Efficacy & Safety of TD-1473 in Ulcerative Colitis

Ulcerative Colitis (UC) Clinical Trial

— RHEA  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03758443
• Other study ID #: 0157
• Secondary ID: 2018-002136-24
• Status: Terminated
• Phase: Phase 2/Phase 3
• Start date: March 11, 2019
• Est. completion date: October 20, 2021

Study information

• Verified date: November 2021
• Source: Theravance Biopharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 239
• Est. completion date: October 20, 2021
• Est. primary completion date: October 20, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis (UC)

Intervention

Drug:
• TD-1473 Dose A
See Arm description
• TD-1473 Dose B
See Arm description
• TD-1473 Dose C
See Arm description
• Placebo
See Arm description

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Theravance Biopharma

Countries where clinical trial is conducted

United States,  Australia,  Bulgaria,  Canada,  France,  Georgia,  Germany,  Greece,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  Poland,  Portugal,  Romania,  Serbia,  Slovakia,  South Africa,  Spain,  Taiwan,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline to Week 8
Primary	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.	mWeek 44
Secondary	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.	Week 8
Secondary	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.	Baseline to mWeek 44
Secondary	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.	mWeek 44
Secondary	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.	mWeek 44