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TD-0903 for ALI Associated With 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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04402866
Recruitment Status : Completed
First Posted : May 27, 2020
Last Update Posted : May 19, 2021
Sponsor:
Information provided by (Responsible Party):
Theravance Biopharma

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.

Condition or disease Intervention/treatment Phase
Acute Lung Injury (ALI) Associated With COVID-19 Lung Inflammation Associated With COVID-19 Drug: TD-0903 Drug: Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 235 participants
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
Official Title: 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
Actual Study Start Date : June 24, 2020
Actual Primary Completion Date : April 21, 2021
Actual Study Completion Date : April 21, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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
Drug: TD-0903
Study Drug to be administered by inhalation

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
Drug: TD-0903
Study Drug to be administered by inhalation

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
Drug: TD-0903
Study Drug to be administered by inhalation

Experimental: Part 1: Placebo for MAD
2 out of 8 subjects per cohort (up to 3 cohorts) will be randomized to receive placebo
Drug: Placebo
Placebo to be administered by inhalation

Experimental: Part 2: TD-0903
99 subjects will be randomized to receive TD-0903
Drug: TD-0903
Study Drug to be administered by inhalation

Experimental: Part 2: Placebo
99 subjects will be randomized to receive Placebo
Drug: Placebo
Placebo to be administered by inhalation




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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.


  2. Part 2: Subjects alive and respiratory failure-free [ Time Frame: Day 28 ]
    Proportion of subjects alive and respiratory failure-free on Day 28

  3. Part 2: SaO2/FiO2 ratio [ Time Frame: Baseline, Day 7 ]
    Change from baseline in SaO2/FiO2 ratio on Day 7



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

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): NCT04402866


Locations
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United States, California
Theravance Biopharma Investigational Site
Duarte, California, United States, 91010
United States, Colorado
Theravance Biopharma Investigational Site
Denver, Colorado, United States, 80220
United States, Florida
Theravance Biopharma Investigational Site
Sebring, Florida, United States, 33870
United States, Massachusetts
Theravance Biopharma Investigational Site
Boston, Massachusetts, United States, 02135
Theravance Biopharma Investigational Site
Fall River, Massachusetts, United States, 02720
United States, Montana
Theravance Biopharma Investigational Site
Kalispell, Montana, United States, 59901
United States, New York
Theravance Biopharma Investigational Site
Glens Falls, New York, United States, 12801
Theravance Biopharma
Hyde Park, New York, United States, 11040
United States, Ohio
Theravance Biopharma Investigational Site
Columbus, Ohio, United States, 43214
United States, Pennsylvania
Theravance Biopharma Investigational Site
Allentown, Pennsylvania, United States, 18103
Theravance Biopharma Investigational Site
Bethlehem, Pennsylvania, United States, 18015
United States, Washington
Theravance Biopharma Investigational Site
Wenatchee, Washington, United States, 98801
Brazil
Theravance Biopharma Investigational Site
Bela Vista, Brazil, 01323-001
Theravance Biopharma Investigational Site
Botucatu, Brazil, 18618-686
Theravance Biopharma Investigational Site
Caxias Do Sul, Brazil, 95070-560
Theravance Biopharma Investigational Site
São José Do Rio Preto, Brazil, 15090-000
Finland
Theravance Biopharma Investigational Site
Helsinki, Finland, 00290
Theravance Biopharma Investigational Site
Turku, Finland, 20520
Moldova, Republic of
Theravance Biopharma Investigational Site
Chisinau, Moldova, Republic of, MD-2025
Romania
Theravance Biopharma Investigational Site
Bucharest, Romania, 21105
Ukraine
Theravance Biopharma Investigational Site
Brovary, Ukraine, 07 400
Theravance Biopharma Investigational Site
Kyiv, Ukraine, 01 103
Theravance Biopharma Investigational Site
Kyiv, Ukraine, 01 601
United Kingdom
Theravance Biopharma Investigational Site
Manchester, United Kingdom, M23 9QZ
Sponsors and Collaborators
Theravance Biopharma
Investigators
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Study Director: Medical Monitor Theravance Biopharma
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Responsible Party: Theravance Biopharma
ClinicalTrials.gov Identifier: NCT04402866    
Other Study ID Numbers: 0188
2020-001807-18 ( EudraCT Number )
First Posted: May 27, 2020    Key Record Dates
Last Update Posted: May 19, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Theravance Biopharma, Inc. will not be sharing individual de-identified participant data or other relevant study documents.

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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
Keywords provided by Theravance Biopharma:
Acute lung injury
ALI
COVID-19
Coronavirus Disease 2019
inflammatory lung conditions
Inflammatory lung disease
ARDS
SARS-CoV-2
Pneumonia
Additional relevant MeSH terms:
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COVID-19
Pneumonia
Lung Injury
Acute Lung Injury
Inflammation
Respiratory Tract Infections
Infections
Pneumonia, Viral
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Wounds and Injuries
Pathologic Processes
Thoracic Injuries