Ulcerative Colitis (UC)
Conditions
Keywords
TD-1473, Janus kinase inhibitor, JAK inhibitor, Inflammatory Bowel Disease, IBD, Ulcerative colitis, UC, Intestinal restriction, Gut-selective
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).
Interventions
DRUGTD-1473 Dose A
See Arm description
DRUGTD-1473 Dose B
See Arm description
DRUGTD-1473 Dose C
See Arm description
Sponsors
Theravance Biopharma
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Long Term Safety (LTS)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | Day 1 up to 4 weeks after last dose of study drug (median treatment duration was: TD-1473 20 mg - 142 days; TD-1473 80 mg - 180.0 days; TD-1473 200 mg - 158 days) | A TEAE was defined as any AE with a recorded start date on or after the date of the first dose of study drug up through 4 weeks after the last dose of study drug. Any clinically significant changes in laboratory safety tests, electrocardiograms (ECGs) and vital signs, were also recorded as TEAEs. |
Countries
Australia, Bulgaria, Canada, France, Georgia, Germany, Greece, Hungary, Israel, Italy, Japan, Poland, Portugal, Romania, Serbia, Slovakia, South Africa, South Korea, Spain, Taiwan, Ukraine, United States
Participant flow
Recruitment details
46 out of the planned 500 participants were enrolled and received study drug between 23 July 2020 and 27 October 2021.
Participants by arm
| Arm | Count |
|---|---|
| TD-1473 20mg Participants received TD-1473 orally at a dose of 20mg once daily. | 13 |
| TD-1473 80mg Participants received TD-1473 orally at a dose of 80mg once daily. | 18 |
| TD-1473 200mg Participants received TD-1473 orally at a dose of 200mg once daily. | 15 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 1 | 2 |
| Overall Study | Study Terminated By Sponsor | 12 | 17 | 12 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | TD-1473 20mg | TD-1473 80mg | TD-1473 200mg | Total |
|---|---|---|---|---|
| Age, Continuous | 46.31 years STANDARD_DEVIATION 17.375 | 43.22 years STANDARD_DEVIATION 15.869 | 46.13 years STANDARD_DEVIATION 13.432 | 45.04 years STANDARD_DEVIATION 15.296 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 17 Participants | 15 Participants | 44 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 12 Participants | 15 Participants | 13 Participants | 40 Participants |
| Sex: Female, Male Female | 8 Participants | 7 Participants | 7 Participants | 22 Participants |
| Sex: Female, Male Male | 5 Participants | 11 Participants | 8 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 18 | 0 / 15 |
| other Total, other adverse events | 4 / 13 | 5 / 18 | 5 / 15 |
| serious Total, serious adverse events | 0 / 13 | 0 / 18 | 1 / 15 |
Outcome results
Primary
Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)
A TEAE was defined as any AE with a recorded start date on or after the date of the first dose of study drug up through 4 weeks after the last dose of study drug. Any clinically significant changes in laboratory safety tests, electrocardiograms (ECGs) and vital signs, were also recorded as TEAEs.
Time frame: Day 1 up to 4 weeks after last dose of study drug (median treatment duration was: TD-1473 20 mg - 142 days; TD-1473 80 mg - 180.0 days; TD-1473 200 mg - 158 days)
Population: Includes all participants from the Safety Analysis Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TD-1473 20mg | Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | 4 Participants |
| TD-1473 80mg | Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | 5 Participants |
| TD-1473 200mg | Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | 6 Participants |