Clinical Trials Register

Summary
EudraCT Number:	2018-002135-19
Sponsor's Protocol Code Number:	0164
National Competent Authority:	Greece - EOF
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2019-06-04
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

Greece - EOF

A.2

EudraCT number

2018-002135-19

A.3

Full title of the trial

A 3-Year, Multi-Center, Long-Term Safety (LTS) Study to Evaluate the Safety and Tolerability of TD-1473 in Subjects with Ulcerative Colitis (UC)

A.3.1

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

A clinical trial to investigate the Efficacy and Safety of TD-1473 for the Treatment of Ulcerative Colitis (UC)

A.3.2

Name or abbreviated title of the trial where available

TD-1473 LTS UC Study

A.4.1

Sponsor's protocol code number

0164

A.5.4

Other Identifiers

Name:

US IND

Number:

128299

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	Clinical Operations - CC
B.5.3	Address:
B.5.3.1	Street Address	Connaught House 1 Burlington Road
B.5.3.2	Town/ city	Dublin 4
B.5.3.3	Post code	D04 C5Y6
B.5.3.4	Country	Ireland
B.5.4	Telephone number	35315532500
B.5.5	Fax number	35315532501
B.5.6	E-mail	IBDstudies@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-1473
D.3.2	Product code	TD-1473
D.3.4	Pharmaceutical form	Coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not assigned
D.3.9.2	Current sponsor code	TD-1473
D.3.9.3	Other descriptive name	THRX-139060
D.3.9.4	EV Substance Code	SUB192730
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
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.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-1473
D.3.2	Product code	TD-1473
D.3.4	Pharmaceutical form	Coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not assigned
D.3.9.2	Current sponsor code	TD-1473
D.3.9.3	Other descriptive name	THRX-139060
D.3.9.4	EV Substance Code	SUB192730
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	40
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-1473
D.3.2	Product code	TD-1473
D.3.4	Pharmaceutical form	Coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not assigned
D.3.9.2	Current sponsor code	TD-1473
D.3.9.3	Other descriptive name	THRX-139060
D.3.9.4	EV Substance Code	SUB192730
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Moderately-to-severely active Ulcerative Colitis (UC)

E.1.1.1

Medical condition in easily understood language

Ulcerative Colitis (UC)

E.1.1.2

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10045365
E.1.2	Term	Ulcerative colitis
E.1.2	System Organ Class	100000004856

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess the safety and tolerability of TD-1473 administered up to 3 years in subjects with moderate to severe UC after participation in the Maintenance Study of Protocol 0157.

E.2.2

Secondary objectives of the trial

• To assess clinical remission and response rates over time
• To assess endoscopic healing rates over time
• To assess clinical remission and response in subjects entering the study after experiencing persistent loss of response or recurrent clinical flare after initial loss of response during the Maintenance Study (Protocol 0157)
• To assess clinical remission and response in subjects entering the study after completing the Maintenance Study (Protocol 0157)
• To determine the effect of long-term TD-1473 treatment on major inflammatory bowel disease (IBD)-related events (eg, hospitalizations, surgeries, and procedures)
• To examine the effect of long-term TD-1473 treatment on health-related quality of life (QOL)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Capable of providing informed consent, which must be obtained prior to any study-related procedures.
2. One of the following:
a. Those who demonstrated persistent loss of response (no improvement 8 weeks after meeting loss of response criteria) or
b. two Clinical Flares after an episode of loss of response during the Maintenance Study. Loss of response must be documented by sigmoidoscopy/colonoscopy for the subject to be eligible. Subjects who declined the Clinical Flare Assessment #2 or endoscopic examination at the first Clinical Flare Assessment of Maintenance Study 0157 will not be eligible,
OR
c. Those who have completed the Maintenance Study and confirmation of clinical remission status results are available
3. During the study and for 7 days after receiving the last dose of the study drug, females of childbearing potential or men capable of fathering children must agree to use highly effective birth control measures (failure rate <1% when used consistently and correctly) or agree to abstain from sexual intercourse. Females of childbearing potential must test negative for pregnancy at Day 1.
4. All male subjects must agree to refrain from semen donation during the study and for 7 days after the last dose of study drug.
5. Must be able and willing to adhere to the study visit schedule and comply with other study requirements.

E.4

Principal exclusion criteria

1. Has current symptoms or signs suggestive of fulminant colitis, toxic megacolon, intestinal perforation
2. Has a high risk of requiring surgery for UC or any other type of major surgery (eg, requiring general anesthesia) during the study
3. Has been diagnosed during Protocol 0157 with Crohn’s disease, microscopic colitis, ischemic colitis, radiation colitis, diverticular disease associated with colitis, indeterminate colitis, or the subject has a current or past diagnosis of a fistula or abdominal abscess
4. Has endoscopic findings during Protocol 0157 of colitis-associated colonic dysplasia; however, subjects with spontaneous (non-colitis-associated) adenomas that have been completely resected are eligible
5. Taking any prohibited medications of exclusion as listed in the protocol currently or previously during Protocol 0157 Maintenance
6. Deemed by the investigator to be inappropriate for this study; or has any condition which would confound or interfere with the evaluation of the safety or tolerability of the study drug (eg, developed unstable or uncontrolled and clinically significant condition/disease during Protocol 0157); or is unable or unwilling to comply with the study protocol
7. Develops hypersensitivity to excipients or contents of the study drug as noted in Protocol 0157.
8. Participating in or interested in participating in another investigational study (exception Protocol 0157)
9. Has clinically significant abnormalities in the results of laboratory evaluations at the most recent laboratory evaluation prior to LTS Day 1 visit as determined by the investigator, including:
• AST, ALT, or alkaline phosphatase ≥ 2x the upper limit of normal (ULN)
• Total bilirubin > 2x ULN (unless diagnosis of Gilbert’s syndrome)
• Creatinine clearance as calculated by the Cockcroft-Gault formula < 30 mL/min
• Total white blood cell count (WBC) < 3 x 10^9/L
• Absolute neutrophil count < 1.5 x 10^9/L
• Absolute lymphocyte count < 0.8 x 10^9/L
• Hemoglobin < 8 g/dL
• Platelet count < 100 x 10^9/L.

E.5 End points

E.5.1

Primary end point(s)

Incidence and severity of treatment-emergent adverse events, changes in laboratory safety tests, ECGs, and vital sign measurements.

E.5.1.1

Timepoint(s) of evaluation of this end point

throughout study duration

E.5.2

Secondary end point(s)

• Proportion of subjects who achieve clinical remission by various definitions at Week 12 among subjects entering the LTS study from Protocol 0157 Maintenance Study with persistent loss of response or recurrent clinical flare after loss of response
• Proportion of subjects who achieve clinical response by various definitions at Week 12 among subjects entering the LTS study from Protocol 0157 Maintenance Study with persistent loss of response or recurrent clinical flare after loss of response
• Time to major IBD-related events (hospitalizations, surgeries, or procedures)
• Changes from baseline in IBDQ, WPAI-UC, and EuroQual (EQ-5D) scores
• Proportions of subjects achieving clinical remission as defined by various definitions at scheduled time points.
• Proportions of subjects maintaining clinical response at scheduled time points by various definitions in subjects who entered the LTS study in clinical response from the Maintenance Study in Protocol 0157
• Proportion of subjects who enter study in clinical remission and maintain clinical remission by various definitions at scheduled time points
• Proportion of subjects who enter the study in clinical response and maintain clinical response by various definitions at scheduled time points
• Changes from baseline in partial, adapted, and total Mayo scores at scheduled time points (both Protocol 0157 Induction and Protocol 0157 Maintenance baseline)
• Proportion of subjects achieving endoscopic response at scheduled time points
• Proportion of subjects achieving endoscopic remission at scheduled time points

E.5.2.1

Timepoint(s) of evaluation of this end point

Week 12 and at scheduled time points throughout study duration

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

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

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

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

Australia

Bulgaria

Canada

Croatia

France

Georgia

Germany

Greece

Hungary

Israel

Poland

Portugal

Russian Federation

Serbia

Slovakia

South Africa

Spain

Taiwan

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 years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

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:

450

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

200

F.4.2.2

In the whole clinical trial

500

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)

Standard of Care

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

2019-07-30

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-09-13

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2021-09-01

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