Clinical trial NCT06227910: A Study of Vedolizumab With and Without Upadacitinib in Adults With Crohn's Disease
Official title: A Randomized, Double-Blind, Phase 3b Study to Evaluate the Short- and Long-Term Efficacy and Safety of Dual Targeted Therapy With Intravenous Vedolizumab and Oral Upadacitinib Compared With Intravenous Vedolizumab and Oral Placebo for Induction Followed by Intravenous Vedolizumab Monotherapy for Maintenance in the Treatment of Adults With Moderately to Severely Active Crohn's Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Crohn's Disease
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2024-01-29
Enrollment: 396
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The main aim of this study is to learn whether vedolizumab and upadacitinib given together (also called dual targeted therapy or DTT) reduces bowel inflammation and ulcers in the bowel compared to vedolizumab only (also called monotherapy) in adults with moderately or severely active Crohn's Disease (CD) after 12 weeks of treatment. Other aims are to learn how safe and effective DTT is compared to monotherapy for these participants.

All participants will receive DTT (either vedolizumab and upadacitinib or vedolizumab and placebo) for 12 weeks. Participants responding to the treatment will then receive vedolizumab only (monotherapy) for an additional 40 weeks.

During the study, participants will visit their study clinic 15 times.

Detailed description: The drug being tested in this study is vedolizumab. Vedolizumab is being tested to treat people with moderately to severely active CD. The study will look at the efficacy and safety of vedolizumab with and without upadacitinib. The study will enroll approximately 396 patients. Participants will be assigned in a 1:1 ratio to one of the two treatment groups in the 12-weeks Induction Phase:

* Induction Phase: Vedolizumab + Upadacitinib
* Induction Phase: Vedolizumab + Placebo

Participants who achieve a Crohn's disease activity index (CDAI) reduction of greater than or equal to (\>=)70 points from baseline at Week 12 will enter the main study Maintenance Phase (40 weeks) of the study to receive vedolizumab monotherapy. Participants will be followed for a further 18-week safety follow-up period up to Week 70.

This multi-center trial will be conducted worldwide. The overall time to participate in this study is approximately 70 weeks.

Eligibility criteria: Inclusion Criteria:

1. The participant has a diagnosis of CD established at least 3 months before screening by clinical and endoscopic evidence and corroborated by a histopathology report.
2. The participant has a confirmed diagnosis of moderately to severely active CD as assessed by CDAI of 220-450.
3. The participant has evidence of mucosal inflammation based on the SES-CD: SES-CD score (excluding the presence of narrowing component) of \>=6 (or \>=4 for participants with isolated ileal disease), as confirmed by a central reader.
4. The participant has demonstrated an inadequate response to, loss of response to, or intolerance to corticosteroids, immunomodulators, or biologic therapy.

Exclusion Criteria:

1. The participant has a current diagnosis of ulcerative colitis or indeterminate colitis.
2. The participant has infection(s) requiring treatment with IV anti-infectives within 30 days prior to baseline or oral/intramuscular anti-infectives within 14 days prior to baseline.
3. The participant has evidence of an active infection during the screening period, or clinically significant infection within 30 days prior to screening, or ongoing chronic infection.
4. The participant has a history of recurrent or disseminated (including a single episode) herpes zoster, or disseminated (including a single episode) herpes simplex.
5. The participant has any of the following ongoing known complications of CD: abscess (abdominal or peri-anal); symptomatic bowel strictures; 2 entire missing segments of the following 5 segments: terminal ileum, right colon, transverse colon, sigmoid and left colon, and rectum; fulminant colitis; toxic megacolon; or any other manifestation that might require surgery while enrolled in the study.
6. The participant has an ostomy or ileoanal pouch.
7. The participant has severe renal impairment, defined as an estimated glomerular filtration rate of \<30 milliliters per minute per 1.73 square meters (mL/min/1.73 m\^2).
8. The participant has severe (Child-Pugh C) hepatic impairment.

Primary outcomes:
measure: Percentage of Participants Achieving Clinical Remission Based on the CDAI at Week 12
timeFrame: Week 12
measure: Percentage of Participants Exhibiting an Endoscopic Response Based on Simple Endoscopic Score for CD (SES-CD) at Week 12
timeFrame: Week 12
Secondary outcomes:
measure: Percentage of Participants Achieving 2-item Patient-reported Outcome Measure (PRO2) Based Clinical Remission at Week 12
timeFrame: Week 12
measure: Percentage of Participants Achieving Endoscopic Remission Based on SES-CD at Week 12
timeFrame: Week 12
measure: Percentage of Participants Exhibiting Corticosteroid-free Clinical Remission in Participants who Were Taking Corticosteroids at Baseline Based on the CDAI at Week 12
timeFrame: Week 12
measure: Percentage of Participants Exhibiting a Clinical Response Based on the CDAI at Week 12
timeFrame: Week 12
measure: Percentage of Participants Achieving Clinical Remission Based on the CDAI at Week 52
timeFrame: Week 52
measure: Percentage of Participants Exhibiting an Endoscopic Response Based on SES-CD at Week 52
timeFrame: Week 52
measure: Percentage of Participants Achieving 2-item PRO2 Based Clinical Remission at Week 52
timeFrame: Week 52
measure: Percentage of Participants Achieving Endoscopic Remission Based on SES-CD at Week 52
timeFrame: Week 52
measure: Percentage of Participants Exhibiting Corticosteroid-free Clinical Remission in Participants who Were Taking Corticosteroids at Baseline Based on the CDAI at Week 52
timeFrame: Week 52
measure: Percentage of Participants Exhibiting a Clinical Response Based on the CDAI at Week 52
timeFrame: Week 52
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: UCSD Medical Center
state: California
city: Los Angeles
country: United States
facility: Keck Medicine Of USC - USC Healthcare Center 1
state: California
city: Colorado Springs
country: United States
facility: Peak Gastroenterology Associates
state: Colorado
city: Naples
country: United States
facility: GI PROS, Inc.
state: Florida
city: Orlando
country: United States
facility: Orlando Health Ambulatory Care Center
state: Florida
city: Tampa
country: United States
facility: USF Health Morsani Center for Advanced Healthcare
state: Florida
city: Indianapolis
country: United States
facility: Indiana University (IU) Health University Hospital
state: Indiana
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: New York
country: United States
facility: Mount Sinai Hospital - The Susan and Leonard Feinstein Inflammatory Bowel Disease (IBD) Clinical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center, New York-Presbyterian Hospital
state: New York
city: New York
country: United States
facility: Lenox Hill Hospital Northwell Health
state: New York
city: Greenville
country: United States
facility: Gastroenterology Associates
state: South Carolina
city: Rapid City
country: United States
facility: Rapid City Medical Center
state: South Dakota
city: San Antonio
country: United States
facility: Southern Star Research Institute, LLC
state: Texas
city: Tyler
country: United States
facility: Tyler Research Institute, LLC
state: Texas
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center - Montlake
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin Cancer Center - Froedtert Hospital
state: Wisconsin
city: Innsbruck
country: Austria
facility: Medical University Innsbruck
state: Tyrol
city: Wien
country: Austria
facility: Medizinische Universitaet Wien - Allgemeines Krankenhaus der Stadt Wien (AKH) - Universitaetsklinik fuer Innere Medizin III
state: Vienna
city: Linz
country: Austria
facility: Johannes Kepler Universitat Linz (JKU)
city: Salzburg
country: Austria
facility: Landeskrankenhaus Salzburg, Innere Medizin I, Labor im Erdgeschoss
city: Wien
country: Austria
facility: Krankenhaus der Barmherzigen Brueder Wien
city: Brussel
country: Belgium
facility: Hopital Universitaire de Bruxelles/ Academisch Ziekenhuis Brussel
state: Anderlecht
city: Bonheiden
country: Belgium
facility: Imelda GI Clinical Research Center
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Leuven
country: Belgium
facility: University Hospitals Leuven
city: Liege
country: Belgium
facility: Centre Hospitalier Chretien MontLegia
city: Curitiba
country: Brazil
facility: Hospital Universitario Cajuru
state: Parana
city: Botucatu
country: Brazil
facility: Faculdade de Medicina de Botucatu
state: Sao Paulo
city: Jau
country: Brazil
facility: Centro de Estudos Clinico do Interior Paulista - CECIP
state: Sao Paulo
city: Santo Andre
country: Brazil
facility: Pesquisare Saude
state: Sao Paulo
city: Rio De Janeiro
country: Brazil
facility: Universidade Federal do Rio de Janeiro (UFRJ)-Hospital Universitario Clementino Fraga Filho (HUCFF)
city: Sao Paulo
country: Brazil
facility: Hospital das Clinicas of the University of Sao Paulo (Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HC/FMUSP))
city: Sao Paulo
country: Brazil
facility: Unidade de Pesquisa Clinica UPC Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo
city: Calgary
country: Canada
facility: Heritage Medical Research Clinic - University Of Calgary
state: Alberta
city: Winnipeg
country: Canada
facility: University of Manitoba-Winnipeg Regional Health Authority-Health Sciences Centre
state: Manitoba
city: Halifax
country: Canada
facility: Dalhousie University
state: Nova Scotia
city: Barrie
country: Canada
facility: Barrie GI Associates
state: Ontario
city: Hamilton
country: Canada
facility: McMaster University - Farncombe Family Digestive Health Research Institute (FFDHRI)
state: Ontario
city: Oshawa
country: Canada
facility: Taunton Surgical Centre-Oshawa Clinic
state: Ontario
city: Toronto
country: Canada
facility: Toronto Immune and Digestive Health Institute (TIDHI)
state: Ontario
city: Vaughan
country: Canada
facility: Toronto Digestive Disease Associates
state: Ontario
city: Montreal
country: Canada
facility: Centre Hospitalier de l'Universite de Montreal
state: Quebec
city: Osijek
country: Croatia
facility: Poliklinika Borzan d.o.o.
city: Rijeka
country: Croatia
facility: Clinical Hospital Center Rijeka
city: Zagreb
country: Croatia
facility: University Hospital Centre Sestre Milosrdnice
city: Ceske Budejovice
country: Czechia
facility: Nemocnice Ceske Budejovice, a.s.
city: Hradec Kralove
country: Czechia
facility: Fakultni Nemocnice Hradec Kralove
city: Hradec Kralove
country: Czechia
facility: Hepato-Gastroenterologie HK, s.r.o.
city: Prague
country: Czechia
facility: IBD Clinical and Research centre
city: Aalborg
country: Denmark
facility: Aalborg Hospital
city: Hvidovre
country: Denmark
facility: Hvidovre Hospital Medicinsk Gastroenterologisk Afdeling
city: Amiens Cedex 01
country: France
facility: CHU d'Amiens-Picardie - Hopital SUD
city: Lille Cedex
country: France
facility: Hopital Huriez - CHRU de Lille
city: Marseille Cedex 20
country: France
facility: Chu - Hopital Nord
city: Nantes
country: France
facility: Centre Hospitalier Universitaire de Nantes (CHU de Nantes) - Hopital Hotel Dieu
city: Pessac
country: France
facility: Centre Hospitalier Universitaire de Bordeaux - Hopital Haut-Leveque
city: Saint Etienne
country: France
facility: CHU St Etienne Hopital Nord
city: Toulouse cedex 09
country: France
facility: Centre Hospitalier Universitaire (CHU) de Toulouse - Hopital Rangueil
city: Vandoeuvre les Nancy
country: France
facility: Centre Hospitalier Regional Universitaire de Nancy, Hopital Brabois
city: Berlin
country: Germany
facility: Krankenhaus Waldfriede e.V.
city: Frankfurt Am Main
country: Germany
facility: Agaplesion Markus Krankenhaus
city: Halle
country: Germany
facility: Studiengesellschaft BSF
city: Jena
country: Germany
facility: Universitaetsklinikum Jena
city: Kiel
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein, UKSH-Campus Kiel
city: Ludwigshafen
country: Germany
facility: St. Marien- und St. Annastiftskrankenhaus
city: Mannheim
country: Germany
facility: Universitaetsklinikum Mannheim (Umm) - Ii Medizinische Klinik
city: Athens
country: Greece
facility: University of Athens School of Medicine, Alexandra General Hospital
state: Attiki
city: Piraeus
country: Greece
facility: Metaxa Cancer Hospital
state: Attiki
city: Heraklion
country: Greece
facility: University Hospital of Heraklion
state: Crete
city: Budapest
country: Hungary
facility: Central Hospital of Northern Pest - Military Hospital
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem Altalanos Orvostudomanyi Kar Szent-Gyorgyi Albert Klinikai Kozpont, I.Sz. Belogyaszati Klinika
city: Dublin
country: Ireland
facility: Adelaide, Meath and National Children's Hospital
city: Dublin
country: Ireland
facility: University College Dublin (UCD) - St. Vincent's University Hospital (SVUH)
city: Dublin
country: Ireland
facility: Beaumont Hospital
city: Be'er Sheva
country: Israel
facility: Soroka Medical Center
city: Haifa
country: Israel
facility: Rambam Health Care Campus (RHCC)
city: Kfar-Saba
country: Israel
facility: Meir Medical Center
city: Petach Tikva
country: Israel
facility: Rabin Medical Center - Beilinson Campus (Beilinson and Hasharon Hospital)
city: Tel-Aviv
country: Israel
facility: The Tel Aviv Sourasky Medical Center
city: Milano
country: Italy
facility: Ospedale San Raffaele (HSR) Instituto Scientifico Universitario San Raffaele
city: Naples
country: Italy
facility: Azienda Ospedaliero Universitaria Federico II di Napoli
city: Roma
country: Italy
facility: A. Gemelli University Hospital, Catholic University of the Sacred Heart
city: Rozzano
country: Italy
facility: Humanitas Clinical And Research Institute
city: San Giovanni Rotondo
country: Italy
facility: Fondazione IRCSS Casa Sollievo Della Sofferenza
city: Torino
country: Italy
facility: AO Ordine Mauriziano di Torino
city: Busan
country: Korea, Republic of
facility: Inje University Haeundae Paik Hospital
city: Daegu
country: Korea, Republic of
facility: Yeungnam University Medical Center
city: Daejeon
country: Korea, Republic of
facility: The Catholic University of Korea, Daejeon St.Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Kyung Hee University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Chung-Ang University Hospital
city: Suwon-si
country: Korea, Republic of
facility: The Catholic University Of Korea, St. Vincent's Hospital
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC Research BV
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum
city: Tilburg
country: Netherlands
facility: Elisabeth TweeSteden Ziekenhuis (ETZ)
city: Drammen
country: Norway
facility: Vestre Viken HF - Baerum Sykehus
state: Gjettum
city: Bergen
country: Norway
facility: Haukeland Universitetssjukehus (Haukeland University Hospital)
city: Lorenskog
country: Norway
facility: Akershus University Hospital
city: Oslo
country: Norway
facility: Oslo Universitetssykehus HF, Ulleval
city: Lodz
country: Poland
facility: Oddzial Kliniczny Gastroenterologii Ogolnej i Onkologicznej SPZOZ Uniwersytecki Szpital Kliniczny Nr 1 im. Barlickiego Uniwersytetu Medycznego w Lodzi
city: Poznan
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny Im. H. Swiecickiego Um
city: Tychy
country: Poland
facility: H-T. Centrum Medyczne Sp. z o.o. Sp.k.
city: Warsaw
country: Poland
facility: WIP Warsaw IBD Point Profesor Kierkus
city: Warszawa
country: Poland
facility: Panstwowy Instytut Medyczny MSWiA
city: Coimbra
country: Portugal
facility: Unidade Local de Saude Coimbra
city: Lisboa
country: Portugal
facility: Centro Hospitalar Universitario Lisboa Norte EPE
city: Lisbon
country: Portugal
facility: Centro Hospitalar de Lisboa ocidental (CHLO), Hospital Egas Moniz
city: Ljubljana
country: Slovenia
facility: University Clinical Centre - Ljubljana
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon (HGUGM)
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Palma
country: Spain
facility: Hospital Universitari Son Espases
city: Pamplona
country: Spain
facility: Complejo Hospitalario de Navarra (CHN)
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario De Santiago De Compostela
city: Valencia
country: Spain
facility: Hospital Universitari I Politecnic La Fe
city: Linkoping
country: Sweden
facility: Universitetssjukhuset i Linkoping, Endokrin- och magtarmmedicinska Kliniken (EM-Kliniken)
city: Stockholm
country: Sweden
facility: Ersta sjukhus
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset - Hjartkliniken i Solna - Karolinska University Hospital
city: Stockholm
country: Sweden
facility: Danderyds Sjukhus AB
city: Basel
country: Switzerland
facility: University Hospital Basel
city: Bern
country: Switzerland
facility: University Hospital Bern (Inselspital)
city: Zurich
country: Switzerland
facility: Zentrum fur Gastroenterologie
city: Zurich
country: Switzerland
facility: Universitatsspital Zurich
city: Changhua City
country: Taiwan
facility: Changhua Christian Hospital
city: Taichung
country: Taiwan
facility: Chung Shan Medical University Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Defense Medical Center (NDMC) (Tri-Service General Hospital (TSGH)) - Neihu
city: Taoyuan City
country: Taiwan
facility: Chang Gung Memorial Foundation Linkou Chang Gung Memorial Hospital
city: London
country: United Kingdom
facility: St Thomas' Hospital - Guy's & St Thomas' NHS Foundation Trust
state: England
city: London
country: United Kingdom
facility: The Royal London Hospital - Barts Health NHS Trust
state: Greater London
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
state: Lothian
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth University Hospital - NHS Greater Glasgow & Clyde - South Glasgow University Hospital Division
state: Scotland
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: