by an 8-category ordinal scale daily while hospitalized and on Days, 15 and 29. | no specific description | On Days 15 and 29 | 
| Duration of each targeted COVID-19 sign/symptom until discharge | Duration of each targeted COVID-19 sign/symptom until discharge | Up to Day 29 | 
| Severity of each targeted COVID-19 sign/symptom until discharge | no specific description | Up to Day 29 | 
| Days of supplemental oxygen (if applicable) | no specific description | Up to Day 29 | 
| Duration of non-invasive ventilation/high-flow oxygen (if applicable) | no specific description | Up to Day 29 | 
| Days of invasive mechanical ventilation/ECMO (if applicable) | no specific description | Up to Day 29 | 
| Time to achieve SARS-CoV-2 virologic clearance | no specific description | Up to Day 29 | 
| Proportion of participants achieving SARS-CoV-2 virologic clearance on Day 3, 5, 8, 15 and 29 | no specific description | On Day 3, 5, 8, 15 and 29 | 
| Viral load change (log10) from baseline on Day 3, 5, 8 and 15. | no specific description | On Day 3, 5, 8 and 15 | 
| Population pharmacokinetic (PK) parameters to be measured/analyzed, including AUC, Cmax and Ctrough | no specific descriptionsa | Day0-Day 5 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)