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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03758443




Registration number
NCT03758443
Ethics application status
Date submitted
19/11/2018
Date registered
29/11/2018
Date last updated
19/10/2020

Titles & IDs
Public title
Efficacy & Safety of TD-1473 in Ulcerative Colitis
Scientific 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
Secondary ID [1] 0 0
0157
Universal Trial Number (UTN)
Trial acronym
RHEA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ulcerative Colitis (UC) 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Oral and Gastrointestinal 0 0 0 0
Inflammatory bowel disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - TD-1473 Dose A
Treatment: Drugs - TD-1473 Dose B
Treatment: Drugs - TD-1473 Dose C
Treatment: Drugs - Placebo

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.

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.

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.

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).


Treatment: Drugs: TD-1473 Dose A
See Arm description

Treatment: Drugs: TD-1473 Dose B
See Arm description

Treatment: Drugs: TD-1473 Dose C
See Arm description

Treatment: Drugs: Placebo
See Arm description

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 2b Induction: Change from baseline in total Mayo score (tMS) at Week 8 - Total Mayo Score (tMS) is 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 is reported as a 0-12 point score with 12 reflecting the highest severity.
Timepoint [1] 0 0
Baseline to Week 8
Primary outcome [2] 0 0
Phase 3 Induction: Clinical remission by adapted Mayo score components at Week 8 - Clinical remission by Adapted Mayo score is 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 is the sum of three components: rectal bleeding, stool frequency, and Mayo endoscopic subscore, each measured on a scale of 0-3.
Timepoint [2] 0 0
Week 8
Primary outcome [3] 0 0
Phase 3 Maintenance: Clinical remission by adapted Mayo score components at Maintenance (m) Week 44 - Clinical remission by Adapted Mayo score is 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 is the sum of three components: rectal bleeding, stool frequency, and Mayo endoscopic subscore, each measured on a scale of 0-3.
Timepoint [3] 0 0
(maintenance Week) mWeek 44
Secondary outcome [1] 0 0
Clinical remission by adapted Mayo Score Components at Week 8 - Clinical remission by Adapted Mayo score is 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 is the sum of three components: rectal bleeding, stool frequency, and Mayo endoscopic subscore, each measured on a scale of 0-3.
Timepoint [1] 0 0
Week 8
Secondary outcome [2] 0 0
Endoscopic healing at Week 8 - Endoscopic Healing is defined as an Endoscopic subscore = 1.
Endoscopic subscore is measured using scale of 0-3, where higher numbers reflect greater severity.
Timepoint [2] 0 0
Week 8
Secondary outcome [3] 0 0
Symptomatic remission at Week 8 - Symptomatic remission is defined as stool frequency score = 1 and a rectal bleeding subscore of 0.
Stool frequency score and rectal bleeding score are each measured using scale of 0-3, where higher numbers reflect greater severity.
Timepoint [3] 0 0
Week 8
Secondary outcome [4] 0 0
Clinical response by Adapted Mayo score (aMS response) at Week 8 - Clinical response is defined by Adapted Mayo score reduction = 2 and = 30%, with a reduction in the rectal bleeding subscore = 1 or an absolute subscore =1.
The Adapted Mayo score is the sum of three components: rectal bleeding, stool frequency, and Mayo endoscopic subscore, each measured on a scale of 0-3.
Timepoint [4] 0 0
Baseline to Week 8
Secondary outcome [5] 0 0
Mucosal healing at Week 8 - Mucosal healing is defined as Mayo endoscopic score = 1 and achieving histologic healing
Mayo endoscopic subscore is measured using scale of 0-3, where higher numbers reflect greater severity.
Timepoint [5] 0 0
Week 8
Secondary outcome [6] 0 0
Maintenance of clinical response at mWeek 44
Timepoint [6] 0 0
mWeek 44
Secondary outcome [7] 0 0
Endoscopic healing at mWeek 44 - Endoscopic Healing is defined as an Endoscopic subscore = 1.
Endoscopic subscore is measured using scale of 0-3, where higher numbers reflect greater severity.
Timepoint [7] 0 0
mWeek 44
Secondary outcome [8] 0 0
Symptomatic remission at mWeek 44 - Symptomatic remission is defined as stool frequency score = 1 and a rectal bleeding subscore of 0.
Stool frequency score and rectal bleeding score are each measured using scale of 0-3, where higher numbers reflect greater severity.
Timepoint [8] 0 0
mWeek 44
Secondary outcome [9] 0 0
Corticosteroid-free remission at mWeek 44
Timepoint [9] 0 0
mWeek 44
Secondary outcome [10] 0 0
Maintenance of clinical remission at mWeek 44 in those who were in remission at mWeek 0
Timepoint [10] 0 0
mWeek 44
Secondary outcome [11] 0 0
Mucosal healing at mWeek 44 - Mucosal healing is defined as Mayo endoscopic score = 1 and achieving histologic healing.
Mayo endoscopic subscore is measured using scale of 0-3, where higher numbers reflect greater severity.
Timepoint [11] 0 0
mWeek 44

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2/Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC,WA
Recruitment hospital [1] 0 0
Theravance Biopharma Investigational Site - South Brisbane
Recruitment hospital [2] 0 0
Theravance Biopharma Investigational Site - Woolloongabba
Recruitment hospital [3] 0 0
Theravance Biopharma Investigational Site - Malvern
Recruitment hospital [4] 0 0
Theravance Biopharma Investigational Site - Murdoch
Recruitment postcode(s) [1] 0 0
4101 - South Brisbane
Recruitment postcode(s) [2] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [3] 0 0
3144 - Malvern
Recruitment postcode(s) [4] 0 0
6150 - Murdoch
Recruitment outside Australia
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United States of America
State/province [1] 0 0
California
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Colorado
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Florida
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Kansas
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Kentucky
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Kaohsiung
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Zaporizhzhya
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Ukraine
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Úzhgorod

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Theravance Biopharma
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03758443
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Monitor
Address 0 0
Theravance Biopharma
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Theravance Biopharma Call Center
Address 0 0
Country 0 0
Phone 0 0
1-855-633-8479
Fax 0 0
Email 0 0
medinfo@theravance.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03758443