Study of TB006 in Outpatient Patients With Mild to Moderate COVID-19

Study Overview
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Brief Summary
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TB006, a monoclonal antibody, is an anti-inflammatory and anti-fibrotic agent that reduces the severity of underlying diseases in COVID-19 patients. The primary objective of TB006 treatment is to decrease the potential acute severe deterioration in outpatient COVID-19 patients with underlying diseases, such as diabetes, hypertension, and cancer. TB006 has been developed to treat the ambulatory patients with diagnosed mild to moderate COVID-19 who are considered at low risk for severe disease or hospitalization.

Detailed Description
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TB006, a monoclonal antibody, is an anti-inflammatory and anti-fibrotic agent that reduces the severity of underlying diseases in COVID-19 patients. The primary objective of TB006 treatment is to decrease the potential acute severe deterioration in outpatient COVID-19 patients with underlying diseases, such as diabetes, hypertension, and cancer. TB006 has been developed to treat the ambulatory patients with diagnosed mild to moderate COVID-19 who are considered at low risk for severe disease or hospitalization. In the single ascending dose study, the dosages of 5 mg/kg   50 mg/kg will be investigated in patients with mild to moderate COVID-19, and will be administered to patients over 60 minutes after dilution in 0.9% Sodium Chloride Injection, USP (normal saline) to a final volume of 250 mL. The primary objective of the SAD study is to evaluate the safety and tolerability of single ascending doses of TB006 vs placebo administered via i.v. infusion in outpatient patients with mild-to-moderate COVID-19 and to determine the dose recommended for Phase Ib study.

Official Title
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A Phase I, First-In-Human, Randomized, Single Ascending Dose Study of TB006 in Outpatient Patients With Mild to Moderate COVID-19

Conditions
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Covid19

Intervention / Treatment
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* Drug: TB006
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to provide written informed consent prior to performing study procedures (or legally authorized representative able to provide consent on the patient's behalf). Age ≥ 18 years A positive Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection confirmed by polymerase chain reaction (PCR) test or an equivalent test ≤ 3 days before randomization Patients with mild to moderate COVID-19 experiencing any of the following symptoms: Mild (without shortness of breath or dyspnea): Fever, cough, sore throat, malaise, headache, muscle pain, gastrointestinal symptoms Moderate: Any symptom of mild illness, shortness of breath with excursion, clinically suggestive of moderate illness with COVID-19, such as respiratory rate ≥ 20 breaths per minute, saturation of oxygen (SpO2) > 93% on room air at sea level, heart rate ≥ 90 beats per minute At low risk for progressing to severe COVID-19 and/or hospitalization. Adequate organ function at screening as evidenced by: Hemoglobin > 10.9 g/dL Absolute neutrophil count (ANC) > 1.0 × 10^9/L Platelets > 125 × 10^9/L Alanine Aminotransferase (ALT) or aspartate aminotransferase (AST) < 1.25 × upper limit of normal (ULN) Creatinine clearance > 90 mL/min using the Cockcroft-Gault formula for patients ≥ 18 years of age [Cockcroft 1976] Normal electrocardiogram with QTcF of ≤ 450 ms Exclusion Criteria: Participation in any other clinical trial of an experimental treatment for COVID-19 Clinical signs indicative of Severe or Critical Illness Severity SEVERE: Any symptom of severe, systematic illness, including moderate illness, shortness of breath, or respiratory distress Clinically suggestive of severe illness with COVID-19, such as respiratory rate ≥ 30 breaths per minute, heart rate ≥ 125 per minute, saturation of oxygen (SpO2) ≤ 93% on room air at sea level, or PaO2/FiO2 < 300 CRITICAL ILLNESS (one of the following): Respiratory failure defined based on resource utilization requiring at least one of the following: Endotracheal intubation and mechanical ventilation, oxygen delivered by high483 flow nasal cannula (heated, humidified, oxygen delivered via reinforced nasal cannula at flow rates > 20 L/min with fraction of delivered oxygen ≥ 0.5) Noninvasive positive pressure ventilation, ECMO, or clinical diagnosis of respiratory failure (i.e., clinical need for one of the preceding therapies, but preceding therapies not able to be administered in setting of resource limitation) Shock (defined by systolic blood pressure < 90 mm Hg, or diastolic blood pressure < 60 mm Hg or requiring vasopressors) Multi-organ dysfunction/failure Have a history of a positive SARS-CoV-2 serology test Evidence of shock (defined by systolic blood pressure < 90 mm Hg, or diastolic blood pressure < 60 mm Hg or requiring vasopressors) Patients who are hospitalized due to COVID-19 Patients who required oxygen therapy due to COVID-19 Patients who required mechanical ventilation or anticipated impending need for mechanical ventilation Receiving V-V ECMO ≥ 5 days, or any duration of V-A ECMO Have a history of convalescent COVID-19 plasma treatment Women who are pregnant or breastfeeding Male or female of childbearing potential who has plans to become pregnant during the study period and for six months after the clinical study or who is not willing to take appropriate contraceptive measures (e.g., concomitant use of a spermicidal agent, barrier contraceptive, or/and intrauterine contraceptive) Viral disease (HIV, HBV, HCV, etc.) other than COVID-19 that are not adequately controlled or require administration of other antiviral agents or medications that could potentially interact with TB006 Patients with a history or current evidence of any concomitant condition, therapy, or laboratory abnormality that, in the opinion of the investigator, might confound the results of the trial, interfere with the patient's participation and compliance

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
Interventional Model Description: Single Ascending Dose
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TB006<br>During the SAD study, subjects will receive a single dose of TB006 (at the dosage level of 10   50 mg/kg) administered via i.v. infusion for 60 mins. In addition, a sentinel cohort of 5 mg/kg will be open for enrollment and double-blinded randomization first, with 2 patients randomized to active/TB006 arm, to assess preliminary safety and tolerability of study drug, and to determine cohort expansion and dose escalation. Upon the completion of sentinel cohort and all subjects are safe and well tolerate study treatment, regular dose escalation will start. | Drug: TB006<br>* TB006 monoclonal antibody<br>|
| Placebo Comparator: Placebo<br>During the SAD study, subjects will receive a single dose of the placebo administered via i.v. infusion for 60 mins. In addition, the corresponding sentinel placebo group will include 1 patient to placebo arm. Upon the completion of sentinel cohort and all subjects are safe and well tolerate study treatment, regular dose escalation will start. | Other: Placebo<br>* Placebo i.v. infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment emergent adverse events | Evaluated as per DAIDS v2.1 | Baseline to Day 85 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameters of TB006: AUC(0-last) | - Area under the plasma concentration curve over time (hr*µg/mL) | Day 1 to Day 85 | 
| Pharmacokinetic parameters of TB006: Cmax | - Maximum concentration of TB006 (µg/mL) | Day 1 to Day 85 | 
| Pharmacokinetic parameters of TB006: Tmax | - The amount of time that TB006 is present at the maximum concentration (hours) | Day 1 to Day 85 | 
| Pharmacokinetic parameters of TB006: T1/2 | - Half life of TB006 (hours) | Day 1 to Day 85 | 
| Immunogenicity | - Anti-drug antibodies (ADA) | Day 1 to Day 85 | 
| Preliminary Efficacy: Viral shedding change | Change from baseline in viral shedding from Day 1 to Day 28, as measured by RT-qPCR | Day 1 to Day 28 | 
| Preliminary Efficacy: Viral shedding change at each visit | Change from baseline in viral shedding at each visit through Day 28, as measured by RT-qPCR | Baseline to Day 28 | 
| Preliminary Efficacy: Time to viral shedding clearance | Measure the time to viral shedding clearance | Baseline to Day 85 | 
| Preliminary Efficacy: Proportion of treated patients with ≥ 1 COVID-19 related medically-attended visit through Day 28 | Proportion of treated patients with ≥ 1 COVID-19 related medically-attended visit through Day 28 | Baseline to Day 28 | 
| Preliminary Efficacy: Total number of COVID-19 related medically-attended visits | Number of COVID-19 related medically-attended visits during study | Baseline to Day 28 | 
| Preliminary Efficacy: Proportion of treated patients admitted to a hospital due to COVID-19 | Proportion of patients admitted to a hospital by Day 28 | Baseline to Day 28 | 
| Preliminary Efficacy: Time to sustained clinical recovery from baseline | Time to sustained clinical recovery from baseline to end of follow-up visits | Baseline to Day 85 | 
| Preliminary Efficacy: Clinical improvement from baseline at each visit through Day 28 (in patients with or without underlying comorbidities | Measured by change in score according to the World Health Organization (WHO) ordinal scale, ranging from 0 (uninfected) to 8 (dead) | Baseline to Day 28 |