Clinical trial NCT03464136: Safety and Efficacy of Adalimumab Versus Ustekinumab for One Year
Official title: A Phase 3b, Multicenter, Randomized, Blinded, Active-Controlled Study to Compare the Efficacy and Safety of Ustekinumab to That of Adalimumab in the Treatment of Biologic Naïve Subjects With Moderately-to-Severely Active Crohn's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Crohn Disease
Lead sponsor: Janssen Scientific Affairs, LLC
Sponsor class: INDUSTRY
First posted: 2018-03-13
Enrollment: 386
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare the efficacy of treatment with ustekinumab or adalimumab in biologic naive participants with moderately-to-severely active Crohn's disease (CD) who have previously failed or were intolerant to conventional therapy (corticosteroids and/or immunomodulators, such as azathioprine, 6-mercaptopurine, or methotrexate), as measured by clinical remission at one year.

Detailed description: This study compares the safety and efficacy of ustekinumab versus adalimumab. It will consist of screening (within 1- 5 weeks prior to Week 0), treatment phase (Weeks 0 to 52), and follow-up phase (up to Week 76). The primary hypothesis is that ustekinumab is superior to adalimumab as measured by clinical remission after one year of treatment. Study assessments will include Crohn's disease activity index (CDAI), video ileocolonoscopy; CD-related healthcare utilization; patient-reported outcomes (PROs); laboratory evaluations; biomarkers; review of concomitant medications and adverse events (AEs); and evaluation of serum concentrations of study agent as well as development of antibodies to study agent. All participants will randomly be assigned to receive either ustekinumab or adalimumab. No participants will be treated with placebo only.

Eligibility criteria: Inclusion Criteria:

* Has Crohn's Disease (CD) or fistulizing CD of at least 3 months' duration, with colitis, ileitis, or ileocolitis, confirmed at some time in the past by radiography, histology, and/or endoscopy
* Has moderately-to-severely active CD with a baseline Crohn's disease activity index (CDAI) score of greater than or equal to (\>=) 220 and less than or equal to (\<=) 450
* Has one or more ulceration on screening ileocolonoscopy (which by definition, would result in an Simple Endoscopic Score for Crohn's Disease \[SES-CD\] of at least 3)
* Has failed or was intolerant to conventional therapy (corticosteroids, azathioprine \[AZA\], 6-mercaptopurine \[6-MP\] and/or methotrexate \[MTX\]) at adequate doses or is corticosteroid dependent
* Has not previously received an approved biologic for Crohn's Disease (i.e., infliximab, adalimumab, certolizumab pegol, ustekinumab, natalizumab, vedolizumab or approved biosimilars of these agents)
* Participants on oral corticosteroids (e.g., prednisone, budesonide) at a prednisone-equivalent dose of \<=40 or milligram/day (mg/day) or \<=9 mg/day of budesonide are budesonide \<=9 mg/day are permitted if doses are stable for 3 weeks prior to baseline
* Participants on AZA, 6-MP, or MTX at screening (or recently prior), must discontinue these medications at least 3 weeks prior to baseline

Exclusion Criteria:

* Has complications of CD that are likely to require surgery or would confound the ability to assess the effect of ustekinumab or adalimumab treatment using the CDAI, such as: active stoma; short-gut syndrome and severe or symptomatic strictures or stenosis
* Currently has, or is suspected to have, an abscess. Recent cutaneous and perianal abscesses are not exclusionary if drained and adequately treated at least 3 weeks prior to baseline, or 8 weeks prior for intra-abdominal abscesses, if there is no anticipated need for any further surgery. Participants with active fistulas may be included if there is no anticipation of a need for surgery and there are currently no abscesses present
* Has had any kind of bowel resection within 6 months prior to baseline or other intra-abdominal surgery or a hospital admission for bowel obstruction within 3 months prior to baseline
* Has a stool culture or other examination positive for an enteric pathogen, including Clostridium difficile toxin, in the last 4 months unless a repeat examination is negative and there are no signs of ongoing infection with that pathogen
* Has received a Bacillus Calmette-Guerin (BCG) vaccination within 12 months or any other live bacterial or live viral vaccination within 2 weeks of baseline
* Has a history of, or ongoing, chronic or recurrent infectious disease, including but not limited to, chronic renal infection, chronic chest infection, recurrent urinary tract infection (eg, recurrent pyelonephritis or chronic nonremitting cystitis), or infected skin wounds or ulcers

Primary outcomes:
measure: Percentage of Participants With Clinical Remission at Week 52
timeFrame: Week 52
Secondary outcomes:
measure: Percentage of Participants With Corticosteroid-free Remission at Week 52
timeFrame: Week 52
measure: Percentage of Participants With Clinical Response at Week 52
timeFrame: Week 52
measure: Percentage of Participants in Patient Reported Outcome (PRO)-2 Symptom Remission at Week 52
timeFrame: Week 52
measure: Percentage of Participants With Clinical Remission at Week 16
timeFrame: Week 16
measure: Percentage of Participants With Endoscopic Remission at Week 52
timeFrame: Week 52
measure: Percentage of Participants With Clinical Remission Through Week 52
timeFrame: Weeks 2, 8, 16, 24, 32, 40, 48, and 52
measure: Percentage of Participants With Clinical Response Through Week 52
timeFrame: Weeks 2, 8, 16, 24, 32, 40, 48, and 52
measure: Percentage of Participants With Durable Clinical Response at Week 52
timeFrame: Week 52
measure: Percentage of Participants With Durable Clinical Remission at Week 52
timeFrame: Week 52
measure: Percentage of Participants With Abdominal Pain (AP) Improvement Through Week 52
timeFrame: Weeks 2, 8, 16, 24, 32, 40, 48, and 52
measure: Percentage of Participants With Reduction in Frequency of Diarrhea Through Week 52
timeFrame: Weeks 2, 8, 16, 24, 32, 40, 48, and 52
measure: Percentage of Participants With Clinical and Biomarker Remission at Weeks 8, 16 and 52
timeFrame: At Weeks 8, 16 and 52
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: Up to Week 52 and up to Week 76
measure: Percentage of Participants With Infections
timeFrame: Up to Week 52 and up to Week 76
measure: Percentage of Participants With Serious Infections
timeFrame: Up to Week 52 and up to Week 76
measure: Percentage of Participants With Serious Adverse Events (SAEs)
timeFrame: Up to Week 52 and up to Week 76
measure: Percentage of Participants With Anti-drug Antibodies
timeFrame: Up to Week 52
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Alabama Medical Group
state: Alabama
city: San Diego
country: United States
facility: Precision Research Institute
state: California
city: Colorado Springs
country: United States
facility: Peak Gastroenterology Associates
state: Colorado
city: Bridgeport
country: United States
facility: Gastro Associates of Fairfield County PC
state: Connecticut
city: Danbury
country: United States
facility: Western Connecticut Health Network/Danbury Hospital
state: Connecticut
city: Washington
country: United States
facility: Medstar Washington Hospital Center
state: District of Columbia
city: Clearwater
country: United States
facility: Gastro Florida
state: Florida
city: Gainesville
country: United States
facility: Florida Research Network, LLC
state: Florida
city: Largo
country: United States
facility: Florida Center For Gastroenterology
state: Florida
city: Maitland
country: United States
facility: Center for Advanced Gastroenterology
state: Florida
city: Naples
country: United States
facility: Gastroenterology Group Of Naples
state: Florida
city: Port Orange
country: United States
facility: Advanced Medical Research Center
state: Florida
city: Tampa
country: United States
facility: Apex Clinical Research
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Suwanee
country: United States
facility: Atlanta Gastroenterology Specialists, PC
state: Georgia
city: Idaho Falls
country: United States
facility: Grand Teton Research Group, PLLC
state: Idaho
city: Pratt
country: United States
facility: Health Science Research Center
state: Kansas
city: Crestview Hills
country: United States
facility: Tri-State Gastroenterology Assoc
state: Kentucky
city: Hazard
country: United States
facility: Gastroenterology Associates Of Hazard
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Baton Rouge
country: United States
facility: Texas Digestive Disease Consultants
state: Louisiana
city: Houma
country: United States
facility: CroNOLA, LLC
state: Louisiana
city: Shreveport
country: United States
facility: Louisiana Research Center, LLC
state: Louisiana
city: Chevy Chase
country: United States
facility: Chevy Chase Clinical Research
state: Maryland
city: Chesterfield
country: United States
facility: Clinical Research Institute of Michigan, LLC
state: Michigan
city: Ypsilanti
country: United States
facility: Huron Gastroenterology Associates Center for Digestive Care
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Saint Louis University Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Mercy Clinic East Community
state: Missouri
city: Burnt Hills
country: United States
facility: Saratoga Schenectady Gastroenterology Associates
state: New York
city: Great Neck
country: United States
facility: NYU Langone Long Island Clinical Research Associates
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Poughkeepsie
country: United States
facility: Premier Medical Group Of The Hudson Valley, Pc
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Asheville
country: United States
facility: Digestive Health Partners
state: North Carolina
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Raleigh
country: United States
facility: Duke University Hospital Medical Center
state: North Carolina
city: Wilmington
country: United States
facility: Wilmington Gastroenterology Associates
state: North Carolina
city: Fargo
country: United States
facility: Fargo Gastroenterology Clinic, PC
state: North Dakota
city: Beachwood
country: United States
facility: Northshore Gastroenterology Research, LLC
state: Ohio
city: Cincinnati
country: United States
facility: TriHealth Digestive Institute
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Hospital
state: Ohio
city: Dayton
country: United States
facility: Dayton Gastroenterology, Inc
state: Ohio
city: Mentor
country: United States
facility: Great Lakes Gastroenterology Research, LLC
state: Ohio
city: Oklahoma City
country: United States
facility: Digestive Disease Specialists Inc
state: Oklahoma
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny-Singer Research Institute
state: Pennsylvania
city: Greenville
country: United States
facility: Gastroenterology Associates P.A.
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Channelview
country: United States
facility: Aztec Clinical Research, Inc.
state: Texas
city: Garland
country: United States
facility: DHAT Research Institute
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: University of Texas at Houston Medical School
state: Texas
city: San Antonio
country: United States
facility: Gastroenterology Research of America, LLC
state: Texas
city: Southlake
country: United States
facility: Texas Digestive Disease Consultants
state: Texas
city: Tyler
country: United States
facility: Tyler Research Institute, LLC
state: Texas
city: Chesapeake
country: United States
facility: Gastroenterology Associates of Tidewater
state: Virginia
city: Fairfax
country: United States
facility: Verity Research, Inc
state: Virginia
city: Lynchburg
country: United States
facility: Gastroenterology Associates of Central Virginia
state: Virginia
city: Norfolk
country: United States
facility: Digestive And Liver Disease Specialists
state: Virginia
city: Richmond
country: United States
facility: McGuire VAMC
state: Virginia
city: Suffolk
country: United States
facility: Virginia Gastroenterology Institute
state: Virginia
city: Bellevue
country: United States
facility: Washington Gastroenterology, PLLC
state: Washington
city: Tacoma
country: United States
facility: Washington Gastroenterology, PLLC
state: Washington
city: Clayton
country: Australia
facility: Monash Health, Monash Medical Centre
city: Melbourne
country: Australia
facility: Alfred Hospital
city: South Brisbane
country: Australia
facility: Mater Hospital Brisbane Inflammatory Bowel Diseases
city: Subiaco
country: Australia
facility: St John of God Subiaco Hospital
city: Woodville South
country: Australia
facility: The Queen Elizabeth Hospital
city: Gent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: UZ Leuven
city: Tournai
country: Belgium
facility: CHwapi
city: Belo Horizonte - MG
country: Brazil
facility: Hospital Das Clinicas Da Ufmg
city: Goiania
country: Brazil
facility: Inst Goiano Gastroenterologia e Endoscopia Digest Ltda - Clinica de Gastro
city: Juiz de Fora
country: Brazil
facility: Endogastro Clínica de Gastroenterologia e Endoscopia Digestiva Lida
city: Porto Alegre
country: Brazil
facility: Hospital das Clinicas de Porto Alegre
city: Ribeirao Preto
country: Brazil
facility: Hospital Das Clinicas Da Faculdade De Medicina De RPUSP HCRP
city: Rio de Janeiro
country: Brazil
facility: Universidade Federal do Rio de Janeiro - Faculdade de Medicina
city: Rio de Janeiro
country: Brazil
facility: Hospital Copa D'Or
city: Santo Andre
country: Brazil
facility: Fundacao do ABC Centro Universitario FMABC
city: Pleven
country: Bulgaria
facility: UMHAT 'Dr. Georgi Stranski', EAD
city: Rousse
country: Bulgaria
facility: MHAT Rousse
city: Sofia
country: Bulgaria
facility: 2-nd MHAT
city: Varna
country: Bulgaria
facility: Diagnostic Consulting Center Mladost - M Varna
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Hamilton
country: Canada
facility: McMaster University
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Greenfield Park
country: Canada
facility: CISSS de la Monteregie Centre
state: Quebec
city: Mont-Royal
country: Canada
facility: CMIIM, Centre médical L'Enjeu
state: Quebec
city: Brno
country: Czechia
facility: Fakultní nemocnice u sv. Anny v Brn
city: Horovice
country: Czechia
facility: Nemocnice Horovice, a.s.
city: Hradec Kralove
country: Czechia
facility: Hepato-gastroenterologie HK, s.r.o.
city: Praha 10
country: Czechia
facility: Fakultni nemocnice Kralovske Vinohrady
city: Praha 9
country: Czechia
facility: ISCARE a.s.
city: Amiens
country: France
facility: CHU Amiens
city: Montpellier
country: France
facility: CHRU Montpellier - Hopital Saint-Eloi
city: Nantes
country: France
facility: Hotel Dieu
city: Paris
country: France
facility: Hopital Saint Louis
city: Saint Priest en jarez
country: France
facility: CHU Saint Etienne
city: Toulouse
country: France
facility: Clinique Ambroise Pare
city: Freiburg
country: Germany
facility: Universitatsklinikum Freiburg
city: Hamburg
country: Germany
facility: Asklepios Westklinikum
city: Heidelberg
country: Germany
facility: Uniklinikum Heidelberg
city: Muenster
country: Germany
facility: MVZ Portal10
city: Budapest
country: Hungary
facility: Magyar Honvedseg Egeszsegugyi Kozpont
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Békéscsaba
country: Hungary
facility: Réthy Pál Kórház - Rendelőintézet
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont
city: Miskolc
country: Hungary
facility: Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz
city: Szombathely
country: Hungary
facility: Markusovszky Egyetemi Oktatokorhaz
city: Bologna
country: Italy
facility: Policlinico Sant'Orsola Malpighi
city: Messina
country: Italy
facility: AOU Policlinico G.Martino
city: Milano
country: Italy
facility: ASST Fatebenefratelli Sacco
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova
city: Palermo
country: Italy
facility: Ospedale Villa Sofia-Cervello
city: RHO
country: Italy
facility: Azienda Ospedaliera G.Salvini Ospedale di Rho
city: Roma
country: Italy
facility: Azienda Ospedaliera Universitaria 'Policlinico Tor Vergata'
city: Roma
country: Italy
facility: Azienda Complesso Ospedaliero San Filippo Neri
city: Roma
country: Italy
facility: Fondazione Policlinico Gemelli Università Cattolica
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
city: Torino
country: Italy
facility: AO Ordine Mauriziano
city: Daegu
country: Korea, Republic of
facility: Yeungnam University Hospital
city: Gyeonggi-do
country: Korea, Republic of
facility: The Catholic university of Korea, St. Vincent's Hospital
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
city: Amsterdam
country: Netherlands
facility: VUMC Amsterdam
city: Arnhem
country: Netherlands
facility: Rijnstate Ziekenhuis
city: Groningen
country: Netherlands
facility: UMCG
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Nijmegen
country: Netherlands
facility: Radboudumc
city: Rotterdam
country: Netherlands
facility: Sint Franciscus Gasthuis
city: Rotterdam
country: Netherlands
facility: Ikazia Ziekenhuis
city: Bialystok
country: Poland
facility: Gastromed Kralisz Romatowski Stachurska Sp. j.
city: Gdansk
country: Poland
facility: Synexus Polska Sp z o o
city: Krakow
country: Poland
facility: Centrum Medyczne Plejady
city: Krakow
country: Poland
facility: Centrum Medyczne Pratia Poznan
city: Lodz
country: Poland
facility: Uniwersytecki Szpital Kliniczny nr 1 im. N. Barlickiego
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie Oddzial Gastroenterologii
city: Rzeszow
country: Poland
facility: Centrum Medyczne Medyk
city: Sopot
country: Poland
facility: Endoskopia Sp z o o z siedziba w Sopocie
city: Warsaw
country: Poland
facility: Centralny Szpital Kliniczny MSWiA w Warszawie
city: Warszawa
country: Poland
facility: Niepubliczny Zaklad Opieki Zdrowotnej Vivamed Jadwiga Miecz
city: Warszawa
country: Poland
facility: Gabinety Lekarskie Bodyclinic
city: Wroclaw
country: Poland
facility: Melita Medical Sp. z o.o.
city: Zamosc
country: Poland
facility: ETG Zamosc
city: Ekaterinburg
country: Russian Federation
facility: OOO MO New Hospital
city: Irkutsk
country: Russian Federation
facility: Irkutsk State Medical Academy of Postgraduate Education
city: Moscva
country: Russian Federation
facility: GU Moscow Regional Research Clinical Institute n.a. M.F.Vla
city: Rostov-On-Don
country: Russian Federation
facility: Rostov State Medical University
city: Saint Petersburg
country: Russian Federation
facility: Elizavetinskaya hospital
city: Saint Petersburg
country: Russian Federation
facility: City Clinical Hospital #31
city: Ufa
country: Russian Federation
facility: GBUZ Respublican Clinical Hospital n.a. GG Kuvatova
city: Ufa
country: Russian Federation
facility: City Clinical Hospital # 21
city: Belgrade
country: Serbia
facility: Clinical Hospital Center Zemun
city: Belgrade
country: Serbia
facility: Clinical Hospital Center Zvezdara
city: Kragujevac
country: Serbia
facility: University Clinical Center Kragujevac
city: Nis
country: Serbia
facility: University Clinical Center NIS
city: Vojvodina
country: Serbia
facility: Clinical Center of Vojvodina
city: Zemun
country: Serbia
facility: Clinical Hospital Center Bezanijska Kosa
city: Barcelona
country: Spain
facility: Hosp. Del Mar
city: Barcelona
country: Spain
facility: Hosp. de La Santa Creu I Sant Pau
city: Girona
country: Spain
facility: Hosp. Univ. Dr. Josep Trueta
city: Oviedo
country: Spain
facility: Hosp. Univ. Central de Asturias
city: Sabadell
country: Spain
facility: Corporacio Sanitari Parc Tauli
city: Salamanca
country: Spain
facility: Hosp Clinico Univ de Salamanca
city: Santander
country: Spain
facility: Hosp. Univ. Marques de Valdecilla
city: Sevilla
country: Spain
facility: Hosp. Virgen Macarena
city: Valladolid
country: Spain
facility: Hosp. Univ. Rio Hortega
city: Zaragoza
country: Spain
facility: Hosp. Univ. Miguel Servet
city: Bath
country: United Kingdom
facility: Royal United Hospital
city: Bury
country: United Kingdom
facility: Pennine Acute Hospitals-Fairfield General Hospital
city: Kingston upon Thames
country: United Kingdom
facility: Kingston Hospital
city: London
country: United Kingdom
facility: Guy's and St Thomas' Hospital
city: London
country: United Kingdom
facility: St George's Hospital
city: Southampton
country: United Kingdom
facility: Southampton University Hospitals NHS Trust
city: Taunton
country: United Kingdom
facility: Musgrove Park Hospital
Study officials:
affiliation: Janssen Scientific Affairs, LLC
name: Janssen Scientific Affairs, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Sands BE, Irving PM, Hoops T, Izanec JL, Gao LL, Gasink C, Greenspan A, Allez M, Danese S, Hanauer SB, Jairath V, Kuehbacher T, Lewis JD, Loftus EV Jr, Mihaly E, Panaccione R, Scherl E, Shchukina OB, Sandborn WJ; SEAVUE Study Group. Ustekinumab versus adalimumab for induction and maintenance therapy in biologic-naive patients with moderately to severely active Crohn's disease: a multicentre, randomised, double-blind, parallel-group, phase 3b trial. Lancet. 2022 Jun 11;399(10342):2200-2211. doi: 10.1016/S0140-6736(22)00688-2.