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Trial record 1 of 1 for:    NCT04402866
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TD-0903 for ALI Associated With COVID-19

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ClinicalTrials.gov Identifier: NCT04402866
Recruitment Status : Recruiting
First Posted : May 27, 2020
Last Update Posted : October 19, 2020
Sponsor:
Information provided by (Responsible Party):
Theravance Biopharma

Tracking Information
First Submitted Date  ICMJE May 22, 2020
First Posted Date  ICMJE May 27, 2020
Last Update Posted Date October 19, 2020
Actual Study Start Date  ICMJE June 24, 2020
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 15, 2020)
Part 2: Respiratory Failure-Free Days (RFDs) [ Time Frame: Baseline through Day 28 ]
Number of Respiratory Failure-Free Days (RFDs) from randomization through Day 28
Original Primary Outcome Measures  ICMJE
 (submitted: May 22, 2020)
  • Part 2: SaO2/FiO2 ratio [ Time Frame: Baseline, Day 7 ]
    Change from baseline in SaO2/FiO2 ratio
  • Part 2: Ventilator-free Days (VFDs) [ Time Frame: Baseline through Day 28 ]
    Number of days the subject was not using invasive mechanical ventilation or non-invasive positive pressure ventilation
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 15, 2020)
  • Part 2: Clinical Status Scale [ Time Frame: Day 7, 14, 21 and 28 ]
    Proportion of subjects in each category of the 8-point Clinical Status scale. The Clinical Status scale contains 8 different categories that are each assigned a numeric score. The values range from 1 (representing 'Not hospitalized, no limitations on activities') to 8 (representing 'Death'). The various measures describe hospitalization status and the various limitations and requirements for oxygen support.
  • Part 2: Subjects alive and respiratory failure-free [ Time Frame: Day 28 ]
    Proportion of subjects alive and respiratory failure-free on Day 28
  • Part 2: SaO2/FiO2 ratio [ Time Frame: Baseline, Day 7 ]
    Change from baseline in SaO2/FiO2 ratio on Day 7
Original Secondary Outcome Measures  ICMJE
 (submitted: May 22, 2020)
  • Part 2: Intensive Care Unit Free Days (ICU-free) [ Time Frame: Baseline through Day 28 ]
    Number of days the subject was not in the ICU
  • Part 2: AUC in SaO2/FiO2 ratio [ Time Frame: Baseline through Day 7 ]
    Area under the plasma concentration-time curve (AUC) in SaO2/FiO2 ratio
  • Part 2: SaO2/FiO2 ratio [ Time Frame: Baseline, Day 5 ]
    Change from baseline in SaO2/FiO2 ratio
  • Part 2: SaO2/FiO2 ratio > 315 [ Time Frame: Day 5, Day 7 ]
    Proportion of subjects with a SaO2/FiO2 ratio > 315
  • Part 2: Subjects Discharged [ Time Frame: Day 7, 14, 21 and 28 ]
    Proportion of subjects discharged
  • Part 2: Hospital Discharge [ Time Frame: Baseline through up to Day 28 ]
    Time to hospital discharge
  • Part 2: Mortality Rate [ Time Frame: Day 28 ]
    The subject mortality rate (all causes)
  • Part 2: Modified Borg Dyspnea Score [ Time Frame: Baseline through Day 7 ]
    Change from baseline in the modified Borg Dyspnea Score. The modified Borg Dyspnea Score is based on a 10-point scale that measures shortness of breath. Scores range from 0 (nothing at all, no shortness of breath) to 10 (maximal shortness of breath).
  • Part 2: Clinical Status Scale [ Time Frame: Day 7, 14, 21 and 28 ]
    Proportion of subjects in each category of the Clinical Status scale. The Clinical Status scale contains 6 different categories that are each assigned a numeric score. The values range from 1 (representing 'Not hospitalized'), 2 (hospitalized, not requiring supplemental oxygen), 3 (hospitalized, requiring low-flow oxygen supplementation), 4 (hospitalized, on non-invasive positive pressure ventilation or high-flow oxygen supplementation), 5 (hospitalized, on invasive mechanical ventilation, 6 (Death).
  • Part 2: Vital Status [ Time Frame: Day 7, 14, 21 and 28 ]
    Proportion of subjects in each category of Vital Status, where the categories are defined as death, discharge, or hospitalized.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE TD-0903 for ALI Associated With COVID-19
Official Title  ICMJE A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-group, Multi-center Study of an Inhaled Pan-Janus Kinase Inhibitor, TD-0903, to Treat Symptomatic Acute Lung Injury Associated With COVID-19
Brief Summary This Phase 2 study will evaluate the efficacy, safety, pharmacodynamics and pharmacokinetics of inhaled TD-0903 compared with a matching placebo in combination with standard of care (SOC) in hospitalized patients with confirmed COVID-19 associated acute lung injury and impaired oxygenation.
Detailed Description

Part 1 of the study includes up to 3 ascending dose cohorts, each comprised of 8 subjects (6 receiving TD-0903 and 2 receiving placebo).

Part 2 of the study will evaluate one dose of TD-0903 (selected based on the data from Part 1) as compared with placebo. Part 2 is targeting 198 subjects total.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Parallel group, randomized, double-blind, placebo-controlled
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:
Pharmacist & Sponsor are not blinded for Part 1. Sponsor is blinded for Part 2. Pharmacist is not blinded for Part 2.
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Lung Injury (ALI) Associated With COVID-19
  • Lung Inflammation Associated With COVID-19
Intervention  ICMJE
  • Drug: TD-0903
    Study Drug to be administered by inhalation
  • Drug: Placebo
    Placebo to be administered by inhalation
Study Arms  ICMJE
  • Experimental: Part 1: TD-0903 - MAD Dose A
    6 out of 8 subjects per cohort will be randomized to receive TD-0903 MAD Dose A
    Intervention: Drug: TD-0903
  • Experimental: Part 1: TD-0903 - MAD Dose B
    6 out of 8 subjects per cohort will be randomized to receive TD-0903 MAD Dose B
    Intervention: Drug: TD-0903
  • Experimental: Part 1: TD-0903 - MAD Dose C
    6 out of 8 subjects per cohort will be randomized to receive TD-0903 MAD Dose C
    Intervention: Drug: TD-0903
  • Experimental: Part 1: Placebo for MAD
    2 out of 8 subjects per cohort (up to 3 cohorts) will be randomized to receive placebo
    Intervention: Drug: Placebo
  • Experimental: Part 2: TD-0903
    99 subjects will be randomized to receive TD-0903
    Intervention: Drug: TD-0903
  • Experimental: Part 2: Placebo
    99 subjects will be randomized to receive Placebo
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 15, 2020)
222
Original Estimated Enrollment  ICMJE
 (submitted: May 22, 2020)
159
Estimated Study Completion Date  ICMJE February 2021
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Willing and able to provide written informed consent on their own prior to performing study procedures. In the U.K., subject assent or proxy consent as per local site procedures, may also be acceptable if both a clinician and second health professional attest that the subject understands the risks and potential benefits of the study and elects to proceed. Outside the U.K., written informed consent may only be obtained from the subject or legally authorized representative. In the event the subject loses capacity during the study, the subject consents to continued participation, except where this is not clinically indicated.
  • Willing and able to comply with study-related procedures/assessments
  • Age 18 to 80 years old
  • Hospitalized (or documentation of a plan to admit to the hospital if the subject is in an emergency department) and requiring supplemental oxygen to maintain saturation > 90%
  • A diagnosis of symptomatic COVID-19 defined as a positive test for SARS-CoV-2 RNA detected by RT-PCR on a sample from the upper respiratory tract (e.g., nasopharyngeal, nasal, or oropharyngeal swab) collected < 72 hours prior to randomization
  • Onset of COVID-19 -related symptoms > 2 days and </= 10 days prior to hospital admission

Exclusion Criteria:

  • Subjects currently receiving invasive mechanical ventilation
  • Presence or suspicion of active malignancy with the exception of cancer in situ (e.g., skin cancer)
  • Evidence of serious active infection other than COVID-19
  • Current diagnosis of human immunodeficiency virus, hepatitis B or C
  • In the opinion of the investigator, unlikely to survive for > 24 hours from enrollment
  • Women who are pregnant or might be pregnant, or who are currently breast-feeding. Subjects must agree to not donate ova or sperm through 30 days after the last dose of study medication
  • Presence of significant comorbidity that, in the opinion of the investigator, predisposes the subject to mortality. Such conditions might include: a. New York Heart Association class IV Heart Failure b. Hepatic dysfunction (i.e., AST or ALT >3x upper limit of normal) c. Renal dysfunction (i.e., estimated glomerular filtration rate (eGFR) < 50mL/min) or receiving renal replacement therapy
  • Presence of septic shock at time of enrollment
  • Hemoglobin < 80 g/L
  • Evidence of neutropenia (i.e., absolute neutrophil count < 1000 cells/uL), lymphopenia (i.e., absolute lymphocyte count < 200 cells/uL) or thrombocytopenia (i.e.Platelets < 50×10^9/L)
  • Hypersensitivity to TD-0903 or its components, or to other JAK inhibitors
  • Treatment with anti-IL 6 (e.g., tocilizumab, sarilumab), anti-IL-6R antagonists (e.g., abatacept), JAK inhibitors (e.g., baricitinib, tofacitinib) supplemental interferon therapy, or tyrosine kinase inhibitors (e.g., erlotinib, gefinitib) in the past 30 days, or plans to receive a JAK inhibitor during the study period
  • Current treatment with conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs)/immunosuppressive agents including:

    1. Methotrexate, cyclosporine, mycophenolate, tacrolimus, penicillamine, or sulfasalazine within 2 weeks prior to enrollment
    2. Azathioprine or cyclophosphamide within 12 weeks prior to enrollment
    3. Monoclonal antibodies targeting B cells (e.g., rituximab) within 12 weeks prior to enrollment
    4. Tumor necrosis factor-alpha (TNFα)) inhibitors within 4 weeks prior to enrollment
  • Participating in other clinical trials involving any other experimental treatment for COVID-19, except in the context of a single-arm antiviral or convalescent plasma compassionate-use protocol
  • Subjects with active or incompletely treated pulmonary tuberculosis, or known history of non-tuberculosis mycobacterium over past 12 months
  • Subject requires continuous oxygen supplementation for underlying cardio-respiratory history in the past 90 days
  • Body Mass Index ≥40 kg/m2
  • Receipt of live vaccine (i.e., live attenuated) in the 4 weeks prior to visit 1 or plans to receive a live vaccine (or live attenuated) during the study period. Note: Use of non-live (inactivated) vaccinations is allowed for all subjects
  • History of venous thromboembolism (VTE), deep venous thrombosis (DVT), Pulmonary Embolism (PE) or known hypercoagulable disorder (e.g., factor V Leiden, antiphospholipid antibody syndrome, protein C or S deficiency)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Theravance Biopharma Call Center 1-855-633-8479 medinfo@theravance.com
Listed Location Countries  ICMJE Moldova, Republic of,   Romania,   Ukraine,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04402866
Other Study ID Numbers  ICMJE 0188
2020-001807-18 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: Theravance Biopharma, Inc. will not be sharing individual de-identified participant data or other relevant study documents.
Responsible Party Theravance Biopharma
Study Sponsor  ICMJE Theravance Biopharma
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Monitor Theravance Biopharma
PRS Account Theravance Biopharma
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP