Efficacy & Safety of TD-1473 in Ulcerative Colitis (RHEA)

Theravance Biopharma

Status and phase: Terminated; Phase 3; Phase 2

Conditions: Ulcerative Colitis (UC)

Treatments: Drug: TD-1473 Dose B; Drug: TD-1473 Dose A; Drug: TD-1473 Dose C; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03758443

2018-002136-24 (EudraCT Number)

0157

Details and patient eligibility

About

A Phase 2b/3 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 with up to 60 weeks of treatment.

Full description

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.

Enrollment: 239 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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239 participants in 4 patient groups, including a placebo group

Active Treatment TD-1473 Dose A

Experimental group

Description:

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.

Treatment:

Drug: TD-1473 Dose A

Active Treatment TD-1473 Dose B

Experimental group

Description:

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.

Treatment:

Drug: TD-1473 Dose B

Active Treatment TD-1473 Dose C

Experimental group

Description:

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.

Treatment:

Drug: TD-1473 Dose C

Placebo

Placebo Comparator group

Description:

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).

Treatment:

Drug: Placebo