TD-1473 Long-Term Safety (LTS) Ulcerative Colitis (UC) Study

• ClinicalTrials.gov Identifier: NCT03920254
• Recruitment Status: Not yet recruiting
• First Posted: April 18, 2019
• Last Update Posted: March 23, 2020
• Sponsor: Theravance Biopharma
• Information provided by (Responsible Party): Theravance Biopharma

Tracking Information

• First Submitted Date: March 28, 2019
• First Posted Date: April 18, 2019
• Last Update Posted Date: March 23, 2020
• Estimated Study Start Date: March 2020
• Estimated Primary Completion Date: September 2028 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 22, 2019)

• Adverse Events [ Time Frame: Day 1 to a maximum of Week 160 (156 weeks treatment + 4 week follow-up) ]
  Incidence and severity of treatment-emergent adverse events
• Laboratory Safety tests [ Time Frame: Day 1 to a maximum of Week 160 (156 weeks treatment + 4 week follow-up) ]
  Number of subjects with laboratory test abnormalities
• ECGs [ Time Frame: Day 1 to a maximum of Week 160 (156 weeks treatment + 4 week follow-up) ]
  Number of subjects with clinically significant ECG findings
• Vital Signs [ Time Frame: Day 1 to a maximum of Week 160 (156 weeks treatment + 4 week follow-up) ]
  Number of subjects with clinically significant vital sign abnormalities

Original Primary Outcome Measures (submitted: April 15, 2019)

• Adverse Events [ Time Frame: Day 1 to a maximum of Week 160 (156 weeks treatment + 4 week follow-up) ]
  Incidence and severity of treatment-emergent adverse events
• Laboratory Safety tests: Chemistry - Sodium [ Time Frame: Day 1 to a maximum of Week 160 (156 weeks treatment + 4 week follow-up) ]
  Changes in laboratory safety tests: Chemistry - Sodium
• Laboratory Safety tests: Chemistry - Potassium [ Time Frame: Day 1 to a maximum of Week 160 (156 weeks treatment + 4 week follow-up) ]
  Changes in laboratory safety tests: Chemistry - Potassium
• Laboratory Safety tests: Chemistry - Calcium [ Time Frame: Day 1 to a maximum of Week 160 (156 weeks treatment + 4 week follow-up) ]
  Changes in laboratory safety tests: Chemistry - Calcium
• Laboratory Safety tests: Chemistry - Magnesium [ Time Frame: Day 1 to a maximum of Week 160 (156 weeks treatment + 4 week follow-up) ]
  Changes in laboratory safety tests: Chemistry - Magnesium
• Laboratory Safety tests: Hematology - Hematocrit [ Time Frame: Day 1 to a maximum of Week 160 (156 weeks treatment + 4 week follow-up) ]
  Changes in laboratory safety tests: Hematology - Hematocrit
• Laboratory Safety tests: Hematology - Hemoglobin [ Time Frame: Day 1 to a maximum of Week 160 (156 weeks treatment + 4 week follow-up) ]
  Changes in laboratory safety tests: Hematology - Hemoglobin
• Laboratory Safety tests: Hematology - White Blood Cell Count [ Time Frame: Day 1 to a maximum of Week 160 (156 weeks treatment + 4 week follow-up) ]
  Changes in laboratory safety tests: Hematology - White Blood Cell Count
• Laboratory Safety tests: Hematology - Eosinophils [ Time Frame: Day 1 to a maximum of Week 160 (156 weeks treatment + 4 week follow-up) ]
  Changes in laboratory safety tests: Hematology - Eosinophils
• ECGs: QT Interval [ Time Frame: Day 1 to a maximum of Week 160 (156 weeks treatment + 4 week follow-up) ]
  Changes in ECG: QT Interval
• Vital Signs: Heart Rate [ Time Frame: Day 1 to a maximum of Week 160 (156 weeks treatment + 4 week follow-up) ]
  Changes in Heart Rate
• Vital Signs: Blood Pressure [ Time Frame: Day 1 to a maximum of Week 160 (156 weeks treatment + 4 week follow-up) ]
  Changes in Blood Pressure
• Vital Signs: Temperature [ Time Frame: Day 1 to a maximum of Week 160 (156 weeks treatment + 4 week follow-up) ]
  Changes in Temperature
• Vital Signs: Respirations [ Time Frame: Day 1 to a maximum of Week 160 (156 weeks treatment + 4 week follow-up) ]
  Changes in Respirations

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: TD-1473 Long-Term Safety (LTS) Ulcerative Colitis (UC) Study
• Official 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)
• Brief Summary: A 3-Year Multi-Center, Long-Term Safety (LTS) Study to Evaluate the Safety and Tolerability of TD−1473 in Subjects with Ulcerative Colitis who have participated in the Maintenance Study of Protocol 0157
• Detailed Description: This is a multi-center, long-term safety study to evaluate the safety and tolerability of TD-1473 for up to 156 weeks (3 years) + 4 week follow-up in subjects with moderate to severe UC exiting the preceding Maintenance Study of Protocol 0157 (NCT03758443).
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3

Study Design

Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Long Term Safety (LTS)

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

• Condition: Ulcerative Colitis (UC)

Intervention

• Drug: TD-1473 Dose A
  See Arm description
• Drug: TD-1473 Dose B
  See Arm description
• Drug: TD-1473 Dose C
  See Arm description

Study Arms

• Experimental: Active Treatment TD-1473 with Dose A
  Oral daily dose of TD-1473 for up to 156 weeks
  Intervention: Drug: TD-1473 Dose A
• Experimental: Active Treatment TD-1473 with Dose B
  Oral daily dose of TD-1473 for up to 156 weeks
  Intervention: Drug: TD-1473 Dose B
• Experimental: Active Treatment TD-1473 with Dose C
  Oral daily dose of TD-1473 for up to 156 weeks
  Intervention: Drug: TD-1473 Dose C

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: April 15, 2019): 500
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 2028
• Estimated Primary Completion Date: September 2028 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

To be eligible for the study, subjects are required to enter the LTS Study within 14 days of exiting the Maintenance Study of Protocol 0157 and must meet all the following criteria:

• Capable of providing informed consent, which must be obtained prior to any study related procedures.

• One of the following:

  • Those who demonstrated persistent loss of response (no improvement 8 weeks after meeting loss of response criteria) OR
  • Two Clinical Flares after an episode of loss of response during the Maintenance Study OR
  • Those who have completed the Maintenance Study and confirmation of clinical remission status results are available
• 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
• All male subjects must agree to refrain from semen donation during the study and for 7 days after the last dose of study drug.
• Must be able and willing to adhere to the study visit schedule and comply with other study requirements.

Exclusion Criteria:

• Has symptoms suggestive of fulminant colitis, megacolon or intestinal perforation
• Likely to require surgery for UC or other major surgeries
• Has previously received / is currently receiving prohibited medications
• Has been diagnosed during Protocol 0157 with Crohn's disease, other colitis conditions or the subject has a current or past diagnosis of a fistula or abdominal abscess
• Has endoscopic findings during Protocol 0157 of colitis-associated colonic dysplasia (with the exception of subjects with non-colitis associated spontaneous adenomas that have been completely resected)
• Has clinically significant abnormalities in laboratory evaluations
• Additional exclusion criteria apply

Sex/Gender

• Sexes Eligible for Study: All
• Gender Based Eligibility: Yes

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Theravance Biopharma Call Center; 1-855-633-8479; medinfo@theravance.com

• Listed Location Countries: Bulgaria, Georgia, Greece, Hungary, Israel, Japan, Poland, Portugal, Serbia, Slovakia, South Africa, Spain, Taiwan, Ukraine, United States

Administrative Information

• NCT Number: NCT03920254
• Other Study ID Numbers: 0164; 2018-002135-19 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: Theravance Biopharma, Inc. will not be sharing individual de-identified participant data or other relevant study documents.

• Responsible Party: Theravance Biopharma
• Study Sponsor: Theravance Biopharma
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Theravance Biopharma

• PRS Account: Theravance Biopharma
• Verification Date: March 2020