Acute Lung Injury (ALI) Associated With COVID-19Phase 2NCT04402866
TD-0903 for ALI Associated With COVID-19
A Phase 2 study testing TD-0903 in people with Acute Lung Injury (ALI) Associated With COVID-19 and Lung Inflammation Associated With COVID-19, run by Theravance Biopharma at 24 sites in 7 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Acute Lung Injury (ALI) Associated With COVID-19, Lung Inflammation Associated With COVID-19
- What is being tested?
- TD-0903
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 235 participants
- Where
- 24 sitesin 7 countries
- Study dates
- 24 Jun 2020to 21 Apr 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 23Show fewer
- 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:
- Methotrexate, cyclosporine, mycophenolate, tacrolimus, penicillamine, or sulfasalazine within 2 weeks prior to enrollment
- Azathioprine or cyclophosphamide within 12 weeks prior to enrollment
- Monoclonal antibodies targeting B cells (e.g., rituximab) within 12 weeks prior to enrollment
- 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)
Trial locations and contacts
24 sites in 7 countries.
24 sites in 7 countries
United States12 sites
Theravance Biopharma Investigational Site
Allentown, Pennsylvania, 18103
Theravance Biopharma Investigational Site
Bethlehem, Pennsylvania, 18015
Theravance Biopharma Investigational Site
Boston, Massachusetts, 02135
Theravance Biopharma Investigational Site
Columbus, Ohio, 43214
Theravance Biopharma Investigational Site
Denver, Colorado, 80220
Theravance Biopharma Investigational Site
Duarte, California, 91010
Theravance Biopharma Investigational Site
Fall River, Massachusetts, 02720
Theravance Biopharma Investigational Site
Glens Falls, New York, 12801
Theravance Biopharma
Hyde Park, New York, 11040
Theravance Biopharma Investigational Site
Kalispell, Montana, 59901
Theravance Biopharma Investigational Site
Sebring, Florida, 33870
Theravance Biopharma Investigational Site
Wenatchee, Washington, 98801
Brazil4 sites
Theravance Biopharma Investigational Site
Bela Vista, 01323-001
Theravance Biopharma Investigational Site
Botucatu, 18618-686
Theravance Biopharma Investigational Site
Caxias do Sul, 95070-560
Theravance Biopharma Investigational Site
São José do Rio Preto, 15090-000
Ukraine3 sites
Theravance Biopharma Investigational Site
Brovary, 07 400
Theravance Biopharma Investigational Site
Kyiv, 01 103
Theravance Biopharma Investigational Site
Kyiv, 01 601
Finland2 sites
Theravance Biopharma Investigational Site
Helsinki, 00290
Theravance Biopharma Investigational Site
Turku, 20520
United Kingdom1 site
Theravance Biopharma Investigational Site
Manchester, M23 9QZ
About this study
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
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.
Read the 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
- Being tested
- TD-0903, Placebo
- Keywords
- Acute lung injury, ALI, COVID-19, Coronavirus Disease 2019, inflammatory lung conditions, Inflammatory lung disease, ARDS, SARS-CoV-2, Pneumonia
- Medical subject headings
- Acute Lung Injury, COVID-19, Pneumonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TD-0903Drug
Study Drug to be administered by inhalation
PlaceboDrug
Placebo to be administered by inhalation
| Study group | Role | What they receive |
|---|---|---|
| Part 1: TD-0903 - MAD Dose A | Experimental | 6 out of 8 subjects per cohort will be randomized to receive TD-0903 MAD Dose A Receives: Drug: TD-0903 |
| Part 1: TD-0903 - MAD Dose B | Experimental | 6 out of 8 subjects per cohort will be randomized to receive TD-0903 MAD Dose B Receives: Drug: TD-0903 |
| Part 1: TD-0903 - MAD Dose C | Experimental | 6 out of 8 subjects per cohort will be randomized to receive TD-0903 MAD Dose C Receives: Drug: TD-0903 |
| Part 1: Placebo for MAD | Experimental | 2 out of 8 subjects per cohort (up to 3 cohorts) will be randomized to receive placebo Receives: Drug: Placebo |
| Part 2: TD-0903 | Experimental | 99 subjects will be randomized to receive TD-0903 Receives: Drug: TD-0903 |
| Part 2: Placebo | Experimental | 99 subjects will be randomized to receive Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 2: Number of Respiratory Failure-free Days (RFDs) From Randomization to Day 28
An RFD was defined as a day that a participant was alive and did not require the use of any respiratory support (invasive mechanical ventilation, non-invasive positive pressure ventilation, high-flow oxygen devices, or oxygen supplementation) from randomization through Day 28. The number of RFDs was 0 for participants who used respiratory support for 28 days or longer or for participants who died on or before Day 28.
A clinical status score of ≤ 4 on a given day was equivalent to an RFD. The clinical status categories and associated scores ranged from 1-8 where a higher score represented a worse outcome. A clinical status score of 4 was defined as a participant who was hospitalized, not requiring supplemental oxygen, but requiring ongoing medical care (whether or not related to COVID-19).
Measured: Randomization to Day 28
Secondary outcomes (3)
Part 2: Change From Baseline in SaO2/FiO2 Ratio on Day 7
SaO2/FiO2 ratio was calculated as SaO2 divided by FiO2.
Measured: Baseline and Day 7
Part 2: Number of Participants in Each Category of the 8-point Ordinal Clinical Status Scale on Days 7, 14, 21, and 28
The clinical status categories and associated scores ranged from 1-8 where a higher score represented a worse outcome. The scale was as follows:
- Score 1: Not hospitalized, no limitations on activities
- Score 2: Not hospitalized, but with limitations on activities and/or requiring home oxygen
- Score 3: Hospitalized, not requiring supplemental oxygen, and no longer requiring ongoing medical care
- Score 4: Hospitalized, not requiring supplemental oxygen, but requiring ongoing medical care (whether or not related to COVID-19)
- Score 5: Hospitalized, requiring supplemental oxygen
- Score 6: Hospitalized, on non-invasive ventilation or high-flow oxygen devices
- Score 7: Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation
- Score 8: Death
Measured: Days 7, 14, 21 and 28
Part 2: Number of Participants Alive and Respiratory Failure-free on Day 28
Defined as participants who were alive and did not require the use of any respiratory support (invasive mechanical ventilation, non-invasive positive pressure ventilation, high-flow oxygen devices, or oxygen supplementation) on Day 28.
Measured: Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 May 2020
- Study start24 Jun 2020
- Primary completion21 Apr 2021
- Study completion21 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Lung Injury (ALI) Associated With COVID-19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Parallel group, randomized, double-blind, placebo-controlled
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 235 participants (actual)
Sponsor and investigators
- Lead sponsor
- Theravance Biopharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, Study director, Theravance Biopharma
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04402866
- Sponsor's protocol ID
- 0188
- Other IDs
- 2020-001807-18
- Status last verified
- Mar 2022
- First submitted
- 22 May 2020
- Last updated
- 17 Mar 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Theravance Biopharma, Inc. will not be sharing individual de-identified participant data or other relevant study documents.
Publications
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.
PubMed 37460276
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04402866
- Acronym / sponsor ID
- 0188
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 235 participants (actual)
- Lead sponsor
- Theravance BiopharmaIndustry (pharma, biotech, devices)
- Study start
- 24 Jun 2020 (actual)
- Primary completion
- 21 Apr 2021 (actual)
- Study completion
- 21 Apr 2021 (actual)
- First posted
- 27 May 2020 (actual)
- Results
- Posted 17 Mar 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 6
- Model description
- Parallel group, randomized, double-blind, placebo-controlled
| Arm | Type | Receives |
|---|---|---|
| Part 1: TD-0903 - MAD Dose A | Experimental | Drug: TD-09036 out of 8 subjects per cohort will be randomized to receive TD-0903 MAD Dose A |
| Part 1: TD-0903 - MAD Dose B | Experimental | Drug: TD-09036 out of 8 subjects per cohort will be randomized to receive TD-0903 MAD Dose B |
| Part 1: TD-0903 - MAD Dose C | Experimental | Drug: TD-09036 out of 8 subjects per cohort will be randomized to receive TD-0903 MAD Dose C |
| Part 1: Placebo for MAD | Experimental | Drug: Placebo2 out of 8 subjects per cohort (up to 3 cohorts) will be randomized to receive placebo |
| Part 2: TD-0903 | Experimental | Drug: TD-090399 subjects will be randomized to receive TD-0903 |
| Part 2: Placebo | Experimental | Drug: Placebo99 subjects will be randomized to receive Placebo |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (23 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TD-0903Study Drug to be administered by inhalation | Drug | Part 1: TD-0903 - MAD Dose A, Part 1: TD-0903 - MAD Dose B, Part 1: TD-0903 - MAD Dose C, Part 2: TD-0903 |
| PlaceboPlacebo to be administered by inhalation | Drug | Part 1: Placebo for MAD, Part 2: Placebo |
Primary outcome
Part 2: Number of Respiratory Failure-free Days (RFDs) From Randomization to Day 28
Time frame: Randomization to Day 28
An RFD was defined as a day that a participant was alive and did not require the use of any respiratory support (invasive mechanical ventilation, non-invasive positive pressure ventilation, high-flow oxygen devices, or oxygen supplementation) from randomization through Day 28. The number of RFDs was 0 for participants who used respiratory support for 28 days or longer or for participants who died on or before Day 28. A clinical status score of ≤ 4 on a given day was equivalent to an RFD. The clinical status categories and associated scores ranged from 1-8 where a higher score represented a worse outcome. A clinical status score of 4 was defined as a participant who was hospitalized, not requiring supplemental oxygen, but requiring ongoing medical care (whether or not related to COVID-19).
3 secondary outcomes
Part 2: Change From Baseline in SaO2/FiO2 Ratio on Day 7
Time frame: Baseline and Day 7
Part 2: Number of Participants in Each Category of the 8-point Ordinal Clinical Status Scale on Days 7, 14, 21, and 28
Time frame: Days 7, 14, 21 and 28
Part 2: Number of Participants Alive and Respiratory Failure-free on Day 28
Time frame: Day 28
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37460276Belperio 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.
- Individual participant dataSharing planned: No. Theravance Biopharma, Inc. will not be sharing individual de-identified participant data or other relevant study documents.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Monitor study director
Theravance Biopharma
24 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing TD-0903 in people with Acute Lung Injury (ALI) Associated With COVID-19 and Lung Inflammation Associated With COVID-19, run by Theravance Biopharma at 24 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in United States, Brazil, Ukraine, Finland, Moldova and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Mar 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part 2: Number of Respiratory Failure-free Days (RFDs) From Randomization to Day 28 (time frame: Randomization to Day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04402866, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2022.