Evaluate the Efficacy and Safety of FB2001 for Inhalation in Patients With Mild to Moderate COVID-19

Study Overview
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Brief Summary
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This study is a double-blind,randomized,placebo-controlled study to evaluate the efficacy and safety of FB2001 for Inhalation in patients with mild to moderate Coronavirus Disease 2019(COVID-19). A total of about 1336 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
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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 phase I clinical trial, FB2001 for Inhalation were safe and tolerable well in healthy subjects, 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 for Inhalation in patients with mild to moderate Coronavirus Disease 2019 (COVID-19). 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
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A Phase II/III,Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of FB2001 for Inhalation in Patients With Mild to Moderate COVID-19

Conditions
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Mild to Moderate COVID-19

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years, male or female; Confirmed SARS-CoV-2 infection as determined by Reverse Transcription - Polymerase Chain Reaction(RT -PCR) in any specimen collected within 5 days prior to randomization. Note: RT-PCR is the preferred method; however, with evolving approaches to laboratory confirmation of SARS-CoV-2 infection, other molecular or antigen tests that detect viral RNA or protein are allowed if authorized for use in the country; Patients with mild or moderate COVID-19. Initial onset of signs/symptoms attributable to COVID -19 within 3 days prior to the day of randomization and at least one of the specified signs/symptoms attributable to COVID -19 present on the day of randomization; Women of childbearing potential who have a negative serum or urine pregnancy test prior to the first study dose; Patient who is willing to cooperate and able to participate in the trial, adhered to all requirements of the protocol, and provided written informed consent. Exclusion Criteria: Patients who are currently or are expected to potentially progress to severe/critical COVID-19 within 48 h of randomization; Patients with chronic respiratory diseases, including bronchial asthma and chronic obstructive pulmonary disease etc. Known history of moderate-severe liver impairment (e.g., Child-Pugh grade B or C, alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 5x upper limit normal (ULN) , or acute liver failure within 6 months prior to screening;. Known history of severe renal impairment (e.g., Chronic Kidney Disease-Improved Prediction Equations(CKD-EPI)formula based on serum creatinine, estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m2), or was receiving renal replacement therapy, such as peritoneal dialysis or hemodialysis, within 6 months prior to screening; Impaired immune system (including patients treated with systemic corticosteroids or other immunosuppressive agents, or cancer progression or recurrence) Suspected or confirmed concurrent active systemic infections other than COVID-19 that may interfere with the assessment of response to study interventions. Need for radiotherapy, chemotherapy, emergency surgery or surgical treatment at screening, or other emergencies (e.g. acute coronary syndrome, acute pulmonary embolism, etc.). Patients with a history of cardiopulmonary resuscitation or major surgery within 30 days prior to randomization, and patients with other potentially life-threatening clinical conditions or other emergencies. History of hypersensitivity or other contraindications to any component of the study intervention. Patients who received or expected to receive anti-SARS-CoV-2 viral drugs (e.g., nirmatrelvir/ritonavir, molnupiravir, etc.) within 14 days prior to randomization. Have received (within 30 days prior to randomization or within 5 half-lives, whichever is longer) or expect to receive COVID-19 monoclonal antibody or recovery COVID-19 plasma therapy. Any SARS-CoV-2 vaccination within 3 months prior to randomization. Within 28 days or 5 half-lives (whichever is longer) prior to randomization or in clinical studies with other investigational drugs or devices, including studies for COVID-19. Mental illnesses that, in the judgment of the investigator, are not appropriate for participation in this study. Any other situation that the investigator believes may affect the subject's informed consent or adherence to the protocol, or the subject's participation in the study may affect the outcome of the study or his or her own safety, in the investigator's judgment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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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 nebulized inhalation, plus Standard Of Care(SOC) | Drug: FB2001<br>* FB2001 for Inhalation will be reconstituted with normal saline prior to nebulized inhalation. FB2001 will be administered by nebulized inhalation.<br>* Other names: FB2001 for Inhalation;|
| Placebo Comparator: Placebo group<br>Placebo will be administered by nebulized inhalation, plus Standard Of Care(SOC) | Drug: FB2001 placebo<br>* FB2001 placebo will be reconstituted with normal saline prior to nebulized inhalation. FB2001 placebo will be administered by nebulized inhalation.<br>* Other names: placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to sustained recovery of COVID-19-related signs/symptoms | Sustained recovery of a COVID-19-related sign/symptom is defined as a COVID-19-related sign/symptom score of 0 for 3 consecutive days, i.e., disappearance of COVID-19-related symptoms or return to the status prior to the onset of COVID-19. | Up to Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants who have progression of COVID-19 . | Disease progression is defined as disease severity from mild to moderate or severe or critical, or moderate to severe or critical, or all-cause death | Up to Day 29 | 
| Time to sustained alleviation of COVID-19-related sign/symptom. | Sustained alleviation of COVID-19-related signs/symptoms are defined as the COVID-19-related sign/symptom score from 0 or 1 to 0 at baseline or from 2 or 3 to 1 or 0 at baseline for 3 consecutive days. | Up to Day 29 | 
| Time to sustained recovery of 5 key COVID-19-related sign/symptom | Sustained recovery of a COVID-19-related sign/symptom is defined as a COVID-19-related sign/symptom score of 0 for 3 consecutive days, i.e., disappearance of COVID-19-related symptoms or return to the status prior to the onset of COVID-19. | Up to Day 29 | 
| Time to sustained alleviation of 5 key COVID-19-related sign/symptom | Sustained alleviation of COVID-19-related signs/symptoms are defined as the COVID-19-related sign/symptom score from 0 or 1 to 0 at baseline or from 2 or 3 to 1 or 0 at baseline for 3 consecutive days. | Up to Day 29 | 
| Proportion of participants who experience sustained recovery of COVID-19 sign/symptom | no special description | Day 3 to Day 21 | 
| Proportion of participants who experience sustained alleviation of COVID-19-related sign/symptom | no special description | Day 3 to Day 21 | 
| Duration of each targeted COVID-19-related sign/symptom. | no special description | Up to Day 29 | 
| Time to sustained virus clearance of SARS-CoV-2 in nasopharyngeal swabs | no special description | Up to Day 29 | 
| Changes in SARS-CoV-2 viral load | no special description | Up to Day 29 | 
| Change in EQ-5D-5L index score | The Euroquol Quality of Life 5-Dimension 5-Level Scale(EQ-5D-5L) index score consists of five dimensions: mobility, self-care, daily activities, pain/discomfort, and anxiety/depression. Each dimension has five scales: no difficulty, a little difficulty, moderate difficulty, severe difficulty, and very severe difficulty | Up to Day 29 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), FB2001, Coronavirus