TD-0903 for ALI Associated With COVID-19

NCT ID: NCT04402866

Last Updated: 2022-03-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 235 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-24
• Study Completion Date: 2021-04-21

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.

Conditions

Acute Lung Injury (ALI) Associated With COVID-19; Lung Inflammation Associated With COVID-19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Part 1: TD-0903 - MAD Dose A

6 out of 8 subjects per cohort will be randomized to receive TD-0903 MAD Dose A

Group Type: EXPERIMENTAL

TD-0903

Intervention Type: DRUG

Study Drug to be administered by inhalation

Part 1: TD-0903 - MAD Dose B

6 out of 8 subjects per cohort will be randomized to receive TD-0903 MAD Dose B

Group Type: EXPERIMENTAL

TD-0903

Intervention Type: DRUG

Study Drug to be administered by inhalation

Part 1: TD-0903 - MAD Dose C

6 out of 8 subjects per cohort will be randomized to receive TD-0903 MAD Dose C

Group Type: EXPERIMENTAL

TD-0903

Intervention Type: DRUG

Study Drug to be administered by inhalation

Part 1: Placebo for MAD

2 out of 8 subjects per cohort (up to 3 cohorts) will be randomized to receive placebo

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Placebo to be administered by inhalation

Part 2: TD-0903

99 subjects will be randomized to receive TD-0903

Group Type: EXPERIMENTAL

TD-0903

Intervention Type: DRUG

Study Drug to be administered by inhalation

Part 2: Placebo

99 subjects will be randomized to receive Placebo

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Placebo to be administered by inhalation

Interventions

TD-0903

Study Drug to be administered by inhalation

Intervention Type: DRUG

Placebo

Placebo to be administered by inhalation

Intervention Type: DRUG

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Theravance Biopharma

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Theravance Biopharma

Locations

Theravance Biopharma Investigational Site

Duarte, California, United States

Theravance Biopharma Investigational Site

Denver, Colorado, United States

Theravance Biopharma Investigational Site

Sebring, Florida, United States

Theravance Biopharma Investigational Site

Boston, Massachusetts, United States

Theravance Biopharma Investigational Site

Fall River, Massachusetts, United States

Theravance Biopharma Investigational Site

Kalispell, Montana, United States

Theravance Biopharma Investigational Site

Glens Falls, New York, United States

Theravance Biopharma

Hyde Park, New York, United States

Theravance Biopharma Investigational Site

Columbus, Ohio, United States

Theravance Biopharma Investigational Site

Allentown, Pennsylvania, United States

Theravance Biopharma Investigational Site

Bethlehem, Pennsylvania, United States

Theravance Biopharma Investigational Site

Wenatchee, Washington, United States

Theravance Biopharma Investigational Site

Bela Vista, , Brazil

Theravance Biopharma Investigational Site

Botucatu, , Brazil

Theravance Biopharma Investigational Site

Caxias do Sul, , Brazil

Theravance Biopharma Investigational Site

São José do Rio Preto, , Brazil

Theravance Biopharma Investigational Site

Helsinki, , Finland

Theravance Biopharma Investigational Site

Turku, , Finland

Theravance Biopharma Investigational Site

Chisinau, , Moldova

Theravance Biopharma Investigational Site

Bucharest, , Romania

Theravance Biopharma Investigational Site

Brovary, , Ukraine

Theravance Biopharma Investigational Site

Kyiv, , Ukraine

Theravance Biopharma Investigational Site

Kyiv, , Ukraine

Theravance Biopharma Investigational Site

Manchester, , United Kingdom

Countries

United States; Brazil; Finland; Moldova; Romania; Ukraine; United Kingdom

References

Belperio J, Nguyen T, Lombardi DA, Bogus M, Moskalenko V, Singh D, Haumann B, Bourdet DL, Kaufman E, Pfeifer ND, Thompson CG, Woo J, Moran EJ, Saggar R. Efficacy and safety of an inhaled pan-Janus kinase inhibitor, nezulcitinib, in hospitalised patients with COVID-19: results from a phase 2 clinical trial. BMJ Open Respir Res. 2023 Jul;10(1):e001627. doi: 10.1136/bmjresp-2023-001627.

Reference Type: DERIVED

PMID: 37460276 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2020-001807-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

0188

Identifier Type: -

Identifier Source: org_study_id