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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03635112




Registration number
NCT03635112
Ethics application status
Date submitted
31/07/2018
Date registered
17/08/2018
Date last updated
2/11/2020

Titles & IDs
Public title
Efficacy and Safety of TD-1473 in Crohn's Disease
Scientific title
A Phase 2 Multi-Center, Randomized, Double-Blind, Placebo?Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Induction Therapy With 2 Doses of TD-1473 in Subjects With Moderately-to-Severely Active Crohn's Disease
Secondary ID [1] 0 0
2018-001272-37
Secondary ID [2] 0 0
0173
Universal Trial Number (UTN)
Trial acronym
DIONE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Crohn's Disease 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Inflammatory bowel disease
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Oral and Gastrointestinal 0 0 0 0
Crohn's disease

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

Active Comparator: Active Treatment TD-1473 with Dose A - 1 oral Dose A daily of TD-1473 for 12 weeks in subjects with moderately to-severely active CD.
Subjects who complete Induction will continue to receive TD-1473 at Dose A in the Active Treatment Arm for up to 48 additional weeks.

Active Comparator: Active Treatment TD-1473 with Dose B - 1 oral Dose B daily of TD-1473 for 12 weeks in subjects with moderately to-severely active CD.
Subjects who complete Induction will continue to receive TD-1473 at Dose B in the Active Treatment Arm for up to 48 additional weeks.

Placebo Comparator: Placebo - 1 oral dose daily of placebo for 12 weeks in subjects with moderately to-severely active CD.
Subjects who complete Induction will receive TD-1473 at Dose A in the Active Treatment Arm for up to 48 additional weeks.


Treatment: Drugs: Placebo
Placebo will be taken daily by mouth (orally) for up to 12 weeks in the morning before eating.

Treatment: Drugs: TD-1473
TD-1473, at Dose A or Dose B depending upon arm, will be taken daily by mouth (orally) for up to 12 weeks in the morning before eating. An additional 48 weeks either at Dose A or Dose B, depending on arm, may be administered if subjects finish the 12 week induction period.

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

Outcomes
Primary outcome [1] 0 0
Improvement in Crohn's Disease Activity Index (CDAI) score from Baseline to Week 12 (PRIMARY) - To assess the effect of TD-1473 compared to placebo in improving Crohn's Disease Activity Index (CDAI) score at week 12 in subjects with moderately to severely active CD.
The CDAI score is generated using regression coefficients for eight different predictors of disease activity: severity of abdominal pain, general well-being, very soft/liquid stool frequency, extra-intestinal symptoms, need for antidiarrheal drugs, presence of an abdominal mass, body weight and hematocrit. Patients will report information regarding symptoms using a diary.
Timepoint [1] 0 0
12 weeks
Secondary outcome [1] 0 0
Clinical response measured by CDAI - To assess the effects of TD-1473 given for 12 weeks compared to placebo. CDAI clinical response is determined by a CDAI score decreasing from baseline to Week 12 by a defined value or CDAI below a defined value by Week 12. Crohn's Disease Activity Index also known as CDAI is a research tool used to quantify the symptoms of patients with Crohn's disease.
Timepoint [1] 0 0
12 weeks
Secondary outcome [2] 0 0
CDAI clinical remission - To assess the effects of TD-1473 given for 12 weeks compared to placebo. CDAI clinical remission is determined by a CDAI score being less than a defined value at Week 12. Crohn's Disease Activity Index also known as CDAI is a research tool used to quantify the symptoms of patients with Crohn's disease.
Timepoint [2] 0 0
12 weeks
Secondary outcome [3] 0 0
SES-CD (Simple Endoscopic Score for Crohn's Disease) change from baseline to Week 12 - To assess the effects of TD-1473 given for 12 weeks compared to placebo. Simple Endoscopic Score for Crohn's Disease also known as SES-CD provides a quantitative assessment of Crohn's Disease across all 5 bowel segments and allow for comparison across populations and within an individual over time.
The SES-CD incorporates 4 descriptors: the ulcer size, the proportion of surface covered by ulcer, the proportion of surface covered by other lesions, and the presence of stenosis. Each descriptor is graded from 0-3 and is scored in 5 segments (ileum, right colon, transverse colon, left colon, and rectum). The total score is calculated as the sum of all the items in each segment and can range from 0 to 60.
Timepoint [3] 0 0
12 weeks
Secondary outcome [4] 0 0
Endoscopic response - To assess the effects of TD-1473 given for 12 weeks compared to placebo. Endoscopic Response is determined by a reduction of SES-CD (Simple Endoscopic Score for Crohn's Disease is also known as SES-CD) score or Endoscopic Remission at Week 12.
Simple Endoscopic Score for Crohn's Disease also known as SES-CD provides a quantitative assessment of Crohn's Disease across all 5 bowel segments and allow for comparison across populations and within an individual over time.
The SES-CD incorporates 4 descriptors: the ulcer size, the proportion of surface covered by ulcer, the proportion of surface covered by other lesions, and the presence of stenosis. Each descriptor is graded from 0-3 and is scored in 5 segments (ileum, right colon, transverse colon, left colon, and rectum). The total score is calculated as the sum of all the items in each segment and can range from 0 to 60.
Timepoint [4] 0 0
12 weeks
Secondary outcome [5] 0 0
Stool Frequency and Abdominal Pain (SFAP) clinical remission - To assess the effects of TD-1473 given for 12 weeks compared to placebo. Stool Frequency and Abdominal Pain (SFAP) clinical remission is determined using a patient reported Abdominal Pain score [which uses a scale of 0 - 3 with 0 representing 'no pain' and 3 representing 'severe pain'] and patient reported Stool Frequency.
Timepoint [5] 0 0
12 weeks

Eligibility
Key inclusion criteria
- Is at least 18 years of age at screening

- Males and females with clinical evidence of Crohn's disease for at least 3 months
duration at screening

- Moderately-to-severely active Crohn's Disease at baseline, as defined by a Crohn's
Disease Activity Index (CDAI) score of 220-450 inclusive

- SES-CD score of = 3 with ulceration (corresponding to a score of 1) in at least 1 of
the 5 ileocolonic segments on the Ulcerated Surface subscore of the SES-CD]

- Is corticosteroid-dependent or has demonstrated inadequate response, or intolerance to
conventional therapy (aminosalicylates, corticosteroids and immunomodulators such as
azathioprine, 6-mercaptopurine, or methotrexate) or biologics (e.g., anti-TNF therapy,
anti-IL-12/23 (anti-interleukin), anti-integrin).

- 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
- Is currently receiving biologic (anti-TNF, anti-integrin, or anti-IL12/23) therapy

- Has a current bacterial, parasitic, fungal, or viral infection

- Has clinically significant abnormalities in laboratory evaluations

- Prior exposure or potential exposure to a JAK inhibitor that was stopped due to
intolerance or lack of efficacy

- Subject has participated in another clinical trial of an investigational drug (or
medical device) within 30 days prior to Screening or 5x the half-life of the
investigational drug, whichever is longer, or is currently participating in another
trial of an investigational drug (or medical device)

- Subject has failed = 3 biologic agents of 3 different mechanisms of action (i.e.,
anti-TNF, anti-integrin, and anti-IL12/23)

- 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
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)
NSW,SA,WA
Recruitment hospital [1] 0 0
Theravance Biopharma Investigational Site - Bankstown
Recruitment hospital [2] 0 0
Theravance Biopharma Investigational Site - Elizabeth Vale
Recruitment hospital [3] 0 0
Theravance Biopharma Investigational Site - Perth
Recruitment postcode(s) [1] 0 0
2200 - Bankstown
Recruitment postcode(s) [2] 0 0
5112 - Elizabeth Vale
Recruitment postcode(s) [3] 0 0
6000 - Perth
Recruitment outside Australia
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United States of America
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Alabama
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Theravance Biopharma
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
A Phase 2 study to evaluate the efficacy, safety and tolerability of TD-1473 in subjects with
moderately-to-severely active Crohn's Disease with up to 48 weeks of treatment.
Trial website
https://clinicaltrials.gov/show/NCT03635112
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/NCT03635112