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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Covid19
• Intervention / Treatment: Drug: TB006; Other: Placebo

Detailed Description

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.

• Study Type: Interventional
• Phase: Phase 1

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. 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).
2. Age ≥ 18 years
3. 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

4. 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
5. At low risk for progressing to severe COVID-19 and/or hospitalization.

6. 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]
7. Normal electrocardiogram with QTcF of ≤ 450 ms

Exclusion Criteria:

1. Participation in any other clinical trial of an experimental treatment for COVID-19

2. 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:

     1. 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)
     2. 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
3. Have a history of a positive SARS-CoV-2 serology test
4. Evidence of shock (defined by systolic blood pressure < 90 mm Hg, or diastolic blood pressure < 60 mm Hg or requiring vasopressors)
5. Patients who are hospitalized due to COVID-19
6. Patients who required oxygen therapy due to COVID-19
7. Patients who required mechanical ventilation or anticipated impending need for mechanical ventilation
8. Receiving V-V ECMO ≥ 5 days, or any duration of V-A ECMO
9. Have a history of convalescent COVID-19 plasma treatment
10. Women who are pregnant or breastfeeding
11. 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)
12. 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
13. 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TB006; 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; TB006 monoclonal antibody
Placebo Comparator: Placebo; 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; Placebo i.v. infusion

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacodynamics biomarkers: Troponins	Change in cardiac biomarkers (ng/mL)	Baseline to Day 28
Pharmacodynamics biomarkers: N-terminal pro B-type natriuretic peptide (NT-proBNP)	Change in cardiac biomarkers (pg/mL)	Baseline to Day 28
Pharmacodynamics biomarkers: Creatine kinase-MB (CK-MB)	Change in cardiac biomarkers (ng/mL)	Baseline to Day 28
Pharmacodynamics biomarkers: Change in neutrophil-lymphocyte ratio (NLR)	Monitor potential inflammation activity	Baseline to Day 28
Pharmacodynamics biomarkers: IL-6	- Change in cytokine measurement (pg/mL)	Baseline to Day 28
Pharmacodynamics biomarkers: IL-2	- Change in cytokine measurement (pg/mL)	Baseline to Day 28
Pharmacodynamics biomarkers: IL-7	- Change in cytokine measurement (pg/mL)	Baseline to Day 28
Pharmacodynamics biomarkers: IL-8	- Change in cytokine measurement (pg/mL)	Baseline to Day 28
Pharmacodynamics biomarkers: IL-1β	- Change in cytokine measurement (pg/mL)	Baseline to Day 28
Pharmacodynamics biomarkers: IFNgamma	- Change in cytokine measurement (pg/mL)	Baseline to Day 28
Pharmacodynamics biomarkers: TNFα	- Change in cytokine measurement (pg/mL)	Baseline to Day 28
Pharmacodynamics biomarkers: IL-10	- Change in cytokine measurement (pg/mL)	Baseline to Day 28
Pharmacodynamics biomarkers: MIP-1α/β	- Change in cytokine measurement (pg/mL)	Baseline to Day 28
Pharmacodynamics biomarkers: C-reactive protein (CRP)	- Change in serum and plasma biomarkers (mg/L)	Baseline to Day 28
Pharmacodynamics biomarkers: Ferritin	- Change in serum and plasma biomarkers (mg/L)	Baseline to Day 28
Pharmacodynamics biomarkers: D-dimer	- Change in serum and plasma biomarkers (mg/L)	Baseline to Day 28
Virology	- Change in viral sequencing, resistance, infectivity using RT-qPCR	Baseline to Day 85
Patient Report Outcomes (PRO): Sponsor developed patient self-report COVID-19 symptom survey (PSRSS-C19)	- Change from baseline to Day 28 and safety follow-up visit in score ranging from 0 (none) to 3 (severe)	Baseline to Day 85
Patient Report Outcomes (PRO): Patient Global Impression of Severity (PGI-S) survey	- Change from baseline to Day 28 and safety follow-up visit in score ranging from 0 (non) to 4 (very severe)	Baseline to Day 85
Patient Report Outcomes (PRO): Patient Global Impression of Change (PGI-C) survey	- Change from baseline to Day 28 and safety follow-up visit in score ranging from 0 (much better) and 4 (much worse)	Baseline to Day 85

Collaborators and Investigators

• Sponsor: TrueBinding, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2021
• Primary Completion (Actual): September 1, 2021
• Study Completion (Actual): September 1, 2021

Study Registration Dates

• First Submitted: March 11, 2021
• First Submitted That Met QC Criteria: March 15, 2021
• First Posted (Actual): March 16, 2021

Study Record Updates

• Last Update Posted (Actual): May 18, 2022
• Last Update Submitted That Met QC Criteria: May 11, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• 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: TB006C1101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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