Clinical trial NCT04402866: TD-0903 for ALI Associated With COVID-19
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Lung Injury (ALI) Associated With COVID-19
Lung Inflammation Associated With COVID-19
Keywords: Acute lung injury
ALI
COVID-19
Coronavirus Disease 2019
inflammatory lung conditions
Inflammatory lung disease
ARDS
SARS-CoV-2
Pneumonia
Lead sponsor: Theravance Biopharma
Sponsor class: INDUSTRY
First posted: 2020-05-27
Enrollment: 235
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel group, randomized, double-blind, placebo-controlled
Primary purpose: TREATMENT

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.

Eligibility 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)

Primary outcomes:
measure: Part 2: Number of Respiratory Failure-free Days (RFDs) From Randomization to Day 28
timeFrame: Randomization to Day 28
Secondary outcomes:
measure: Part 2: Change From Baseline in SaO2/FiO2 Ratio on Day 7
timeFrame: Baseline and Day 7
measure: Part 2: Number of Participants in Each Category of the 8-point Ordinal Clinical Status Scale on Days 7, 14, 21, and 28
timeFrame: Days 7, 14, 21 and 28
measure: Part 2: Number of Participants Alive and Respiratory Failure-free on Day 28
timeFrame: Day 28
Other outcomes:
Locations:
city: Duarte
country: United States
facility: Theravance Biopharma Investigational Site
state: California
city: Denver
country: United States
facility: Theravance Biopharma Investigational Site
state: Colorado
city: Sebring
country: United States
facility: Theravance Biopharma Investigational Site
state: Florida
city: Boston
country: United States
facility: Theravance Biopharma Investigational Site
state: Massachusetts
city: Fall River
country: United States
facility: Theravance Biopharma Investigational Site
state: Massachusetts
city: Kalispell
country: United States
facility: Theravance Biopharma Investigational Site
state: Montana
city: Glens Falls
country: United States
facility: Theravance Biopharma Investigational Site
state: New York
city: Hyde Park
country: United States
facility: Theravance Biopharma
state: New York
city: Columbus
country: United States
facility: Theravance Biopharma Investigational Site
state: Ohio
city: Allentown
country: United States
facility: Theravance Biopharma Investigational Site
state: Pennsylvania
city: Bethlehem
country: United States
facility: Theravance Biopharma Investigational Site
state: Pennsylvania
city: Wenatchee
country: United States
facility: Theravance Biopharma Investigational Site
state: Washington
city: Bela Vista
country: Brazil
facility: Theravance Biopharma Investigational Site
city: Botucatu
country: Brazil
facility: Theravance Biopharma Investigational Site
city: Caxias Do Sul
country: Brazil
facility: Theravance Biopharma Investigational Site
city: São José Do Rio Preto
country: Brazil
facility: Theravance Biopharma Investigational Site
city: Helsinki
country: Finland
facility: Theravance Biopharma Investigational Site
city: Turku
country: Finland
facility: Theravance Biopharma Investigational Site
city: Chisinau
country: Moldova, Republic of
facility: Theravance Biopharma Investigational Site
city: Bucharest
country: Romania
facility: Theravance Biopharma Investigational Site
city: Brovary
country: Ukraine
facility: Theravance Biopharma Investigational Site
city: Kyiv
country: Ukraine
facility: Theravance Biopharma Investigational Site
city: Kyiv
country: Ukraine
facility: Theravance Biopharma Investigational Site
city: Manchester
country: United Kingdom
facility: Theravance Biopharma Investigational Site
Study officials:
affiliation: Theravance Biopharma
name: Medical Monitor
role: STUDY_DIRECTOR
References: