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

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

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.

Study Overview

• Status: Recruiting
• Conditions: COVID-19
• Intervention / Treatment: Drug: FB2001; Drug: FB2001 placebo

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.

• Study Type: Interventional
• Enrollment (Anticipated): 1188
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Chengchen Sun; Phone Number: +86 02569760330; Email: ccsun@frontierbiotech.com
• Study Contact Backup: Name: Cheng Yao; Email: yaocheng@frontierbiotech.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Beijing Ditan Hospital Capital Medical University
    • Contact: Cuiyun Wu
    • Principal Investigator: Ronghua Jin
  • Shanghai
    • Shanghai, Shanghai, China
      • Recruiting
      • Huashan Hospital Fudan University
      • Contact: Yunao Zhou
      • Principal Investigator: Wenhong Zhang

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. ≥18 years old, male or female.
2. Subjects hospitalized with moderate to severe COVID-19 with a category 4 or 5 on an 8-category ordinal scale.
3. Has laboratory-confirmed COVID-19 infection within 5 days prior to randomization.
4. Initial COVID-19 symptom onset within 5 days prior to randomization and ≥1 sign/symptom attributable to COVID-19 within 24 hours before randomization.
5. The underlying medical condition was well controlled prior to SARS CoV 2 infection and does not affect daily life.
6. Subject who did not receive COVID 19 (primary series or booster) vaccine within the 6 months prior to screening.
7. 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.
8. The subject is able to communicate satisfactorily with the Investigator and to participate in, and comply with, the requirements of the study.
9. The subject is able to understand the nature of the study and any potential hazards associated with participating in it.
10. 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:

1. 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.
2. 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.
3. Subject with moderate to severe hepatic impairment or acute liver failure.
4. Known severe kidney disease.
5. Participated in other intervention studies within 6 months.
6. 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.
7. Subjects receiving any medications or substances that are strong inhibitors or inducers of CYP3A within 14 days of randomization.
8. 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).
9. Other conditions that may increase the risk of study participation or, in the Investigator's judgment, make the participant inappropriate for the study.
10. Have known hypersensitivity to FB2001 or its excipients.
11. Any planned vaccine within 28 days following the last administration of FB2001 for Injection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FB2001 group; FB2001 will be administered by IV infusion twice daily (BID) for up to 5 days, plus SOC.	Drug: FB2001; 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.; Other Names: DC402234
Placebo Comparator: Placebo group; Placebo will be administered by IV infusion twice daily (BID) for up to 5 days, plus SOC.	Drug: FB2001 placebo; 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.

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
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
Proportion of participants with sustained recovery on Day 6	no specific description	On Day 6

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of Treatment-Emergent Adverse Events (TEAEs)	safety evaluation	Up to Day 60
Incidence of withdrawals due to Adverse Events (AEs)	safety evaluation	Up to Day 60
Change in vital signs including blood pressure, heart rate, respiratory rate, and temperature from baseline	safety evaluation	Up to Day 29
Incidence of Treatment-Related Adverse Events (TRAEs)	safety evaluation	Up to Day 60
Incidence of Serious Adverse Events (SAEs)	safety evaluation	Up to Day 60
Change/shifts in laboratory values from baseline	safety evaluation	Up to Day 29
Change in abnormal Electrocardiogram (ECG) parameters from baseline	safety evaluation	Up to Day 29
Changes in abnormal physical examination findings from baseline	safety evaluation	Up to Day 29
Change in oxygen saturation (SpO2) from baseline	safety evaluation	Up to Day 29

Collaborators and Investigators

• Sponsor: Frontier Biotechnologies Inc.
• Investigators: Study Director: Cheng Yao, Frontier Biotechnologies Inc.

Publications and helpful links

General Publications

• Shang W, Dai W, Yao C, Xu L, Tao X, Su H, Li J, Xie X, Xu Y, Hu M, Xie D, Jiang H, Zhang L, Liu H. In vitro and in vivo evaluation of the main protease inhibitor FB2001 against SARS-CoV-2. Antiviral Res. 2022 Dec;208:105450. doi: 10.1016/j.antiviral.2022.105450. Epub 2022 Oct 29.

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2022
• Primary Completion (Anticipated): November 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: June 27, 2022
• First Submitted That Met QC Criteria: July 4, 2022
• First Posted (Actual): July 6, 2022

Study Record Updates

• Last Update Posted (Actual): January 5, 2023
• Last Update Submitted That Met QC Criteria: January 3, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: FB2001-301

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No