Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 2 for:    TB006
Previous Study | Return to List | Next Study

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04801056
Recruitment Status : Not yet recruiting
First Posted : March 16, 2021
Last Update Posted : March 16, 2021
Sponsor:
Information provided by (Responsible Party):
TrueBinding, Inc.

Brief Summary:
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 high risk for severe disease or hospitalization. The preferred population includes patients with elevated cytokines (e.g., IL-6) at baseline and patients with underlying diseases at baseline including diabetes mellitus, cardiovascular diseases (such as hypertension), and cancer.

Condition or disease Intervention/treatment Phase
Covid19 Drug: TB006 Other: Placebo Phase 1

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 high risk for severe disease or hospitalization. The preferred population includes patients with elevated cytokines (e.g., IL-6) at baseline and patients with underlying diseases at baseline including diabetes mellitus, cardiovascular diseases (such as hypertension), and cancer.

In the single ascending dose study, the dosages of 10 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 27 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Single Ascending Dose
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase I, First-In-Human, Randomized, Single Ascending Dose Study of TB006 in Outpatient Patients With Mild to Moderate COVID-19
Estimated Study Start Date : March 2021
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : September 2021

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




Primary Outcome Measures :
  1. Treatment emergent adverse events [ Time Frame: Baseline to Day 85 ]
    Evaluated as per DAIDS v2.1


Secondary Outcome Measures :
  1. Pharmacokinetic parameters of TB006: AUC(0-last) [ Time Frame: Day 1 to Day 85 ]
    - Area under the plasma concentration curve over time (hr*µg/mL)

  2. Pharmacokinetic parameters of TB006: Cmax [ Time Frame: Day 1 to Day 85 ]
    - Maximum concentration of TB006 (µg/mL)

  3. Pharmacokinetic parameters of TB006: Tmax [ Time Frame: Day 1 to Day 85 ]
    - The amount of time that TB006 is present at the maximum concentration (hours)

  4. Pharmacokinetic parameters of TB006: T1/2 [ Time Frame: Day 1 to Day 85 ]
    - Half life of TB006 (hours)

  5. Immunogenicity [ Time Frame: Day 1 to Day 85 ]
    - Anti-drug antibodies (ADA)

  6. Preliminary Efficacy: Viral shedding change [ Time Frame: Day 1 to Day 28 ]
    Change from baseline in viral shedding from Day 1 to Day 28, as measured by RT-qPCR

  7. Preliminary Efficacy: Viral shedding change at each visit [ Time Frame: Baseline to Day 28 ]
    Change from baseline in viral shedding at each visit through Day 28, as measured by RT-qPCR

  8. Preliminary Efficacy: Time to viral shedding clearance [ Time Frame: Baseline to Day 85 ]
    Measure the time to viral shedding clearance

  9. Preliminary Efficacy: Proportion of treated patients with ≥ 1 COVID-19 related medically-attended visit through Day 28 [ Time Frame: Baseline to Day 28 ]
    Proportion of treated patients with ≥ 1 COVID-19 related medically-attended visit through Day 28

  10. Preliminary Efficacy: Total number of COVID-19 related medically-attended visits [ Time Frame: Baseline to Day 28 ]
    Number of COVID-19 related medically-attended visits during study

  11. Preliminary Efficacy: Proportion of treated patients admitted to a hospital due to COVID-19 [ Time Frame: Baseline to Day 28 ]
    Proportion of patients admitted to a hospital by Day 28

  12. Preliminary Efficacy: Time to sustained clinical recovery from baseline [ Time Frame: Baseline to Day 85 ]
    Time to sustained clinical recovery from baseline to end of follow-up visits

  13. Preliminary Efficacy: Clinical improvement from baseline at each visit through Day 28 (in patients with or without underlying comorbidities [ Time Frame: Baseline to Day 28 ]
    Measured by change in score according to the World Health Organization (WHO) ordinal scale, ranging from 0 (uninfected) to 8 (dead)


Other Outcome Measures:
  1. Pharmacodynamics biomarkers: Troponins [ Time Frame: Baseline to Day 28 ]
    Change in cardiac biomarkers (ng/mL)

  2. Pharmacodynamics biomarkers: N-terminal pro B-type natriuretic peptide (NT-proBNP) [ Time Frame: Baseline to Day 28 ]
    Change in cardiac biomarkers (pg/mL)

  3. Pharmacodynamics biomarkers: Creatine kinase-MB (CK-MB) [ Time Frame: Baseline to Day 28 ]
    Change in cardiac biomarkers (ng/mL)

  4. Pharmacodynamics biomarkers: Change in neutrophil-lymphocyte ratio (NLR) [ Time Frame: Baseline to Day 28 ]
    Monitor potential inflammation activity

  5. Pharmacodynamics biomarkers: IL-6 [ Time Frame: Baseline to Day 28 ]
    - Change in cytokine measurement (pg/mL)

  6. Pharmacodynamics biomarkers: IL-2 [ Time Frame: Baseline to Day 28 ]
    - Change in cytokine measurement (pg/mL)

  7. Pharmacodynamics biomarkers: IL-7 [ Time Frame: Baseline to Day 28 ]
    - Change in cytokine measurement (pg/mL)

  8. Pharmacodynamics biomarkers: IL-8 [ Time Frame: Baseline to Day 28 ]
    - Change in cytokine measurement (pg/mL)

  9. Pharmacodynamics biomarkers: IL-1β [ Time Frame: Baseline to Day 28 ]
    - Change in cytokine measurement (pg/mL)

  10. Pharmacodynamics biomarkers: IFNgamma [ Time Frame: Baseline to Day 28 ]
    - Change in cytokine measurement (pg/mL)

  11. Pharmacodynamics biomarkers: TNFα [ Time Frame: Baseline to Day 28 ]
    - Change in cytokine measurement (pg/mL)

  12. Pharmacodynamics biomarkers: IL-10 [ Time Frame: Baseline to Day 28 ]
    - Change in cytokine measurement (pg/mL)

  13. Pharmacodynamics biomarkers: MIP-1α/β [ Time Frame: Baseline to Day 28 ]
    - Change in cytokine measurement (pg/mL)

  14. Pharmacodynamics biomarkers: C-reactive protein (CRP) [ Time Frame: Baseline to Day 28 ]
    - Change in serum and plasma biomarkers (mg/L)

  15. Pharmacodynamics biomarkers: Ferritin [ Time Frame: Baseline to Day 28 ]
    - Change in serum and plasma biomarkers (mg/L)

  16. Pharmacodynamics biomarkers: D-dimer [ Time Frame: Baseline to Day 28 ]
    - Change in serum and plasma biomarkers (mg/L)

  17. Virology [ Time Frame: Baseline to Day 85 ]
    - Change in viral sequencing, resistance, infectivity using RT-qPCR

  18. Patient Report Outcomes (PRO): Sponsor developed patient self-report COVID-19 symptom survey (PSRSS-C19) [ Time Frame: Baseline to Day 85 ]
    - Change from baseline to Day 28 and safety follow-up visit in score ranging from 0 (none) to 3 (severe)

  19. Patient Report Outcomes (PRO): Patient Global Impression of Severity (PGI-S) survey [ Time Frame: Baseline to Day 85 ]
    - Change from baseline to Day 28 and safety follow-up visit in score ranging from 0 (non) to 4 (very severe)

  20. Patient Report Outcomes (PRO): Patient Global Impression of Change (PGI-C) survey [ Time Frame: Baseline to Day 85 ]
    - Change from baseline to Day 28 and safety follow-up visit in score ranging from 0 (much better) and 4 (much worse)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 high risk for progressing to severe COVID-19 and/or hospitalization. High risk patients are defined as meeting at least one of the following criteria:

    • Have diabetes
    • Have hypertension
    • Have cancer
    • Body Mass Index (BMI) ≥ 35
    • Have chronic kidney disease
    • Are ≥ 65 years of age
    • Are ≥ 55 years of age AND have
    • Cardiovascular disease such as hypertension, or
    • Chronic obstructive pulmonary disease/other chronic respiratory disease
  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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04801056


Contacts
Layout table for location contacts
Contact: Dongxu Sun, PhD (650) 785-0225 ext 1 dsun@truebinding.com

Locations
Layout table for location information
United States, Ohio
Gabrail Cancer Center
Canton, Ohio, United States, 44718
Contact: Carrie Smith, RN         
Principal Investigator: Nashat Gabrail, MD         
Sponsors and Collaborators
TrueBinding, Inc.
Layout table for additonal information
Responsible Party: TrueBinding, Inc.
ClinicalTrials.gov Identifier: NCT04801056    
Other Study ID Numbers: TB006C1101
First Posted: March 16, 2021    Key Record Dates
Last Update Posted: March 16, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No