Clinical trial NCT03758443: Efficacy & Safety of TD-1473 in Ulcerative Colitis
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Ulcerative Colitis (UC)
Keywords: TD-1473
Janus kinase inhibitor
JAK inhibitor
Inflammatory Bowel Disease
IBD
Ulcerative colitis
UC
Gut selective
Lead sponsor: Theravance Biopharma
Sponsor class: INDUSTRY
First posted: 2018-11-29
Enrollment: 239
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Integrated and Adaptive Design
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline in Total Mayo Score (tMS) at Week 8
timeFrame: Baseline to Week 8
measure: Phase 3 Maintenance: Number of Participants Who Demonstrated Clinical Remission by Adapted Mayo Score Components at Maintenance Week (mWeek) 44
timeFrame: mWeek 44
Secondary outcomes:
measure: Number of Participants Who Demonstrated Clinical Remission by Adapted Mayo Score Components at Week 8
timeFrame: Week 8
measure: Phase 3 Maintenance: Number of Participants Who Demonstrated a Clinical Response by Adapted Mayo Score Components at mWeek 44
timeFrame: Baseline to mWeek 44
measure: Phase 3 Maintenance: Number of Participants Who Demonstrated Endoscopic Remission by Adapted Mayo Score Components at mWeek 44
timeFrame: mWeek 44
measure: Phase 3 Maintenance: Number of Participants Who Demonstrated Symptomatic Remission by Adapted Mayo Score Components at mWeek 44
timeFrame: mWeek 44
Other outcomes:
Locations:
city: Chula Vista
country: United States
facility: Theravance Biopharma Investigational Site
state: California
city: La Jolla
country: United States
facility: Theravance Biopharma Investigational Site
state: California
city: Lancaster
country: United States
facility: Theravance Biopharma Investigational Site
state: California
city: Orange
country: United States
facility: Theravance Biopharma Investigational Site
state: California
city: Colorado Springs
country: United States
facility: Theravance Biopharma Investigational Site
state: Colorado
city: Aventura
country: United States
facility: Theravance Biopharma Investigational Site
state: Florida
city: Clearwater
country: United States
facility: Theravance Biopharma Investigational Site
state: Florida
city: Largo
country: United States
facility: Theravance Biopharma Investigational Site
state: Florida
city: Miami
country: United States
facility: Theravance Biopharma Investigational Site
state: Florida
city: Miami
country: United States
facility: Theravance Biopharma Investigational Site
state: Florida
city: New Port Richey
country: United States
facility: Theravance Biopharma Investigational Site
state: Florida
city: New Smyrna Beach
country: United States
facility: Theravance Biopharma Investigational Site
state: Florida
city: Orlando
country: United States
facility: Theravance Biopharma Investigational Site
state: Florida
city: Pembroke Pines
country: United States
facility: Theravance Biopharma Investigational Site
state: Florida
city: Atlanta
country: United States
facility: Theravance Biopharma Investigational Site
state: Georgia
city: Suwanee
country: United States
facility: Theravance Biopharma Investigational Site
state: Georgia
city: Idaho Falls
country: United States
facility: Theravance Biopharma Investigational Site
state: Idaho
city: Kansas City
country: United States
facility: Theravance Biopharma Investigational Site
state: Kansas
city: Louisville
country: United States
facility: Theravance Biopharma Investigational Site
state: Kentucky
city: Monroe
country: United States
facility: Theravance Biopharma Investigational Site
state: Louisiana
city: Baltimore
country: United States
facility: Theravance Biopharma Investigational Site
state: Maryland
city: Troy
country: United States
facility: Theravance Biopharma Investigational Site
state: Michigan
city: Wyoming
country: United States
facility: Theravance Biopharma Investigational Site
state: Michigan
city: Rochester
country: United States
facility: Theravance Biopharma Investigational Site
state: Minnesota
city: Kansas City
country: United States
facility: Theravance Biopharma Investigational Site
state: Missouri
city: Las Vegas
country: United States
facility: Theravance Biopharma Investigational Site
state: Nevada
city: New York
country: United States
facility: Theravance Biopharma Investigational Site
state: New York
city: Charlotte
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facility: Theravance Biopharma Investigational Site
state: North Carolina
city: Gastonia
country: United States
facility: Theravance Biopharma Investigational Site
state: North Carolina
city: Greenville
country: United States
facility: Theravance Biopharma Investigational Site
state: North Carolina
city: Pittsburgh
country: United States
facility: Theravance Biopharma Investigational Site
state: Pennsylvania
city: Smithfield
country: United States
facility: Theravance Biopharma Investigational Site
state: Pennsylvania
city: Greenville
country: United States
facility: Theravance Biopharma Investigational Site
state: South Carolina
city: Rock Hill
country: United States
facility: Theravance Biopharma Investigational Site
state: South Carolina
city: Nashville
country: United States
facility: Theravance Biopharma Investigational Site
state: Tennessee
city: Garland
country: United States
facility: Theravance Biopharma Investigational Site
state: Texas
city: Houston
country: United States
facility: Theravance Biopharma Investigational Site
state: Texas
city: San Antonio
country: United States
facility: Theravance Biopharma Investigational Site
state: Texas
city: South Brisbane
country: Australia
facility: Theravance Biopharma Investigational Site
state: Queensland
city: Woolloongabba
country: Australia
facility: Theravance Biopharma Investigational Site
state: Queensland
city: Malvern
country: Australia
facility: Theravance Biopharma Investigational Site
state: Victoria
city: Murdoch
country: Australia
facility: Theravance Biopharma Investigational Site
state: Western Australia
city: Sofia
country: Bulgaria
facility: Theravance Biopharma Investigational Site
state: Sofiya
city: Sofia
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facility: Theravance Biopharma Investigational Site
state: Sofiya
city: Sofia
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facility: Theravance Biopharma Investigational Site
state: Sofiya
city: Pleven
country: Bulgaria
facility: Theravance Biopharma Investigational Site (2)
city: Pleven
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facility: Theravance Biopharma Investigational Site
city: Plovdiv
country: Bulgaria
facility: Theravance Biopharma Investigational Site
city: Plovdiv
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city: Ruse
country: Bulgaria
facility: Theravance Biopharma Investigational Site
city: Sliven
country: Bulgaria
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city: Sofia
country: Bulgaria
facility: Theravance Biopharma Investigational Site
city: Stara Zagora
country: Bulgaria
facility: Theravance Biopharma Investigational Site
city: Stara Zagora
country: Bulgaria
facility: Theravance Biopharma Investigational Site
city: Veliko Tarnovo
country: Bulgaria
facility: Theravance Biopharma Investigational Site
city: Kingston
country: Canada
facility: Theravance Biopharma Investigational Site
state: Ontario
city: Reims
country: France
facility: Theravance Biopharma Investigational Site
state: Champagne-ardenne
city: Montpellier Cedex 5
country: France
facility: Theravance Biopharma Investigational Site
state: Languedoc-roussillon
city: Vandœuvre-lès-Nancy Cedex
country: France
facility: Theravance Biopharma Investigational Site
state: Limousin
city: Toulouse Cedex 9
country: France
facility: Theravance Biopharma Investigational Site
state: Midi-pyrenees
city: Lille Cedex
country: France
facility: Theravance Biopharma Investigational Site
state: NORD Pas-de-calais
city: Nantes
country: France
facility: Theravance Biopharma Investigational Site
state: PAYS DE LA Loire
city: Amiens Cedex 1
country: France
facility: Theravance Biopharma Investigational Site
state: Picardie
city: Pierre Bénite
country: France
facility: Theravance Biopharma Investigational Site
state: Rhone-alpes
city: Saint-Etienne
country: France
facility: Theravance Biopharma Investigational Site
state: Rhone-alpes
city: Batumi
country: Georgia
facility: Theravance Biopharma Investigational Site
city: Tbilisi
country: Georgia
facility: Theravance Biopharma Investigational Site
city: Tbilisi
country: Georgia
facility: Theravance Biopharma Investigational Site
city: Heidelberg
country: Germany
facility: Theravance Biopharma Investigational Site
state: Baden-wuerttemberg
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facility: Theravance Biopharma Investigational Site
state: Baden-wuerttemberg
city: Kiel
country: Germany
facility: Theravance Biopharma Investigational Site
state: Schleswig-holstein
city: Jena
country: Germany
facility: Theravance Biopharma Investigational Site
state: Thuringen
city: Berlin
country: Germany
facility: Theravance Biopharma Investigational Site
city: Berlin
country: Germany
facility: Theravance Biopharma Investigational Site
city: Athens
country: Greece
facility: Theravance Biopharma Investigational Site
state: Attica
city: Athens
country: Greece
facility: Theravance Biopharma Investigational Site #2
state: Attica
city: Heraklion
country: Greece
facility: Theravance Biopharma Investigational Site
state: Crete
city: Patra
country: Greece
facility: Theravance Biopharma Investigational Site
state: Peloponnese
city: Székesfehérvár
country: Hungary
facility: Theravance Biopharma Investigational Site
state: Fejer
city: Debrecen
country: Hungary
facility: Theravance Biopharma Investigational Site
state: Hajdu-bihar
city: Szekszard
country: Hungary
facility: Theravance Biopharma Investigational Site
state: Tolna
city: Budapest
country: Hungary
facility: Theravance Biopharma Investigational Site
city: Budapest
country: Hungary
facility: Theravance Biopharma Investigational Site
city: Zerifin
country: Israel
facility: Theravance Biopharma Investigational Site
state: Rehoboth
city: Haifa
country: Israel
facility: Theravance Biopharma Investigational Site
city: Holon
country: Israel
facility: Theravance Biopharma Investigational Site
city: Jerusalem
country: Israel
facility: Theravance Biopharma Investigational Site
city: Nahariya
country: Israel
facility: Theravance Biopharma Investigational Site
city: Petah Tikva
country: Israel
facility: Theravance Biopharma Investigational Site
city: Rehovot
country: Israel
facility: Theravance Biopharma Investigational Site
city: Rozzano
country: Italy
facility: Theravance Biopharma Investigational Site
state: Milano
city: Catanzaro
country: Italy
facility: Theravance Biopharma Investigational Site
city: Pavia
country: Italy
facility: Theravance Biopharma Investigational Site
city: Nagoya
country: Japan
facility: Theravance Biopharma Investigational Site
state: Aichi
city: Abiko
country: Japan
facility: Theravance Biopharma Investigational Site
state: Chiba
city: Sakura
country: Japan
facility: Theravance Biopharma Investigational Site
state: Chiba
city: Kurume
country: Japan
facility: Theravance Biopharma Investigational Site
state: Fukuoka
city: Ōgaki
country: Japan
facility: Theravance Biopharma Investigational Site
state: Gifu
city: Isesaki
country: Japan
facility: Theravance Biopharma Investigational Site
state: Gunma
city: Fukuyama-Shi
country: Japan
facility: Theravance Biopharma Investigational Site
state: Hiroshima-ken
city: Hatsukaichi
country: Japan
facility: Theravance Biopharma Investigational Site
state: Hiroshima
city: Kawasaki
country: Japan
facility: Theravance Biopharma Investigational Site
state: Kanagawa
city: Sendai
country: Japan
facility: Theravance Biopharma Investigational Site
state: Miyagi
city: Suwa
country: Japan
facility: Theravance Biopharma Investigational Site
state: Nagano
city: Ōita
country: Japan
facility: Theravance Biopharma Investigational Site
state: Oita
city: Fujiidera
country: Japan
facility: Theravance Biopharma Investigational Site
state: Osaka Fu
city: Izumiotsu
country: Japan
facility: Theravance Biopharma Investigational Site
state: Osaka
city: Ageo
country: Japan
facility: Theravance Biopharma Investigational Site
state: Saitama Ken
city: Tokorozawa
country: Japan
facility: Theravance Biopharma Investigational Site
state: Saitama
city: Kurobe
country: Japan
facility: Theravance Biopharma Investigational Site
state: Toyama
city: Chiba
country: Japan
facility: Theravance Biopharma Investigational Site
city: Fukuoka
country: Japan
facility: Theravance Biopharma Investigational Site
city: Kumamoto
country: Japan
facility: Theravance Biopharma Investigational Site
city: Tokyo
country: Japan
facility: Theravance Biopharma Investigational Site
city: Tokyo
country: Japan
facility: Theravance Biopharma Investigational Site
city: Tokyo
country: Japan
facility: Theravance Biopharma Investigational Site
city: Wŏnju
country: Korea, Republic of
facility: Theravance Biopharma Investigational Site
state: Gangwon-do
city: Suwon
country: Korea, Republic of
facility: Theravance Biopharma Investigational Site
state: Gyeonggi-do
city: Daegu
country: Korea, Republic of
facility: Theravance Biopharma Investigational Site
city: Seoul
country: Korea, Republic of
facility: Theravance Biopharma Investigational Site
city: Seoul
country: Korea, Republic of
facility: Theravance Biopharma Investigational Site
city: Seoul
country: Korea, Republic of
facility: Theravance Biopharma Investigational Site
city: Seoul
country: Korea, Republic of
facility: Theravance Biopharma Investigational Site
city: Wrocław
country: Poland
facility: Theravance Biopharma Investigational Site
state: Dolnoslaskie
city: Wrocław
country: Poland
facility: Theravance Biopharma Investigational Site
state: Dolnoslaskie
city: Toruń
country: Poland
facility: Theravance Biopharma Investigational Site
state: Kujawsko-Pomorskie
city: Włocławek
country: Poland
facility: Theravance Biopharma Investigational Site
state: Kujawsko-Pomorskie
city: Ksawerów
country: Poland
facility: Theravance Biopharma Investigational Site
state: Lodzkie
city: Łódź
country: Poland
facility: Theravance Biopharma Investigational Site
state: Lodzkie
city: Łódź
country: Poland
facility: Theravance Biopharma Investigational Site
state: Lodzki
city: Kraków
country: Poland
facility: Theravance Biopharma Investigational Site
state: Malopolskie
city: Piaseczno
country: Poland
facility: Theravance Biopharma Investigational Site
state: Mazowieckie
city: Warszawa
country: Poland
facility: Theravance Biopharma Investigational Site
state: Mazowieckie
city: Warszawa
country: Poland
facility: Theravance Biopharma Investigational Site
state: Mazowieckie
city: Warszawa
country: Poland
facility: Theravance Biopharma Investigational Site
state: Mazowieckie
city: Warszawa
country: Poland
facility: Theravance Biopharma Investigational Site
state: Mazowieckie
city: Sopot
country: Poland
facility: Theravance Biopharma Investigational Site
state: Pomorskie
city: Tychy
country: Poland
facility: Theravance Biopharma Investigational Site
state: Slaskie
city: Staszów
country: Poland
facility: Theravance Biopharma Investigational Site
state: Swietokrzyskie
city: Poznań
country: Poland
facility: Theravance Biopharma Investigational Site
state: Wielkopolskie
city: Poznań
country: Poland
facility: Theravance Biopharma Investigational Site
state: Wielkopolskie
city: Szczecin
country: Poland
facility: Theravance Biopharma Investigational Site
state: Zachodniopomorskie
city: Szczecin
country: Poland
facility: Theravance Biopharma Investigational Site
city: Coimbra
country: Portugal
facility: Theravance Biopharma Investigational Site
city: Guimarães
country: Portugal
facility: Theravance Biopharma Investigational Site
city: Leiria
country: Portugal
facility: Theravance Biopharma Investigational Site
city: Lisboa
country: Portugal
facility: Theravance Biopharma Investigational Site
city: Santa Maria Da Feira
country: Portugal
facility: Theravance Biopharma Investigational Site
city: Senhora da Hora
country: Portugal
facility: Theravance Biopharma Investigational Site
city: Viana Do Castelo
country: Portugal
facility: Theravance Biopharma Investigational Site
city: Vila Nova De Gaia
country: Portugal
facility: Theravance Biopharma Investigational Site
city: Timişoara
country: Romania
facility: Theravance Biopharma Investigational Site
state: Timis
city: Bucuresti
country: Romania
facility: Theravance Biopharma Investigational Site
city: Belgrade
country: Serbia
facility: Theravance Biopharma Investigational Site
city: Belgrade
country: Serbia
facility: Theravance Biopharma Investigational Site
city: Kragujevac
country: Serbia
facility: Theravance Biopharma Investigational Site
city: Nis
country: Serbia
facility: Theravance Biopharma Investigational Site
city: Subotica
country: Serbia
facility: Theravance Biopharma Investigational Site
city: Zrenjanin
country: Serbia
facility: Theravance Biopharma Investigational Site
city: Prešov
country: Slovakia
facility: Theravance Biopharma Investigational Site
state: Prešovsky
city: Nitra
country: Slovakia
facility: Theravance Biopharma Investigational Site
city: Šahy
country: Slovakia
facility: Theravance Biopharma Investigational Site
city: Johannesburg
country: South Africa
facility: Theravance Biopharma Investigational Site
state: Gauteng
city: Barcelona
country: Spain
facility: Theravance Biopharma Investigational Site
city: Madrid
country: Spain
facility: Theravance Biopharma Investigational Site
city: Sevilla
country: Spain
facility: Theravance Biopharma Investigational Site
city: Valencia
country: Spain
facility: Theravance Biopharma Investigational Site
city: Kaohsiung
country: Taiwan
facility: Theravance Biopharma Investigational Site
city: Taichung
country: Taiwan
facility: Theravance Biopharma Investigational Site
city: Tainan
country: Taiwan
facility: Theravance Biopharma Investigational Site
city: Taipei
country: Taiwan
facility: Theravance Biopharma Investigational Site
city: Kiev
country: Ukraine
facility: Theravance Biopharma Investigational Site
state: Kiev City
city: Kyiv
country: Ukraine
facility: Theravance Biopharma Investigational Site
state: Kiev
city: Kyiv
country: Ukraine
facility: Theravance Biopharma Investigational Site
state: Kiev
city: Kremenchuk
country: Ukraine
facility: Theravance Biopharma Investigational Site
state: Poltava
city: Úzhgorod
country: Ukraine
facility: Theravance Biopharma Investigational Site
state: Transcarpathian
city: Vinnytsia
country: Ukraine
facility: Theravance Biopharma Investigational Site
state: Vinnytsya
city: Vinnytsia
country: Ukraine
facility: Theravance Biopharma Investigational Site
state: Vinnytsya
city: Chernivtsi
country: Ukraine
facility: Theravance Biopharma Investigational Site
city: Kharkiv
country: Ukraine
facility: Theravance Biopharma Investigational Site
city: Lviv
country: Ukraine
facility: Theravance Biopharma Investigational Site #2
city: Lviv
country: Ukraine
facility: Theravance Biopharma Investigational Site
city: Ternopil
country: Ukraine
facility: Theravance Biopharma Investigational Site
city: Vinnytsia
country: Ukraine
facility: Theravance Biopharma Investigational Site
city: Vinnytsia
country: Ukraine
facility: Theravance Biopharma Investigational Site
city: Zaporizhzhya
country: Ukraine
facility: Theravance Biopharma Investigational Site
city: Zaporizhzhya
country: Ukraine
facility: Theravance Biopharma Investigational Site
city: Úzhgorod
country: Ukraine
facility: Theravance Biopharma Investigational Site
Study officials:
affiliation: Theravance Biopharma
name: Medical Monitor
role: STUDY_DIRECTOR
References: