Safety and Efficacy of Adalimumab Versus Ustekinumab for One Year

NCT ID: NCT03464136

Last Updated: 2025-04-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 386 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-29
• Study Completion Date: 2021-05-21

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.

Conditions

Crohn Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Group 1 (Ustekinumab)

Participants will receive intravenous (IV) infusion of ustekinumab (approximately 6 milligram/kilogram \[mg/kg\]) and 4 subcutaneous (SC) injections of placebo for adalimumab at Week 0, followed by 2 SC injections of placebo at Week 2. From Week 4 to Week 56, participants will self-administer one SC injection of ustekinumab 90 milligram (mg) every 8 weeks (q8w) starting at Week 8 and placebo adalimumab at the other designated every 2 weeks (q2w) dosing intervals.

Group Type: EXPERIMENTAL

Placebo for Ustekinumab

Intervention Type: BIOLOGICAL

Participants will receive placebo as SC injection to blind adalimumab.

Ustekinumab (6 mg/kg)

Intervention Type: BIOLOGICAL

Participants will receive ustekinumab 6 mg/kg (weight based dosing) as IV infusion.

Ustekinumab (90 mg)

Intervention Type: BIOLOGICAL

Participants will self-administer SC injection of ustekinumab 90 mg.

Group 2 (Adalimumab)

Participants will receive IV infusion of placebo for ustekinumab and 4 SC injections of adalimumab (each 40 mg, total dose 160 mg) at Week 0, followed by 2 SC injections of adalimumab (each 40 mg, total dose 80 mg) at Week 2. From Week 4 to Week 56, participants will self-administer 1 SC injection of adalimumab 40 mg q2w.

Group Type: ACTIVE_COMPARATOR

Placebo for Adalimumab

Intervention Type: BIOLOGICAL

Participants will receive placebo as IV infusion to blind ustekinumab.

Adalimumab (40 mg)

Intervention Type: BIOLOGICAL

Participants will self-administer multiple SC injections of adalimumab (each 40 mg) and will receive total dose of 160 mg at Week 0, 80 mg at Week 2, and 40 mg q2w from Week 4 to 56.

Interventions

Placebo for Ustekinumab

Participants will receive placebo as SC injection to blind adalimumab.

Intervention Type: BIOLOGICAL

Placebo for Adalimumab

Participants will receive placebo as IV infusion to blind ustekinumab.

Intervention Type: BIOLOGICAL

Ustekinumab (6 mg/kg)

Participants will receive ustekinumab 6 mg/kg (weight based dosing) as IV infusion.

Intervention Type: BIOLOGICAL

Ustekinumab (90 mg)

Participants will self-administer SC injection of ustekinumab 90 mg.

Intervention Type: BIOLOGICAL

Adalimumab (40 mg)

Participants will self-administer multiple SC injections of adalimumab (each 40 mg) and will receive total dose of 160 mg at Week 0, 80 mg at Week 2, and 40 mg q2w from Week 4 to 56.

Intervention Type: BIOLOGICAL

Other Intervention Names

Stelara; Stelara; Humira

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Scientific Affairs, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Scientific Affairs, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Scientific Affairs, LLC

Locations

Alabama Medical Group

Mobile, Alabama, United States

Precision Research Institute

San Diego, California, United States

Peak Gastroenterology Associates

Colorado Springs, Colorado, United States

Gastro Associates of Fairfield County PC

Bridgeport, Connecticut, United States

Western Connecticut Health Network/Danbury Hospital

Danbury, Connecticut, United States

Medstar Washington Hospital Center

Washington D.C., District of Columbia, United States

Gastro Florida

Clearwater, Florida, United States

Florida Research Network, LLC

Gainesville, Florida, United States

Florida Center For Gastroenterology

Largo, Florida, United States

Center for Advanced Gastroenterology

Maitland, Florida, United States

Gastroenterology Group Of Naples

Naples, Florida, United States

Advanced Medical Research Center

Port Orange, Florida, United States

Apex Clinical Research

Tampa, Florida, United States

Cleveland Clinic Florida

Weston, Florida, United States

Atlanta Gastroenterology Specialists, PC

Suwanee, Georgia, United States

Grand Teton Research Group, PLLC

Idaho Falls, Idaho, United States

Health Science Research Center

Pratt, Kansas, United States

Tri-State Gastroenterology Assoc

Crestview Hills, Kentucky, United States

Gastroenterology Associates Of Hazard

Hazard, Kentucky, United States

University of Louisville

Louisville, Kentucky, United States

Texas Digestive Disease Consultants

Baton Rouge, Louisiana, United States

CroNOLA, LLC

Houma, Louisiana, United States

Louisiana Research Center, LLC

Shreveport, Louisiana, United States

Chevy Chase Clinical Research

Chevy Chase, Maryland, United States

Clinical Research Institute of Michigan, LLC

Chesterfield, Michigan, United States

Huron Gastroenterology Associates Center for Digestive Care

Ypsilanti, Michigan, United States

Mayo Clinic

Rochester, Minnesota, United States

Saint Louis University Hospital

St Louis, Missouri, United States

Mercy Clinic East Community

St Louis, Missouri, United States

Saratoga Schenectady Gastroenterology Associates

Burnt Hills, New York, United States

NYU Langone Long Island Clinical Research Associates

Great Neck, New York, United States

Weill Cornell Medical College

New York, New York, United States

Mount Sinai School of Medicine

New York, New York, United States

Columbia University Medical Center

New York, New York, United States

Premier Medical Group Of The Hudson Valley, Pc

Poughkeepsie, New York, United States

University of Rochester Medical Center

Rochester, New York, United States

Digestive Health Partners

Asheville, North Carolina, United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Duke University Hospital Medical Center

Raleigh, North Carolina, United States

Wilmington Gastroenterology Associates

Wilmington, North Carolina, United States

Fargo Gastroenterology Clinic, PC

Fargo, North Dakota, United States

Northshore Gastroenterology Research, LLC

Beachwood, Ohio, United States

TriHealth Digestive Institute

Cincinnati, Ohio, United States

University Hospitals Case Medical Center

Cleveland, Ohio, United States

Ohio State University Hospital

Columbus, Ohio, United States

Dayton Gastroenterology, Inc

Dayton, Ohio, United States

Great Lakes Gastroenterology Research, LLC

Mentor, Ohio, United States

Digestive Disease Specialists Inc

Oklahoma City, Oklahoma, United States

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Allegheny-Singer Research Institute

Pittsburgh, Pennsylvania, United States

Gastroenterology Associates P.A.

Greenville, South Carolina, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Aztec Clinical Research, Inc.

Channelview, Texas, United States

DHAT Research Institute

Garland, Texas, United States

Baylor College of Medicine

Houston, Texas, United States

University of Texas at Houston Medical School

Houston, Texas, United States

Gastroenterology Research of America, LLC

San Antonio, Texas, United States

Texas Digestive Disease Consultants

Southlake, Texas, United States

Tyler Research Institute, LLC

Tyler, Texas, United States

Gastroenterology Associates of Tidewater

Chesapeake, Virginia, United States

Verity Research, Inc

Fairfax, Virginia, United States

Gastroenterology Associates of Central Virginia

Lynchburg, Virginia, United States

Digestive And Liver Disease Specialists

Norfolk, Virginia, United States

McGuire VAMC

Richmond, Virginia, United States

Virginia Gastroenterology Institute

Suffolk, Virginia, United States

Washington Gastroenterology, PLLC

Bellevue, Washington, United States

Washington Gastroenterology, PLLC

Tacoma, Washington, United States

Monash Health, Monash Medical Centre

Clayton, , Australia

Alfred Hospital

Melbourne, , Australia

Mater Hospital Brisbane Inflammatory Bowel Diseases

South Brisbane, , Australia

St John of God Subiaco Hospital

Subiaco, , Australia

The Queen Elizabeth Hospital

Woodville South, , Australia

UZ Gent

Ghent, , Belgium

UZ Leuven

Leuven, , Belgium

CHwapi

Tournai, , Belgium

Hospital Das Clinicas Da Ufmg

Belo Horizonte - MG, , Brazil

Inst Goiano Gastroenterologia e Endoscopia Digest Ltda - Clinica de Gastro

Goiânia, , Brazil

Endogastro Clínica de Gastroenterologia e Endoscopia Digestiva Lida

Juiz de Fora, , Brazil

Hospital das Clinicas de Porto Alegre

Porto Alegre, , Brazil

Hospital Das Clinicas Da Faculdade De Medicina De RPUSP HCRP

Ribeirão Preto, , Brazil

Universidade Federal do Rio de Janeiro - Faculdade de Medicina

Rio de Janeiro, , Brazil

Hospital Copa D'Or

Rio de Janeiro, , Brazil

Fundacao do ABC Centro Universitario FMABC

Santo André, , Brazil

UMHAT 'Dr. Georgi Stranski', EAD

Pleven, , Bulgaria

MHAT Rousse

Rousse, , Bulgaria

2-nd MHAT

Sofia, , Bulgaria

Diagnostic Consulting Center Mladost - M Varna

Varna, , Bulgaria

University of Calgary

Calgary, Alberta, Canada

McMaster University

Hamilton, Ontario, Canada

London Health Sciences Centre

London, Ontario, Canada

CISSS de la Monteregie Centre

Greenfield Park, Quebec, Canada

CMIIM, Centre médical L'Enjeu

Mount Royal, Quebec, Canada

Fakultní nemocnice u sv. Anny v Brn

Brno, , Czechia

Nemocnice Horovice, a.s.

Hořovice, , Czechia

Hepato-gastroenterologie HK, s.r.o.

Hradec Králové, , Czechia

Fakultni nemocnice Kralovske Vinohrady

Prague, , Czechia

ISCARE a.s.

Prague, , Czechia

CHU Amiens

Amiens, , France

CHRU Montpellier - Hopital Saint-Eloi

Montpellier, , France

Hotel Dieu

Nantes, , France

Hopital Saint Louis

Paris, , France

CHU Saint Etienne

Saint-Priest-en-Jarez, , France

Clinique Ambroise Pare

Toulouse, , France

Universitatsklinikum Freiburg

Freiburg im Breisgau, , Germany

Asklepios Westklinikum

Hamburg, , Germany

Uniklinikum Heidelberg

Heidelberg, , Germany

MVZ Portal10

Münster, , Germany

Réthy Pál Kórház - Rendelőintézet

Békéscsaba, , Hungary

Magyar Honvedseg Egeszsegugyi Kozpont

Budapest, , Hungary

Semmelweis Egyetem

Budapest, , Hungary

Debreceni Egyetem Klinikai Kozpont

Debrecen, , Hungary

Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz

Miskolc, , Hungary

Markusovszky Egyetemi Oktatokorhaz

Szombathely, , Hungary

Policlinico Sant'Orsola Malpighi

Bologna, , Italy

AOU Policlinico G.Martino

Messina, , Italy

ASST Fatebenefratelli Sacco

Milan, , Italy

Azienda Ospedaliera di Padova

Padua, , Italy

Ospedale Villa Sofia-Cervello

Palermo, , Italy

Azienda Ospedaliera G.Salvini Ospedale di Rho

Rho, , Italy

Azienda Ospedaliera Universitaria 'Policlinico Tor Vergata'

Roma, , Italy

Azienda Complesso Ospedaliero San Filippo Neri

Roma, , Italy

Fondazione Policlinico Gemelli Università Cattolica

Roma, , Italy

Istituto Clinico Humanitas

Rozzano, , Italy

AO Ordine Mauriziano

Torino, , Italy

VUMC Amsterdam

Amsterdam, , Netherlands

Rijnstate Ziekenhuis

Arnhem, , Netherlands

UMCG

Groningen, , Netherlands

Leiden University Medical Center

Leiden, , Netherlands

Radboudumc

Nijmegen, , Netherlands

Sint Franciscus Gasthuis

Rotterdam, , Netherlands

Ikazia Ziekenhuis

Rotterdam, , Netherlands

Gastromed Kralisz Romatowski Stachurska Sp. j.

Bialystok, , Poland

Synexus Polska Sp z o o

Gdansk, , Poland

Centrum Medyczne Plejady

Krakow, , Poland

Centrum Medyczne Pratia Poznan

Krakow, , Poland

Uniwersytecki Szpital Kliniczny nr 1 im. N. Barlickiego

Lodz, , Poland

Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie Oddzial Gastroenterologii

Lublin, , Poland

Centrum Medyczne Medyk

Rzeszów, , Poland

Endoskopia Sp z o o z siedziba w Sopocie

Sopot, , Poland

Centralny Szpital Kliniczny MSWiA w Warszawie

Warsaw, , Poland

Niepubliczny Zaklad Opieki Zdrowotnej Vivamed Jadwiga Miecz

Warsaw, , Poland

Gabinety Lekarskie Bodyclinic

Warsaw, , Poland

Melita Medical Sp. z o.o.

Wroclaw, , Poland

ETG Zamosc

Zamość, , Poland

Irkutsk State Medical Academy of Postgraduate Education

Irkutsk, , Russia

GU Moscow Regional Research Clinical Institute n.a. M.F.Vla

Moscva, , Russia

Rostov State Medical University

Rostov-on-Don, , Russia

Elizavetinskaya hospital

Saint Petersburg, , Russia

City Clinical Hospital #31

Saint Petersburg, , Russia

GBUZ Respublican Clinical Hospital n.a. GG Kuvatova

Ufa, , Russia

City Clinical Hospital # 21

Ufa, , Russia

OOO MO New Hospital

Yekaterinburg, , Russia

Clinical Hospital Center Zemun

Belgrade, , Serbia

Clinical Hospital Center Zvezdara

Belgrade, , Serbia

University Clinical Center Kragujevac

Kragujevac, , Serbia

University Clinical Center NIS

Niš, , Serbia

Clinical Center of Vojvodina

Vojvodina, , Serbia

Clinical Hospital Center Bezanijska Kosa

Zemun, , Serbia

Yeungnam University Hospital

Daegu, , South Korea

The Catholic university of Korea, St. Vincent's Hospital

Gyeonggi-do, , South Korea

Seoul National University Bundang Hospital

Seongnam-si, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Severance Hospital Yonsei University Health System

Seoul, , South Korea

Hosp. Del Mar

Barcelona, , Spain

Hosp. de La Santa Creu I Sant Pau

Barcelona, , Spain

Hosp. Univ. Dr. Josep Trueta

Girona, , Spain

Hosp. Univ. Central de Asturias

Oviedo, , Spain

Corporacio Sanitari Parc Tauli

Sabadell, , Spain

Hosp Clinico Univ de Salamanca

Salamanca, , Spain

Hosp. Univ. Marques de Valdecilla

Santander, , Spain

Hosp. Virgen Macarena

Seville, , Spain

Hosp. Univ. Rio Hortega

Valladolid, , Spain

Hosp. Univ. Miguel Servet

Zaragoza, , Spain

Royal United Hospital

Bath, , United Kingdom

Pennine Acute Hospitals-Fairfield General Hospital

Bury, , United Kingdom

Kingston Hospital

Kingston upon Thames, , United Kingdom

Guy's and St Thomas' Hospital

London, , United Kingdom

St George's Hospital

London, , United Kingdom

Southampton University Hospitals NHS Trust

Southampton, , United Kingdom

Musgrove Park Hospital

Taunton, , United Kingdom

Countries

United States; Australia; Belgium; Brazil; Bulgaria; Canada; Czechia; France; Germany; Hungary; Italy; Netherlands; Poland; Russia; Serbia; South Korea; Spain; United Kingdom

References

Hasskamp J, Meinhardt C, Timmer A. Anti-IL-12/23p40 antibodies for induction of remission in Crohn's disease. Cochrane Database Syst Rev. 2025 May 13;5(5):CD007572. doi: 10.1002/14651858.CD007572.pub4.

Reference Type: DERIVED

PMID: 40357993 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35691323 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2017-004209-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CNTO1275CRD3007

Identifier Type: OTHER

Identifier Source: secondary_id

CR108449

Identifier Type: -

Identifier Source: org_study_id