Ulcerative Colitis, Active ModeratePhase 1NCT02818686
TD-1473 for Active Ulcerative Colitis (UC)
A Phase 1 study testing TD-1473 in people with Ulcerative Colitis, Active Moderate and Ulcerative Colitis, Active Severe, run by Theravance Biopharma at 8 sites in 4 countries.
Trial summary
This study is designed to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of TD-1473 in subjects with moderately-to-severely active UC over 28 days. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Ulcerative Colitis, Active Moderate, Ulcerative Colitis, Active Severe
- What is being tested?
- TD-1473
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 8 sitesin 4 countries
- Study dates
- 3 Oct 2016to 29 Mar 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Has a history of ulcerative colitis diagnosis at least 3 months prior to screening
- Is intolerant, refractory, or only partially responsive to aminosalicylates, corticosteroids, immunomodulators, or biologics. If subject is currently receiving an oral aminosalicylate, he or she is eligible and can stay on that dose of aminosalicylate provided the dose has been stable for at least 2 weeks prior to screening. If the subject is currently receiving an oral corticosteroid, he or she is eligible if the dose is equivalent to or less than prednisone 20 mg/day or budesonide 9 mg/day and stable for at least 2 weeks prior to screening sigmoidoscopy if the subject has been on corticosteroids for more than 2 weeks.
- Has a rectal bleeding score ≥ 1 and a bowel frequency score ≥ 1 on the patient-reported outcome 2 (PRO2) on screening sigmoidoscopy day and on Day 1 in addition to a modified Mayo endoscopic subscore of ≥ 2 during screening
- Women of childbearing potential must have a negative pregnancy test and either abstain from sexual intercourse or use a highly effective method of birth control
- Willing and able to give informed consent
- Additional inclusion criteria apply
Who cannot join
- Has fulminant colitis, toxic megacolon, primary sclerosing cholangitis, Crohn's disease, history of colitis-associated colonic dysplasia, active peptic ulcer disease
- Medications of exclusion: a) azathioprine, 6-mercaptopurine, or methotrexate within the 28 days prior to Day 1, b) adalimumab, infliximab, golimumab, etanercept, or certolizumab within the 60 days prior to Day 1, c) intravenous corticosteroids within the 14 days prior to Day 1, d) topical mesalamine or steroid (i.e., enemas or suppositories) within the 14 days prior to Day 1, e) any prior exposure to mycophenolic acid, tacrolimus, sirolimus, cyclosporine, natalizumab, rituximab, efalizumab, ustekinumab, fingolimod, or thalidomide, f) NSAIDs on a daily basis, g) tofacitinib within the 60 days prior to Day 1; h) vedolizumab within 120 days prior to Day 1
- Has a current bacterial, parasitic, fungal, or viral infection
- Is positive for hepatitis A, B or C, HIV or tuberculosis
- Has clinically significant abnormalities in laboratory evaluations
- Participated in another clinical trial of an investigational drug (or medical device) within 30 days prior to screening (or within 60 days prior to screening if investigational drug was a biologic or another Janus kinase (JAK) inhibitor, or is currently participating in another trial of an investigational drug (or medical device)
- Use of prescription medications started or with a dose adjustment within 4 weeks prior to study enrollment, or over-the-counter medications or supplements started or with a dose adjustment within 2 weeks prior study enrollment. Anti-diarrheal medications are allowed only if dose has been stable at least 2 weeks prior to study enrollment
- Additional exclusion criteria apply
Trial locations and contacts
8 sites in 4 countries.
8 sites in 4 countries
United States5 sites
Theravance Biopharma Investigational Site
Hermitage, Tennessee, 37076
Theravance Biopharma Investigational Site
Houston, Texas, 77004
Theravance Biopharma Investigational Site
Monroe, Louisiana, 71201
Theravance Biopharma Investigational Site
San Antonio, Texas, 78215
Theravance Biopharma Investigational Site
Scottsdale, Arizona, 85259
About this study
Official title: A Phase 1b Multi-Center, Randomized, Double-Blind, Multi-Dose, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacodynamics, and Plasma Exposure of TD-1473 in Subjects With Moderately-to-Severely Active Ulcerative Colitis
This study is designed to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of TD-1473 in subjects with moderately-to-severely active UC over 28 days. This exploratory study will also serve as a signal seeking endeavor to demonstrate biologic effect associated with TD-1473 through biomarker analysis and clinical, endoscopic, and histologic assessments.
- Being tested
- TD-1473, Placebo
- Keywords
- Ulcerative Colitis, Active Moderate and Severe
- Medical subject headings
- Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TD-1473Drug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| TD-1473 low dose | Experimental | 10 subjects will be randomized to receive low-dose TD-1473 orally daily for 28 days Receives: Drug: TD-1473 |
| TD-1473 mid dose | Experimental | 10 subjects will be randomized to receive mid-dose TD-1473 orally daily for 28 days Receives: Drug: TD-1473 |
| TD-1473 high dose | Experimental | 10 subjects will be randomized to receive high-dose TD-1473 orally daily for 28 days Receives: Drug: TD-1473 |
| Placebo | Placebo comparator | 10 subjects will be randomized to receive placebo orally daily for 28 days Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment-emergent Adverse Events (TEAE)
Number of participants who experience one or more treatment-emergent Adverse Events (TEAE)
Measured: Baseline to end of follow-up (a maximum of 42 days)
Moderate or Severe Treatment-emergent Adverse Events (TEAE)
Number of participants who experience one or more moderate or severe treatment-emergent Adverse Events (TEAE)
Measured: Baseline to end of follow-up (a maximum of 42 days)
Serious Treatment-emergent Adverse Events (TEAE)
Number of participants who experience one or more serious treatment-emergent Adverse Events (TEAE)
Measured: Baseline to end of follow-up (a maximum of 42 days)
Clinical Laboratory Measurements
Number of participants who experienced a Clinically Significant Clinical Laboratory Measurements
Measured: Baseline to end of follow-up (a maximum of 42 days)
Electrocardiogram
Number of participants who experienced a Clinically Significant Electrocardiogram (ECG) Result
Measured: Baseline to Day 14
Vital Signs
Number of participants who experienced a Clinically Significant Vital Sign Measurement
Measured: Baseline to end of follow-up (a maximum of 42 days)
Cmax in plasma
Maximum Observed Plasma Concentration of TD-1473
Measured: Day 1 and Day 14
Tmax in plasma
Time to Reach Maximum Observed Plasma Concentration (Cmax) of TD-1473
Measured: Day 1 and Day 14
Tlast in plasma
Time to Last Quantifiable Concentration of TD-1473
Measured: Day 1 and Day 14
Ctrough in plasma
Trough Concentration of TD-1473
Measured: Day 14 (Pre-dose)
AUC0-4 in plasma
Area Under the Concentration-time Curve from Time Zero to 4 hours Post-Dose of TD-1473
Measured: Day 1 and Day 14
Ctissue in plasma
Tissue Concentration of TD-1473
Measured: Day 28
Secondary outcomes (3)
C-reactive protein (CRP)
Mean Change in Serum C-reactive Protein (CRP)
Measured: Baseline, Day 14 and Day 28
Fecal Calprotectin
Mean Change in Fecal Calprotectin
Measured: Baseline and Day 28
Partial Mayo score
Mean Change in Partial Mayo Score
Measured: Baseline, Day 14 and Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2016 (estimated)
- Study start3 Oct 2016
- Primary completion29 Mar 2018
- Study completion29 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ulcerative Colitis, Active ModerateStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Theravance Biopharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, Study director, Theravance Biopharma
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02818686
- Sponsor's protocol ID
- 0144
- Other IDs
- 2016-001633-27, 2016
- Status last verified
- Sep 2021
- First submitted
- 23 Jun 2016
- Last updated
- 30 Sep 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Theravance Biopharma, Inc. will not be sharing individual de-identified participant data or other relevant study documents.
Publications
Sandborn WJ, Nguyen DD, Beattie DT, Brassil P, Krey W, Woo J, Situ E, Sana R, Sandvik E, Pulido-Rios MT, Bhandari R, Leighton JA, Ganeshappa R, Boyle DL, Abhyankar B, Kleinschek MA, Graham RA, Panes J. Development of Gut-Selective Pan-Janus Kinase Inhibitor TD-1473 for Ulcerative Colitis: A Translational Medicine Programme. J Crohns Colitis. 2020 Sep 16;14(9):1202-1213. doi: 10.1093/ecco-jcc/jjaa049.
PubMed 32161949
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b Multi-Center, Randomized, Double-Blind, Multi-Dose, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacodynamics, and Plasma Exposure of TD-1473 in Subjects With Moderately-to-Severely Active Ulcerative Colitis
- ClinicalTrials.gov ID
- NCT02818686
- Acronym / sponsor ID
- 0144
- Keywords
- Ulcerative Colitis, Active Moderate and Severe
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Theravance BiopharmaIndustry (pharma, biotech, devices)
- Study start
- 3 Oct 2016 (actual)
- Primary completion
- 29 Mar 2018 (actual)
- Study completion
- 29 Mar 2018 (actual)
- First posted
- 30 Jun 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is designed to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of TD-1473 in subjects with moderately-to-severely active UC over 28 days. This exploratory study will also serve as a signal seeking endeavor to demonstrate biologic effect associated with TD-1473 through biomarker analysis and clinical, endoscopic, and histologic assessments.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| TD-1473 low dose | Experimental | Drug: TD-147310 subjects will be randomized to receive low-dose TD-1473 orally daily for 28 days |
| TD-1473 mid dose | Experimental | Drug: TD-147310 subjects will be randomized to receive mid-dose TD-1473 orally daily for 28 days |
| TD-1473 high dose | Experimental | Drug: TD-147310 subjects will be randomized to receive high-dose TD-1473 orally daily for 28 days |
| Placebo | Placebo comparator | Drug: Placebo10 subjects will be randomized to receive placebo orally daily for 28 days |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Has a history of ulcerative colitis diagnosis at least 3 months prior to screening
- Is intolerant, refractory, or only partially responsive to aminosalicylates, corticosteroids, immunomodulators, or biologics. If subject is currently receiving an oral aminosalicylate, he or she is eligible and can stay on that dose of aminosalicylate provided the dose has been stable for at least 2 weeks prior to screening. If the subject is currently receiving an oral corticosteroid, he or she is eligible if the dose is equivalent to or less than prednisone 20 mg/day or budesonide 9 mg/day and stable for at least 2 weeks prior to screening sigmoidoscopy if the subject has been on corticosteroids for more than 2 weeks.
- Has a rectal bleeding score ≥ 1 and a bowel frequency score ≥ 1 on the patient-reported outcome 2 (PRO2) on screening sigmoidoscopy day and on Day 1 in addition to a modified Mayo endoscopic subscore of ≥ 2 during screening
- Women of childbearing potential must have a negative pregnancy test and either abstain from sexual intercourse or use a highly effective method of birth control
- Willing and able to give informed consent
Key exclusion criteria (8 listed)
- Has fulminant colitis, toxic megacolon, primary sclerosing cholangitis, Crohn's disease, history of colitis-associated colonic dysplasia, active peptic ulcer disease
- Medications of exclusion: a) azathioprine, 6-mercaptopurine, or methotrexate within the 28 days prior to Day 1, b) adalimumab, infliximab, golimumab, etanercept, or certolizumab within the 60 days prior to Day 1, c) intravenous corticosteroids within the 14 days prior to Day 1, d) topical mesalamine or steroid (i.e., enemas or suppositories) within the 14 days prior to Day 1, e) any prior exposure to mycophenolic acid, tacrolimus, sirolimus, cyclosporine, natalizumab, rituximab, efalizumab, ustekinumab, fingolimod, or thalidomide, f) NSAIDs on a daily basis, g) tofacitinib within the 60 days prior to Day 1; h) vedolizumab within 120 days prior to Day 1
- Has a current bacterial, parasitic, fungal, or viral infection
- Is positive for hepatitis A, B or C, HIV or tuberculosis
- Has clinically significant abnormalities in laboratory evaluations
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TD-1473 | Drug | TD-1473 high dose, TD-1473 low dose, TD-1473 mid dose |
| Placebo | Drug | Placebo |
Primary outcome
Treatment-emergent Adverse Events (TEAE)
Time frame: Baseline to end of follow-up (a maximum of 42 days)
Number of participants who experience one or more treatment-emergent Adverse Events (TEAE)
Moderate or Severe Treatment-emergent Adverse Events (TEAE)
Time frame: Baseline to end of follow-up (a maximum of 42 days)
Number of participants who experience one or more moderate or severe treatment-emergent Adverse Events (TEAE)
Serious Treatment-emergent Adverse Events (TEAE)
Time frame: Baseline to end of follow-up (a maximum of 42 days)
Number of participants who experience one or more serious treatment-emergent Adverse Events (TEAE)
Clinical Laboratory Measurements
Time frame: Baseline to end of follow-up (a maximum of 42 days)
Number of participants who experienced a Clinically Significant Clinical Laboratory Measurements
Electrocardiogram
Time frame: Baseline to Day 14
Number of participants who experienced a Clinically Significant Electrocardiogram (ECG) Result
Vital Signs
Time frame: Baseline to end of follow-up (a maximum of 42 days)
Number of participants who experienced a Clinically Significant Vital Sign Measurement
Cmax in plasma
Time frame: Day 1 and Day 14
Maximum Observed Plasma Concentration of TD-1473
Tmax in plasma
Time frame: Day 1 and Day 14
Time to Reach Maximum Observed Plasma Concentration (Cmax) of TD-1473
Tlast in plasma
Time frame: Day 1 and Day 14
Time to Last Quantifiable Concentration of TD-1473
Ctrough in plasma
Time frame: Day 14 (Pre-dose)
Trough Concentration of TD-1473
AUC0-4 in plasma
Time frame: Day 1 and Day 14
Area Under the Concentration-time Curve from Time Zero to 4 hours Post-Dose of TD-1473
Ctissue in plasma
Time frame: Day 28
Tissue Concentration of TD-1473
3 secondary outcomes
C-reactive protein (CRP)
Time frame: Baseline, Day 14 and Day 28
Fecal Calprotectin
Time frame: Baseline and Day 28
Partial Mayo score
Time frame: Baseline, Day 14 and Day 28
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2021.
- Derived from this study: PubMed 32161949Sandborn WJ, Nguyen DD, Beattie DT, Brassil P, Krey W, Woo J, Situ E, Sana R, Sandvik E, Pulido-Rios MT, Bhandari R, Leighton JA, Ganeshappa R, Boyle DL, Abhyankar B, Kleinschek MA, Graham RA, Panes J. Development of Gut-Selective Pan-Janus Kinase Inhibitor TD-1473 for Ulcerative Colitis: A Translational Medicine Programme. J Crohns Colitis. 2020 Sep 16;14(9):1202-1213. doi: 10.1093/ecco-jcc/jjaa049.
- Individual participant dataSharing planned: No. Theravance Biopharma, Inc. will not be sharing individual de-identified participant data or other relevant study documents.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Monitor study director
Theravance Biopharma
8 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TD-1473 in people with Ulcerative Colitis, Active Moderate and Ulcerative Colitis, Active Severe, run by Theravance Biopharma at 8 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States, Georgia, Moldova, Romania. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment-emergent Adverse Events (TEAE) (time frame: Baseline to end of follow-up (a maximum of 42 days)). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02818686, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2021.