Ulcerative Colitis (UC)Phase 2/3RHEANCT03758443

Efficacy & Safety of TD-1473 in Ulcerative Colitis

A Phase 2/3 study testing TD-1473 Dose A, TD-1473 Dose B and TD-1473 Dose C in people with Ulcerative Colitis (UC), run by Theravance Biopharma at 188 sites in 22 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

Search all trials

Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Ulcerative Colitis (UC)
What is being tested?: TD-1473 Dose A, TD-1473 Dose B and TD-1473 Dose C
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 239 participants
Where: 188 sitesin 22 countries
Study dates: 11 Mar 2019to 20 Oct 2021
Phase: Phase 2/3
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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 locations and contacts

188 sites in 22 countries.

Country

City, postcode or hospital

188 sites in 22 countries

United States38 sites

Theravance Biopharma Investigational Site
Atlanta, Georgia, 30342
Theravance Biopharma Investigational Site
Aventura, Florida, 33180
Theravance Biopharma Investigational Site
Baltimore, Maryland, 21201
Theravance Biopharma Investigational Site
Charlotte, North Carolina, 28215
Theravance Biopharma Investigational Site
Chula Vista, California, 91911
Theravance Biopharma Investigational Site
Clearwater, Florida, 33756
Theravance Biopharma Investigational Site
Colorado Springs, Colorado, 80920
Theravance Biopharma Investigational Site
Garland, Texas, 75044
Theravance Biopharma Investigational Site
Gastonia, North Carolina, 28054
Theravance Biopharma Investigational Site
Greenville, North Carolina, 27834-3761
Theravance Biopharma Investigational Site
Greenville, South Carolina, 29615
Theravance Biopharma Investigational Site
Houston, Texas, 77002
Theravance Biopharma Investigational Site
Idaho Falls, Idaho, 83404
Theravance Biopharma Investigational Site
Kansas City, Kansas, 66160
Theravance Biopharma Investigational Site
Kansas City, Missouri, 64131
Theravance Biopharma Investigational Site
La Jolla, California, 92037
Theravance Biopharma Investigational Site
Lancaster, California, 93534
Theravance Biopharma Investigational Site
Largo, Florida, 33777
Theravance Biopharma Investigational Site
Las Vegas, Nevada, 89123
Theravance Biopharma Investigational Site
Louisville, Kentucky, 40202
Theravance Biopharma Investigational Site
Miami, Florida, 33135
Theravance Biopharma Investigational Site
Miami, Florida, 33155
Theravance Biopharma Investigational Site
Monroe, Louisiana, 71201
Theravance Biopharma Investigational Site
Nashville, Tennessee, 37212
Theravance Biopharma Investigational Site
New Port Richey, Florida, 34653
Theravance Biopharma Investigational Site
New Smyrna Beach, Florida, 32168
Theravance Biopharma Investigational Site
New York, New York, 10029
Theravance Biopharma Investigational Site
Orange, California, 92866
Theravance Biopharma Investigational Site
Orlando, Florida, 32803
Theravance Biopharma Investigational Site
Pembroke Pines, Florida, 33024
Theravance Biopharma Investigational Site
Pittsburgh, Pennsylvania, 15212
Theravance Biopharma Investigational Site
Rochester, Minnesota, 55905
Theravance Biopharma Investigational Site
Rock Hill, South Carolina, 29732
Theravance Biopharma Investigational Site
San Antonio, Texas, 78215
Theravance Biopharma Investigational Site
Smithfield, Pennsylvania, 15478
Theravance Biopharma Investigational Site
Suwanee, Georgia, 30024
Theravance Biopharma Investigational Site
Troy, Michigan, 48098
Theravance Biopharma Investigational Site
Wyoming, Michigan, 48519

Other trials in United States

Japan23 sites

Theravance Biopharma Investigational Site
Abiko, Chiba, 270-1168
Theravance Biopharma Investigational Site
Ageo, Saitama, 362-0075
Theravance Biopharma Investigational Site
Chiba, 260-0852
Theravance Biopharma Investigational Site
Fujiidera, Osaka, 583-0027
Theravance Biopharma Investigational Site
Fukuoka, 814-0180
Theravance Biopharma Investigational Site
Fukuyama-Shi, Hiroshima, 720-8520
Theravance Biopharma Investigational Site
Hatsukaichi, Hiroshima, 738-8503
Theravance Biopharma Investigational Site
Isesaki, Gunma, 372-0817
Theravance Biopharma Investigational Site
Izumiōtsu, Osaka, 595-0027
Theravance Biopharma Investigational Site
Kawasaki, Kanagawa, 211-8533
Theravance Biopharma Investigational Site
Kumamoto, 860-0004
Theravance Biopharma Investigational Site
Kurobe-shi, Toyama, 938-8502
Theravance Biopharma Investigational Site
Kurume, Fukuoka, 839-0809
Theravance Biopharma Investigational Site
Nagoya, Aichi-ken, 457-8511
Theravance Biopharma Investigational Site
Ōgaki, Gifu, 503-8502
Theravance Biopharma Investigational Site
Ōita, Oita Prefecture, 870-0033
Theravance Biopharma Investigational Site
Sakura, Chiba, 285-8741
Theravance Biopharma Investigational Site
Sendai, Miyagi, 981-3213
Theravance Biopharma Investigational Site
Suwa, Nagano, 392-8510
Theravance Biopharma Investigational Site
Tokorozawa, Saitama, 359-1114
Theravance Biopharma Investigational Site
Tokyo, 135-8577
Theravance Biopharma Investigational Site
Tokyo, 136-0075
Theravance Biopharma Investigational Site
Tokyo, 152-8902

Other trials in Japan

Poland20 sites

Theravance Biopharma Investigational Site
Krakow, Lesser Poland Voivodeship, 31-501
Theravance Biopharma Investigational Site
Ksawerów, Łódź Voivodeship, 95-054
Theravance Biopharma Investigational Site
Lodz, Lodzki, 90-302
Theravance Biopharma Investigational Site
Lodz, Łódź Voivodeship, 91-034
Theravance Biopharma Investigational Site
Piaseczno, Masovian Voivodeship, 05-500
Theravance Biopharma Investigational Site
Poznan, Greater Poland Voivodeship, 60-369
Theravance Biopharma Investigational Site
Poznan, Greater Poland Voivodeship, 61-113
Theravance Biopharma Investigational Site
Sopot, Pomeranian Voivodeship, 81-756
Theravance Biopharma Investigational Site
Staszów, Świętokrzyskie Voivodeship, 28-200
Theravance Biopharma Investigational Site
Szczecin, West Pomeranian Voivodeship, 71-434
Theravance Biopharma Investigational Site
Szczecin, 71-685
Theravance Biopharma Investigational Site
Torun, Kuyavian-Pomeranian Voivodeship, 87-100
Theravance Biopharma Investigational Site
Tychy, Silesian Voivodeship, 43-100
Theravance Biopharma Investigational Site
Warsaw, Masovian Voivodeship, 00-635
Theravance Biopharma Investigational Site
Warsaw, Masovian Voivodeship, 00-728
Theravance Biopharma Investigational Site
Warsaw, Masovian Voivodeship, 02-653
Theravance Biopharma Investigational Site
Warsaw, Masovian Voivodeship, 03-580
Theravance Biopharma Investigational Site
Włocławek, Kuyavian-Pomeranian Voivodeship, 87-800
Theravance Biopharma Investigational Site
Wroclaw, Lower Silesian Voivodeship, 53-333
Theravance Biopharma Investigational Site
Wroclaw, Lower Silesian Voivodeship, 54-416

Other trials in Poland

Ukraine17 sites

Theravance Biopharma Investigational Site
Chernivtsi, 58001
Theravance Biopharma Investigational Site
Kharkiv, 61037
Theravance Biopharma Investigational Site
Kiev, KIEV CITY, 04107
Theravance Biopharma Investigational Site
Kremenchuk, Poltava Oblast, 39617
Theravance Biopharma Investigational Site
Kyiv, Kyiv City, 01030
Theravance Biopharma Investigational Site
Kyiv, Kyiv City, 4107
Theravance Biopharma Investigational Site #2
Lviv, 79010
Theravance Biopharma Investigational Site
Lviv, 79010
Theravance Biopharma Investigational Site
Ternopil, 46001
Theravance Biopharma Investigational Site
Uzhhorod, Transcarpathian, 88000
Theravance Biopharma Investigational Site
Uzhhorod, 88009
Theravance Biopharma Investigational Site
Vinnytsia, Vinnytsya, 21005
Theravance Biopharma Investigational Site
Vinnytsia, Vinnytsya, 21029
Theravance Biopharma Investigational Site
Vinnytsia, 20129
Theravance Biopharma Investigational Site
Vinnytsia, 21018
Theravance Biopharma Investigational Site
Zaporizhzhya, 69096
Theravance Biopharma Investigational Site
Zaporizhzhya, 69600

Other trials in Ukraine

Bulgaria13 sites

Theravance Biopharma Investigational Site (2)
Pleven, 5800
Theravance Biopharma Investigational Site
Pleven, 5800
Theravance Biopharma Investigational Site
Plovdiv, 4002
Theravance Biopharma Investigational Site
Plovdiv, 4004
Theravance Biopharma Investigational Site
Rousse, 7005
Theravance Biopharma Investigational Site
Sliven, 8800
Theravance Biopharma Investigational Site
Sofia, Sofia, 1303
Theravance Biopharma Investigational Site
Sofia, Sofia, 1527
Theravance Biopharma Investigational Site
Sofia, Sofia, 1784
Theravance Biopharma Investigational Site
Sofia, 1712
Theravance Biopharma Investigational Site
Stara Zagora, 6000
Theravance Biopharma Investigational Site
Stara Zagora, 6001
Theravance Biopharma Investigational Site
Veliko Tarnovo, 5000

Other trials in Bulgaria

France9 sites

Theravance Biopharma Investigational Site
Amiens, Picardie, 80054
Theravance Biopharma Investigational Site
Lille, Hauts-de-France, 59037
Theravance Biopharma Investigational Site
Montpellier, Languedoc-roussillon, 34295
Theravance Biopharma Investigational Site
Nantes, Pays de la Loire Region, 44000
Theravance Biopharma Investigational Site
Pierre-Bénite, Auvergne-Rhône-Alpes, 69495
Theravance Biopharma Investigational Site
Reims, Champagne-ardenne, 51092
Theravance Biopharma Investigational Site
Saint-Etienne, Auvergne-Rhône-Alpes, 42055
Theravance Biopharma Investigational Site
Toulouse, Midi-pyrenees, 31059
Theravance Biopharma Investigational Site
Vandœuvre-lès-Nancy, Limousin, 54500

Other trials in France

Portugal8 sites

Theravance Biopharma Investigational Site
Coimbra, 3000-075
Theravance Biopharma Investigational Site
Guimarães, 4835-044
Theravance Biopharma Investigational Site
Leiria, 2410-197
Theravance Biopharma Investigational Site
Lisbon, 1349-019
Theravance Biopharma Investigational Site
Santa Maria da Feira, 4520-211
Theravance Biopharma Investigational Site
Senhora da Hora, 4454-513
Theravance Biopharma Investigational Site
Viana do Castelo, 4901-858
Theravance Biopharma Investigational Site
Vila Nova de Gaia, 4434502

Other trials in Portugal

Israel7 sites

Theravance Biopharma Investigational Site
Haifa, 31048
Theravance Biopharma Investigational Site
Holon, 5822012
Theravance Biopharma Investigational Site
Jerusalem, 9362410
Theravance Biopharma Investigational Site
Nahariya, 2210001
Theravance Biopharma Investigational Site
Petah Tikva, 4941492
Theravance Biopharma Investigational Site
Rehovot, 7661041
Theravance Biopharma Investigational Site
Tsrifin, Rehoboth, 7030000

Other trials in Israel

South Korea7 sites

Theravance Biopharma Investigational Site
Daegu, 42415
Theravance Biopharma Investigational Site
Seoul, 03722
Theravance Biopharma Investigational Site
Seoul, 06351
Theravance Biopharma Investigational Site
Seoul, 130-702
Theravance Biopharma Investigational Site
Seoul, 5505
Theravance Biopharma Investigational Site
Suwon, Gyeonggi-do, 16247
Theravance Biopharma Investigational Site
Wŏnju, Gangwon-do, 26426

Other trials in South Korea

Germany6 sites

Theravance Biopharma Investigational Site
Berlin, 10117
Theravance Biopharma Investigational Site
Berlin, 13353
Theravance Biopharma Investigational Site
Heidelberg, Baden-Wurttemberg, 69121
Theravance Biopharma Investigational Site
Jena, Thuringia, 07747
Theravance Biopharma Investigational Site
Kiel, Schleswig-Holstein, 24105
Theravance Biopharma Investigational Site
Ulm, Baden-Wurttemberg, 89081

Other trials in Germany

Serbia6 sites

Theravance Biopharma Investigational Site
Belgrade, 11000
Theravance Biopharma Investigational Site
Belgrade, 11080
Theravance Biopharma Investigational Site
Kragujevac, 34000
Theravance Biopharma Investigational Site
Niš, 18000
Theravance Biopharma Investigational Site
Subotica, 24000
Theravance Biopharma Investigational Site
Zrenjanin, 23000

Other trials in Serbia

Hungary5 sites

Theravance Biopharma Investigational Site
Budapest, 1088
Theravance Biopharma Investigational Site
Budapest, 1136
Theravance Biopharma Investigational Site
Debrecen, Hajdú-Bihar, 4032
Theravance Biopharma Investigational Site
Székesfehérvár, Fejér, 8000
Theravance Biopharma Investigational Site
Szekszárd, Tolna County, 7100

Other trials in Hungary

Australia4 sites

Theravance Biopharma Investigational Site
Malvern, Victoria, 3144
Theravance Biopharma Investigational Site
Murdoch, Western Australia, 6150
Theravance Biopharma Investigational Site
South Brisbane, Queensland, 4101
Theravance Biopharma Investigational Site
Woolloongabba, Queensland, 4102

Other trials in Australia

Greece4 sites

Theravance Biopharma Investigational Site
Athens, Attica, 115 27
Theravance Biopharma Investigational Site #2
Athens, Attica, 11527
Theravance Biopharma Investigational Site
Heraklion, Crete, 71110
Theravance Biopharma Investigational Site
Patra, Peloponnese, 265 04

Other trials in Greece

Spain4 sites

Theravance Biopharma Investigational Site
Barcelona, 08022
Theravance Biopharma Investigational Site
Madrid, 28006
Theravance Biopharma Investigational Site
Seville, 41013
Theravance Biopharma Investigational Site
Valencia, 46010

Other trials in Spain

Taiwan4 sites

Theravance Biopharma Investigational Site
Kaohsiung City, 83301
Theravance Biopharma Investigational Site
Taichung, 40210
Theravance Biopharma Investigational Site
Tainan, 71004
Theravance Biopharma Investigational Site
Taipei, 116

Other trials in Taiwan

Georgia3 sites

Theravance Biopharma Investigational Site
Batumi, 6010
Theravance Biopharma Investigational Site
Tbilisi, 0114
Theravance Biopharma Investigational Site
Tbilisi, 0159

Other trials in Georgia

Italy3 sites

Theravance Biopharma Investigational Site
Catanzaro, 88100
Theravance Biopharma Investigational Site
Pavia, 27100
Theravance Biopharma Investigational Site
Rozzano, Milano, 20089

Other trials in Italy

Slovakia3 sites

Theravance Biopharma Investigational Site
Nitra, 949 01
Theravance Biopharma Investigational Site
Prešov, Prešovsky, 080 01
Theravance Biopharma Investigational Site
Šahy, 936 01

Other trials in Slovakia

Romania2 sites

Theravance Biopharma Investigational Site
Bucharest, 020125
Theravance Biopharma Investigational Site
Timișoara, Timiș County, 300002

Other trials in Romania

Canada1 site

Theravance Biopharma Investigational Site
Kingston, Ontario, K7L 5G2

Other trials in Canada

South Africa1 site

Theravance Biopharma Investigational Site
Johannesburg, Gauteng, 2196

Other trials in South Africa

About this study

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

Read the detailed 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.

Conditions: Ulcerative Colitis (UC)
Being tested: TD-1473 Dose A, TD-1473 Dose B, TD-1473 Dose C, Placebo
Keywords: TD-1473, Janus kinase inhibitor, JAK inhibitor, Inflammatory Bowel Disease, IBD, Ulcerative colitis, UC, Gut selective
Medical subject headings: Colitis, Ulcerative, Inflammatory Bowel Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TD-1473 Dose ADrug
See Arm description
TD-1473 Dose BDrug
See Arm description
TD-1473 Dose CDrug
See Arm description
PlaceboDrug
See Arm description

Study groups in NCT03758443
Study group	Role	What they receive
Active Treatment TD-1473 Dose A	Experimental	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. Receives: Drug: TD-1473 Dose A
Active Treatment TD-1473 Dose B	Experimental	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. Receives: Drug: TD-1473 Dose B
Active Treatment TD-1473 Dose C	Experimental	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. Receives: Drug: TD-1473 Dose C
Placebo	Placebo comparator	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). Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline in Total Mayo Score (tMS) at 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.
Measured: Baseline to Week 8
Phase 3 Maintenance: Number of Participants Who Demonstrated Clinical Remission by Adapted Mayo Score Components at Maintenance Week (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.
Measured: mWeek 44

Secondary outcomes (4)

Number of Participants Who Demonstrated Clinical Remission by Adapted Mayo Score Components at 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.
Measured: Week 8
Phase 3 Maintenance: Number of Participants Who Demonstrated a Clinical Response by Adapted Mayo Score Components at 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.
Measured: Baseline to mWeek 44
Phase 3 Maintenance: Number of Participants Who Demonstrated Endoscopic Remission by Adapted Mayo Score Components at 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.
Measured: mWeek 44
Phase 3 Maintenance: Number of Participants Who Demonstrated Symptomatic Remission by Adapted Mayo Score Components at 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.
Measured: mWeek 44

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

11 Mar 201920 Oct 2021

First posted29 Nov 2018
Study start11 Mar 2019
Primary completion20 Oct 2021
Study completion20 Oct 2021

Why it stopped: Stopped early due to company decision. Company decision based on interim analysis results in TD-1473-0157.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Ulcerative Colitis (UC)Studies 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 2/3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: Integrated and Adaptive Design
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 239 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03758443
Sponsor's protocol ID: 0157
Other IDs: 2018-002136-24, 2018
Acronym: RHEA
Status last verified: Nov 2021
First submitted: 19 Nov 2018
Last updated: 15 Nov 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
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.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 15 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT03758443
Acronym / sponsor ID: RHEA / 0157
Conditions: Ulcerative Colitis (UC)
Keywords: TD-1473, Janus kinase inhibitor, JAK inhibitor, Inflammatory Bowel Disease, IBD, Ulcerative colitis, UC, Gut selective
Phase: Phase 2/3
Study type: Interventional
Recruitment status: TerminatedReason stopped: Stopped early due to company decision. Company decision based on interim analysis results in TD-1473-0157.
Enrolment: 239 participants (actual)
Lead sponsor: Theravance BiopharmaIndustry (pharma, biotech, devices)
Study start: 11 Mar 2019 (actual)
Primary completion: 20 Oct 2021 (actual)
Study completion: 20 Oct 2021 (actual)
First posted: 29 Nov 2018 (actual)
Results: Posted 15 Nov 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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 design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 4
Model description: Integrated and Adaptive Design

Arm	Type	Receives
Active Treatment TD-1473 Dose A	Experimental	Drug: TD-1473 Dose AParticipants 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.
Active Treatment TD-1473 Dose B	Experimental	Drug: TD-1473 Dose BParticipants 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.
Active Treatment TD-1473 Dose C	Experimental	Drug: TD-1473 Dose CParticipants 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	Placebo comparator	Drug: PlaceboParticipants 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).

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

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

Key exclusion criteria (8 listed)

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

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 Dose ASee Arm description	Drug	Active Treatment TD-1473 Dose A
TD-1473 Dose BSee Arm description	Drug	Active Treatment TD-1473 Dose B
TD-1473 Dose CSee Arm description	Drug	Active Treatment TD-1473 Dose C
PlaceboSee Arm description	Drug	Placebo

Primary outcome

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.

4 secondary outcomes

Number of Participants Who Demonstrated Clinical Remission by Adapted Mayo Score Components at Week 8
Time frame: Week 8
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
Phase 3 Maintenance: Number of Participants Who Demonstrated Endoscopic Remission by Adapted Mayo Score Components at mWeek 44
Time frame: mWeek 44
Phase 3 Maintenance: Number of Participants Who Demonstrated Symptomatic Remission by Adapted Mayo Score Components at mWeek 44
Time frame: mWeek 44

Results and safety

Results posted to the registry on 15 Nov 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo	61	55
TD-1473 20 mg	61	54
TD-1473 80 mg	59	52
TD-1473 200 mg	58	50

Primary outcome: Change From Baseline in Total Mayo Score (tMS) at Week 8

Time frame: Baseline to Week 8. Least squares mean (Standard Error). Unit: score on a scale

Measure	Induction Period: Placebo n = 56	Induction Period: TD-1473 20 mg n = 54	Induction Period: TD-1473 80 mg n = 53	Induction Period: TD-1473 200 mg n = 55
Value	-1.75 (0.341)	-2.02 (0.350)	-2.12 (0.351)	-2.40 (0.346)

Induction Period: Placebo vs Induction Period: TD-1473 20 mg: Least Square Mean Difference: -0.27 (95% CI -1.22 to 0.69), p = 0.5809, ANCOVA
Induction Period: Placebo vs Induction Period: TD-1473 80 mg: Least Square Mean Difference: -0.37 (95% CI -1.33 to 0.59), p = 0.4501, ANCOVA
Induction Period: Placebo vs Induction Period: TD-1473 200 mg: Least Square Mean Difference: -0.65 (95% CI -1.60 to 0.30), p = 0.1809, ANCOVA

Population analysed: Modified Intent-to-Treat (mITT) Analysis Set (Induction Period): Comprised all randomized participants who received at least one dose of study drug.

Primary outcome: Phase 3 Maintenance: Number of Participants Who Demonstrated Clinical Remission by Adapted Mayo Score Components at Maintenance Week (mWeek) 44

Time frame: mWeek 44. Count of participants. Unit: Participants

Measure	Maintenance Period: Placebo n = 9	Maintenance Period: TD-1473 20 mg n = 13	Maintenance Period: TD-1473 80 mg n = 11	Maintenance Period: TD-1473 200 mg n = 8
Value	4	3	5	3

Maintenance Period: Placebo vs Maintenance Period: TD-1473 20 mg: p = 0.3762, Fisher Exact
Maintenance Period: Placebo vs Maintenance Period: TD-1473 80 mg: p = 1.0000, Fisher Exact
Maintenance Period: Placebo vs Maintenance Period: TD-1473 200 mg: p = 1.0000, Fisher Exact

Population analysed: mITT Analysis Set (Maintenance Period): All participants randomized into the Phase 3 Maintenance Study who were also treated. Only participants randomized at least 44 weeks prior to database lock were included.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Induction Period: Up to Week 20 Maintenance Period: Up to Week 48. Other adverse events reported at 3% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Induction Period: Placebo	4 of 61 (6.6%)	7 of 61 (11.5%)	0 of 61
Induction Period: TD-1473 20 mg	4 of 61 (6.6%)	11 of 61 (18%)	0 of 61
Induction Period: TD-1473 80 mg	2 of 59 (3.4%)	9 of 59 (15.3%)	0 of 59
Induction Period: Placebo to TD-1473 80 mg	3 of 42 (7.1%)	4 of 42 (9.5%)	0 of 42
Induction Period: TD-1473 200 mg	4 of 58 (6.9%)	14 of 58 (24.1%)	0 of 58
Maintenance Period: Placebo	1 of 29 (3.4%)	6 of 29 (20.7%)	0 of 29
Maintenance Period: TD-1473 20 mg	2 of 31 (6.5%)	14 of 31 (45.2%)	0 of 31
Maintenance Period: TD-1473 80 mg	2 of 25 (8%)	5 of 25 (20%)	0 of 25
Maintenance Period: TD-1473 200 mg	1 of 22 (4.5%)	1 of 22 (4.5%)	0 of 22

Limitations and caveats (from the sponsor): The study was terminated early due to a company decision based on interim analysis results in TD-1473-0157. Therefore, the Phase 3 dose-confirming Induction Study was not conducted and the Maintenance Study was prematurely terminated.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Nov 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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

188 sites in 22 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing TD-1473 Dose A, TD-1473 Dose B and TD-1473 Dose C in people with Ulcerative Colitis (UC), run by Theravance Biopharma at 188 sites in 22 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: stopped early, as of the sponsor's last update on 15 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 188 sites in United States, Japan, Poland, Ukraine, Bulgaria and 17 more countries. 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 combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Nov 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Change From Baseline in Total Mayo Score (tMS) at Week 8 (time frame: Baseline to Week 8). The study lists 2 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 NCT03758443.

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 15 Nov 2022.