Efficacy & Safety of TD-1473 in Ulcerative Colitis (RHEA)
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| ClinicalTrials.gov Identifier: NCT03758443 |
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Recruitment Status :
Terminated
(Stopped early due to company decision. Company decision based on interim analysis results in TD-1473-0157.)
First Posted : November 29, 2018
Results First Posted : November 15, 2022
Last Update Posted : November 15, 2022
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Ulcerative Colitis (UC) | Drug: TD-1473 Dose A Drug: TD-1473 Dose B Drug: TD-1473 Dose C Drug: Placebo | Phase 2 Phase 3 |
This protocol consists of 3 separate studies: an 8-week Phase 2b dose-finding induction study, an 8-week dose-confirming Phase 3 induction study, and a 44-week Phase 3 maintenance study. Subjects who respond to induction will enter the maintenance study; those who do not will receive TD-1473 during extended induction. The safety and efficacy data of the Phase 2b study will be analyzed to select the induction and maintenance dose regimens for the confirmatory Phase 3 studies. Participants who have disease relapse or complete the maintenance study may be eligible to enter a separate long-term safety study. Efficacy, pharmacokinetic, biomarkers, and safety will be evaluated in all 3 studies.
240 subjects are planned for the Phase 2b and the planned Primary Completion Date for this portion of the study is JULY 2021. 640 subjects are planned for the Phase 3 portion of the study.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 239 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | Integrated and Adaptive Design |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 2b/3 Multi-Center, Randomized, Double-Blind, Multi-Dose, Placebo-Controlled, Parallel-Group Set of Studies to Evaluate the Efficacy and Safety of Induction and Maintenance Therapy With TD-1473 in Subjects With Moderately-to-Severely Active Ulcerative Colitis |
| Actual Study Start Date : | March 11, 2019 |
| Actual Primary Completion Date : | October 20, 2021 |
| Actual Study Completion Date : | October 20, 2021 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Active Treatment TD-1473 Dose A
Participants will be randomized to receive an oral daily dose of TD-1473. Responders will be re-randomized into the Phase 3 Maintenance portion of the study. Non-responders may participate in an extended induction.
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Drug: TD-1473 Dose A
See Arm description |
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Experimental: Active Treatment TD-1473 Dose B
Participants will be randomized to receive an oral daily dose of TD-1473. Responders will be re-randomized into the Phase 3 Maintenance portion of the study. Non-responders may participate in an extended induction.
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Drug: TD-1473 Dose B
See Arm description |
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Experimental: Active Treatment TD-1473 Dose C
Participants will be randomized to receive an oral daily dose of TD-1473. Responders will be re-randomized into the Phase 3 Maintenance portion of the study. Non-responders may participate in an extended induction.
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Drug: TD-1473 Dose C
See Arm description |
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Placebo Comparator: Placebo
Participants will be randomized to receive an oral daily dose of placebo. Participants who received Placebo (and were non-responders) may move to an extended induction. Subjects who are on placebo will be assigned to active TD-1473 for the extended induction (they will be blinded to dose).
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Drug: Placebo
See Arm description |
- Change From Baseline in Total Mayo Score (tMS) at Week 8 [ Time Frame: Baseline to Week 8 ]Total Mayo Score (tMS) was calculated as the sum of four components: rectal bleeding (0-3), stool frequency (0-3), physician's global assessment (0-3) and Mayo endoscopic subscore (0-3). tMS was reported as a 0-12 point score with 12 reflecting the highest severity.
- Phase 3 Maintenance: Number of Participants Who Demonstrated Clinical Remission by Adapted Mayo Score Components at Maintenance Week (mWeek) 44 [ Time Frame: mWeek 44 ]
Clinical remission by Adapted Mayo score was defined based on Adapted Mayo score components within specific ranges: stool frequency score of 0 or 1, a rectal bleeding subscore of 0 and a Mayo endoscopy subscore of 0 or 1.
The Adapted Mayo score was the sum of three components: rectal bleeding, stool frequency, and Mayo endoscopic subscore, each measured on a scale of 0-3 with higher scores reflecting higher severity.
Participants with missing Week 44 values were imputed as non-responders.
- Number of Participants Who Demonstrated Clinical Remission by Adapted Mayo Score Components at Week 8 [ Time Frame: Week 8 ]
Clinical remission by Adapted Mayo score was defined based on Adapted Mayo score components within specific ranges: stool frequency score of 0 or 1, a rectal bleeding subscore of 0 and a Mayo endoscopy subscore of 0 or 1.
The Adapted Mayo score was the sum of three components: rectal bleeding, stool frequency, and Mayo endoscopic subscore, each measured on a scale of 0-3 with higher scores reflecting higher severity.
- Phase 3 Maintenance: Number of Participants Who Demonstrated a Clinical Response by Adapted Mayo Score Components at mWeek 44 [ Time Frame: Baseline to mWeek 44 ]
Clinical response was defined as a reduction from baseline in adapted Mayo score of ≥ 2 points and ≥ 30% relative to baseline. It also required ≥ 1 reduction in the rectal bleeding subscore or an absolute subscore ≤ 1.
The Adapted Mayo score was the sum of three components: rectal bleeding, stool frequency, and Mayo endoscopic subscore, each measured on a scale of 0-3 with higher scores reflecting higher severity.
Participants with missing Week 44 values were imputed as non-responders.
- Phase 3 Maintenance: Number of Participants Who Demonstrated Endoscopic Remission by Adapted Mayo Score Components at mWeek 44 [ Time Frame: mWeek 44 ]
Endoscopic remission was defined as an endoscopic subscore ≤ 1.
Endoscopic subscore was measured using scale of 0-3, where higher numbers reflected greater severity.
- Phase 3 Maintenance: Number of Participants Who Demonstrated Symptomatic Remission by Adapted Mayo Score Components at mWeek 44 [ Time Frame: mWeek 44 ]
Symptomatic remission was defined as a stool frequency score ≤ 1 and a rectal bleeding subscore of 0.
Stool frequency score and rectal bleeding score were each measured using scale of 0-3, where higher numbers reflected greater severity.
Participants with missing Week 44 values were imputed as non-responders.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Gender Based Eligibility: | Yes |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Is at least 18 years of age at screening
- Has a history of UC for at least 3 months prior to screening
- Has moderately-to-severely active UC, as defined by a Mayo endoscopic subscore of ≥2 points and an adapted Mayo score between 4 - 9 points inclusive
- Is corticosteroid-dependent or has demonstrated inadequate response, or intolerance to conventional therapy (aminosalicylates, corticosteroids, immunomodulators) or biologics
- Willing to use highly-effective methods of contraception during the study and for 7 days after the last dose
- Additional inclusion criteria apply
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 within specified timeframe
- Is refractory to 3 biologics with ≥2 mechanisms of action
- Has a current bacterial, parasitic, fungal, or viral infection
- Has clinically significant abnormalities in laboratory evaluations
- Has had any prior exposure to an approved Janus kinase (JAK) inhibitor or potential exposure to an investigational JAK inhibitor that was stopped due to intolerance or lack of efficacy
- Additional exclusion criteria apply
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03758443
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| Study Director: | Medical Monitor | Theravance Biopharma |
Documents provided by Theravance Biopharma:
| Responsible Party: | Theravance Biopharma |
| ClinicalTrials.gov Identifier: | NCT03758443 |
| Other Study ID Numbers: |
0157 2018-002136-24 ( EudraCT Number ) |
| First Posted: | November 29, 2018 Key Record Dates |
| Results First Posted: | November 15, 2022 |
| Last Update Posted: | November 15, 2022 |
| Last Verified: | November 2021 |
| Individual Participant Data (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. |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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TD-1473 Janus kinase inhibitor JAK inhibitor Inflammatory Bowel Disease |
IBD Ulcerative colitis UC Gut selective |
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Colitis Colitis, Ulcerative Ulcer Gastroenteritis Gastrointestinal Diseases |
Digestive System Diseases Colonic Diseases Intestinal Diseases Pathologic Processes Inflammatory Bowel Diseases |