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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

235

participants targeted

Target at P75+ for phase_2

Timeline

Completed

Started Jun 2020

Shorter than P25 for phase_2

Geographic Reach

7 countries

24 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

10 months study duration

First Submitted

Initial submission to the registry

May 22, 2020

Completed

5 days until next milestone

First Posted

Study publicly available on registry

May 27, 2020

Completed

28 days until next milestone

Study Start

First participant enrolled

June 24, 2020

Completed

10 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 21, 2021

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 21, 2021

Completed

11 months until next milestone

Results Posted

Study results publicly available

March 17, 2022

Completed

Last Updated

March 17, 2022

Status Verified

March 1, 2022

Enrollment Period

10 months

First QC Date

May 22, 2020

Results QC Date

February 25, 2022

Last Update Submit

March 15, 2022

Conditions

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

Keywords

Acute lung injuryALICOVID-19Coronavirus Disease 2019inflammatory lung conditionsInflammatory lung diseaseARDSSARS-CoV-2Pneumonia

Outcome Measures

Primary Outcomes (1)

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).
Randomization to Day 28

Secondary Outcomes (3)

Part 2: Change From Baseline in SaO2/FiO2 Ratio on Day 7
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
Days 7, 14, 21 and 28
Part 2: Number of Participants Alive and Respiratory Failure-free on Day 28
Day 28

Study Arms (6)

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

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

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

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

Drug: Placebo

Part 2: TD-0903

EXPERIMENTAL

99 subjects will be randomized to receive TD-0903

Drug: TD-0903

Part 2: Placebo

EXPERIMENTAL

99 subjects will be randomized to receive Placebo

Drug: Placebo

Interventions

TD-0903DRUG

Study Drug to be administered by inhalation

Part 1: TD-0903 - MAD Dose APart 1: TD-0903 - MAD Dose BPart 1: TD-0903 - MAD Dose CPart 2: TD-0903

PlaceboDRUG

Placebo to be administered by inhalation

Part 1: Placebo for MADPart 2: Placebo

Eligibility Criteria

Age18 Years - 80 Years

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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:
Methotrexate, cyclosporine, mycophenolate, tacrolimus, penicillamine, or sulfasalazine within 2 weeks prior to enrollment
Azathioprine or cyclophosphamide within 12 weeks prior to enrollment
+8 more criteria

Contact the study team to confirm eligibility.