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

• Register: EUCTR
• Last refreshed on: 8 October 2021
• Main ID: EUCTR2018-002135-19-HU
• Date of registration: 19/02/2019
• Prospective Registration: Yes
• Primary sponsor: Theravance Biopharma Ireland Limited
• Public title: A clinical trial to investigate the Efficacy and Safety of TD-1473 for the Treatment of Ulcerative Colitis (UC)
• Scientific title: 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) - TD-1473 LTS UC Study
• Date of first enrolment: 11/04/2019
• Target sample size: 500
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-002135-19
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Bulgaria, Canada, Croatia, France, Georgia, Germany, Greece, Hungary, Israel, Italy, Poland, Portugal, Russian Federation, Serbia, Slovakia, South Africa, Spain, Taiwan, Ukraine, United Kingdom, United States

Contacts

• Name: Clinical Operations - CC
• Affiliation: Theravance Biopharma Ireland Limited

• Name: Clinical Operations - CC
• Affiliation: Theravance Biopharma Ireland Limited

Key inclusion & exclusion criteria

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.
Are the trial subjects under 18? no
Number of subjects for this age range:
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 50

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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Moderately-to-severely active Ulcerative Colitis (UC)
MedDRA version: 20.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Intervention(s)

Product Name: TD-1473
Product Code: TD-1473
Pharmaceutical Form: Coated tablet
INN or Proposed INN: Not assigned
Current Sponsor code: TD-1473
Other descriptive name: THRX-139060
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Product Name: TD-1473
Product Code: TD-1473
Pharmaceutical Form: Coated tablet
INN or Proposed INN: Not assigned
Current Sponsor code: TD-1473
Other descriptive name: THRX-139060
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-

Product Name: TD-1473
Product Code: TD-1473
Pharmaceutical Form: Coated tablet
INN or Proposed INN: Not assigned
Current Sponsor code: TD-1473
Other descriptive name: THRX-139060
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Primary end point(s): Incidence and severity of treatment-emergent adverse events, changes in laboratory safety tests, ECGs, and vital sign measurements.

Timepoint(s) of evaluation of this end point: throughout study duration

Main Objective: 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.

Secondary Objective: • 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)

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 12 and at scheduled time points throughout study duration

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

Secondary ID(s)

0164

128299

Source(s) of Monetary Support

Theravance Biopharma Ireland Limited

Ethics review

Status: Approved
Approval date: 09/04/2019
Contact: