Clinical Trials Register

Summary
EudraCT Number:	2020-001807-18
Sponsor's Protocol Code Number:	TD-0903-0188
National Competent Authority:	Finland - Fimea
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-07-29
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Finland - Fimea

A.2

EudraCT number

2020-001807-18

A.3

Full title of the trial

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

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

TD-0903 for ALI Associated with COVID-19

A.3.2

Name or abbreviated title of the trial where available

TD-0903 for ALI Associated with COVID-19

A.4.1

Sponsor's protocol code number

TD-0903-0188

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT04402866

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Theravance Biopharma Ireland Limited
B.1.3.4	Country	Ireland
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Theravance Biopharma Ireland Limited
B.4.2	Country	Ireland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Theravance Biopharma Ireland Limited
B.5.2	Functional name of contact point	Rajeev Saggar
B.5.3	Address:
B.5.3.1	Street Address	901 Gateway Blvd
B.5.3.2	Town/ city	San Francisco
B.5.3.3	Post code	CA 94080
B.5.3.4	Country	United States
B.5.4	Telephone number	+19499221158
B.5.6	E-mail	rsaggar@theravance.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	TD-0903
D.3.4	Pharmaceutical form	Inhalation solution
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	TD-0903
D.3.9.2	Current sponsor code	TD-0903
D.3.9.3	Other descriptive name	TD-0903
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	TD-0903
D.3.4	Pharmaceutical form	Inhalation solution
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	TD-0903
D.3.9.2	Current sponsor code	TD-0903
D.3.9.3	Other descriptive name	TD-0903
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	3
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	TD-0903
D.3.4	Pharmaceutical form	Inhalation solution
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	TD-0903
D.3.9.2	Current sponsor code	TD-0903
D.3.9.3	Other descriptive name	TD-0903
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Inhalation solution
D.8.4	Route of administration of the placebo	Inhalation use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Acute lung injury associated with COVID-19

E.1.1.1

Medical condition in easily understood language

Lung injury

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	HLT
E.1.2	Classification code	10047468
E.1.2	Term	Viral lower respiratory tract infections
E.1.2	System Organ Class	100000004855

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Part 1
• Evaluate the safety and tolerability of inhaled TD-0903 in subjects with COVID 19;
• Assess the plasma pharmacokinetics (PK) of TD-0903 in subjects with COVID 19;
• Characterize the effect of TD-0903 on reducing the acute lung injury (as measured by SaO2/FiO2 ratio) associated with COVID-19;
• Explore the effect of TD-0903 on swab viral infection status, SARSCoV-2 antibody levels, blood cytokine levels and biomarkers of inflammation, thrombosis and lung injury.

Part 2
• To characterize the efficacy of TD-0903 as measured by respiratory failure-free days (RFDs).

E.2.2

Secondary objectives of the trial

• Reducing the acute lung injury (as measured by SaO2/FiO2 ratio) associated with COVID-19;
• Safety and tolerability;
• Clinical outcomes as measured by an 8-point clinical status scale;
• The proportion of subjects alive and respiratory failure-free.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Willing and able to provide written informed consent on their own prior to performing study procedures.
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 collected 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 < 14 days prior to hospital admission.

E.4

Principal 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 infections 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.
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:
• New York Heart Association class IV Heart Failure
• Hepatic dysfunction (i.e., AST or ALT >3x upper limit of normal)
• Renal dysfunction (i.e., estimated glomerular filtration rate (eGFR) <50 mL/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/μL), lymphopenia (i.e., absolute lymphocyte count < 200 cells/μL) or thrombocytopenia (i.e., platelets < 50×109/L).
• Hypersensitivity to TD-0903 or its components, or to other JAK inhibitors.
• Treatment with anti-IL 6 (eg tocilizumab, sarilumab), anti-IL-1, anti-T cell (e.g., abatacept) antibodies, anti-IL-6R antagonists, or with JAK inhibitors in the past 30 days, or plans to receive a JAK inhibitor (e.g., baricitinib, tofacitinib), supplemental interferon therapy, or tyrosine kinase inhibitors (e.g.,umatibib, genfinitib) 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 (eg 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 related to COVID-19, except in the context of a single-arm antiviral 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 cardiorespiratory history in the past 90 days.
• Body Mass Index ≥40 kg/cm2.
• Receipt of any 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).

E.5 End points

E.5.1

Primary end point(s)

Part 1
• Change in vital signs and clinical laboratory results;
• Incidence and severity of treatment-emergent AEs
• Plasma PK parameters;
• Change in SaO2/FiO2 ratio.

Part 2
• Number of RFDs.

E.5.1.1

Timepoint(s) of evaluation of this end point

Part 1
• Change in vital signs and clinical laboratory results: Day 1 to Day 28;
• Incidence and severity of treatment-emergent AEs: Day o to Day 28;
• Plasma PK parameters: Day 1 – Pre-dose, + 15 min, + 30 min, + 1 h, + 2 h, + 4 h, + 6 h, + 8 h, + 12 h, +24 h
Day 7 - – Pre-dose, + 15 min, + 30 min, + 1 h, + 2 h, + 4 h, + 6 h, + 8 h, + 12 h, +24 h;
• Change in SaO2/FiO2 ratio: Day 1 to Day 7.

Part 2
• Number of RFDs: Day 1 to Day 28.

E.5.2

Secondary end point(s)

Part1:
N/A

Part2:
• Change in SaO2/fiO2 ratio
• Proportion of subjects in each category of the 8-point clinical status scale;
• Proportion of subjects alive and respiratory-failure free.

E.5.2.1

Timepoint(s) of evaluation of this end point

• Change in SaO2/fiO2 ratio: Day 7;
• Proportion of subjects in each category of the 8-point clinical status
Scale: Day 7, Day 14, Day 21, and Day 28;
• Proportion of subjects alive and respiratory-failure free: Day28.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Argentina

Brazil

Finland

Moldova, Republic of

Poland

Romania

South Africa

Ukraine

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

150

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

222

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2020-08-11

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-10-13

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-04-21

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