Clinical trial NCT02065570: Study to Evaluate Efficacy and Safety of Two Drug Regimens in Subjects With Moderate to Severe Crohn's Disease
Official title: A Multicenter, Randomized, Double-Blind Study to Evaluate Higher Versus Standard Adalimumab Dosing Regimens for Induction and Maintenance Therapy in Subjects With Moderately to Severely Active Crohn's Disease and Evidence of Mucosal Ulceration
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Crohn's Disease
Keywords: Crohn's Disease
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2014-02-19
Enrollment: 514
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate higher versus standard adalimumab dosing regimens for induction and maintenance therapy in subjects with moderately to severely active Crohn's Disease and evidence of mucosal ulceration.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of Crohn's disease (CD) for at least 90 days, confirmed by endoscopy during the Screening Period.
* Active CD with a Crohn's Disease Activity Index (CDAI) despite treatment with oral corticosteroids and/or immunosuppressants.
* Mucosal ulceration on endoscopy.

Exclusion Criteria:

* Subject with ulcerative colitis or indeterminate colitis.
* Subject who has had surgical bowel resections in the past 6 months or is planning resection.
* Subjects with an ostomy or ileoanal pouch.
* Subject with symptomatic bowel stricture or abdominal or peri-anal abcess.
* Subject who has short bowel syndrome.
* Chronic recurring infections or active Tuberculosis (TB).

Primary outcomes:
measure: Percentage of Participants Who Achieved Clinical Remission at Week 4
timeFrame: Week 4
measure: Percentage of Participants With Endoscopic Response at Week 12
timeFrame: Week 12
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From first dose of study drug until 70 days following last dose of study drug in the induction study (up to 12 weeks) or maintenance study (up to 56 weeks).
Secondary outcomes:
measure: Percentage of Participants With Sustained Clinical Remission (Per CDAI) at Both Weeks 4 and 12
timeFrame: Week 4 and Week 12
measure: Percentage of Participants Who Achieve Clinical Response at Week 4 and Endoscopic Response at Week 12
timeFrame: Week 12
measure: Percentage of Participants With Clinical Remission at Week 12
timeFrame: Week 12
measure: Percentage of Participants Who Discontinued Corticosteroid Use and Achieved Clinical Remission at Week 12 Among Participants Taking Corticosteroids at Baseline
timeFrame: Week 12
measure: Percentage of Participants With Endoscopic Remission at Week 12
timeFrame: Week 12
measure: Change From Baseline in Fecal Calprotectin Level at Week 4
timeFrame: Baseline, Week 4
measure: Percentage of Participants With Hs-CRP < 5 mg/L and Fecal Calprotectin < 250 µg/g at Week 4
timeFrame: Week 4
measure: Percentage of Participants With Clinical Remission, Hs-CRP < 5 mg/L and Fecal Calprotectin < 250 µg/g at Week 4
timeFrame: Week 4
measure: Percentage of Participants With Clinical Remission, Hs-CRP < 5 mg/L and Fecal Calprotectin < 250 µg/g and Endoscopic Remission at Week 12
timeFrame: Week 12
measure: Percentage of Participants Who Achieved an SES-CD ≤ 2 at Week 12
timeFrame: Week 12
measure: Percentage of Participants With Clinical Response at Week 4
timeFrame: Week 4
measure: Percentage of Participants With Clinical Response at Week 12
timeFrame: Week 12
measure: Percentage of Participants Achieving Response in Inflammatory Bowel Disease Questionnaire (IBDQ) Bowel Symptom Domain at Week 4
timeFrame: Week 4
measure: Percentage of Participants Achieving Response in IBDQ Bowel Symptom Domain at Week 12
timeFrame: Week 12
measure: Percentage of Participants Achieving Response in IBDQ Fatigue Item at Week 12
timeFrame: Week 12
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Birmingham Gastroenterology Associates O.C /ID# 137282
state: Alabama
city: Dothan
country: United States
facility: Digestive Health Specialists of the Southeast /ID# 122483
state: Alabama
city: La Jolla
country: United States
facility: Moore UC San Diego Cancer Center /ID# 119053
state: California
city: Los Angeles
country: United States
facility: Axis Clinical Trials /ID# 130390
state: California
city: Wheat Ridge
country: United States
facility: Rocky Mountain Gastroenterology /ID# 119038
state: Colorado
city: Hamden
country: United States
facility: Medical Research Ctr CT /ID# 119037
state: Connecticut
city: Naples
country: United States
facility: Gastroenterology Group Naples /ID# 122493
state: Florida
city: Orlando
country: United States
facility: Internal Med Specialists /ID# 137737
state: Florida
city: Winter Park
country: United States
facility: Shafran Gastroenterology Ctr /ID# 119057
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University /ID# 136851
state: Georgia
city: Atlanta
country: United States
facility: Atlanta Gastro Assoc /ID# 119065
state: Georgia
city: Macon
country: United States
facility: Gastroenterology Associates of Central Georgia, LLC /ID# 119056
state: Georgia
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine /ID# 119043
state: Illinois
city: Chicago
country: United States
facility: University of Chicago DCAM /ID# 119077
state: Illinois
city: Urbana
country: United States
facility: Carle Foundation Hospital Digestive Health Research Center /ID# 136008
state: Illinois
city: Shreveport
country: United States
facility: Louisana Research Center, LLC /ID# 136749
state: Louisiana
city: Annapolis
country: United States
facility: Investigative Clinical Research /ID# 119033
state: Maryland
city: Chevy Chase
country: United States
facility: MGG Group Co, Inc.Chevy Chase Clinical Research /ID# 119042
state: Maryland
city: Brockton
country: United States
facility: Commonwealth Clinical Studies /ID# 136850
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Health Systems /ID# 119076
state: Michigan
city: Plymouth
country: United States
facility: Minnesota Gastroenterology, P. A. /ID# 137280
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic /ID# 122489
state: Minnesota
city: Kansas City
country: United States
facility: Kansas City Research Institute /ID# 119034
state: Missouri
city: Mexico
country: United States
facility: Ctr for Digest and Liver Dis /ID# 119040
state: Missouri
city: Albany
country: United States
facility: Albany Medical College /ID# 140200
state: New York
city: Great Neck
country: United States
facility: NYU Langone Long Island Clinical Research Associates /ID# 119035
state: New York
city: New York
country: United States
facility: The Mount Sinai Hospital /ID# 127116
state: New York
city: Charlotte
country: United States
facility: Charlotte Gastroenterology and Hepatology, PLLC /ID# 119041
state: North Carolina
city: Raleigh
country: United States
facility: Wake Research Associates, LLC /ID# 119029
state: North Carolina
city: Cincinnati
country: United States
facility: Consultants for Clinical Res /ID# 119052
state: Ohio
city: Tulsa
country: United States
facility: Gastro United of Tulsa /ID# 122485
state: Oklahoma
city: Portland
country: United States
facility: The Oregon Clinic, Gastroenterology - West /ID# 135272
state: Oregon
city: Warwick
country: United States
facility: West Bay Clinical Research /ID# 138330
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina /ID# 138122
state: South Carolina
city: Chattanooga
country: United States
facility: Erlanger Institute for Clinical Research /ID# 129008
state: Tennessee
city: Germantown
country: United States
facility: Gastro One /ID# 119068
state: Tennessee
city: Nashville
country: United States
facility: Nashville Med Res Inst /ID# 119050
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Univ Med Ctr /ID# 125501
state: Tennessee
city: Dallas
country: United States
facility: Texas Digestive Disease Consultants - Dallas /ID# 138121
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine /ID# 137277
state: Texas
city: Pflugerville
country: United States
facility: Austin Institute for Clinical Research /ID# 125500
state: Texas
city: Southlake
country: United States
facility: Texas Digestive Disease Consultants - Southlake /ID# 137283
state: Texas
city: Ogden
country: United States
facility: Advanced Research Institute /ID# 119048
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah /ID# 119062
state: Utah
city: Chesapeake
country: United States
facility: Gastro Assoc of Tidewater /ID# 135897
state: Virginia
city: Christiansburg
country: United States
facility: New River Valley Research Inst /ID# 127807
state: Virginia
city: Milwaukee
country: United States
facility: Wisconsin Center for Advanced Research, a division of GI Associates, LLC /ID# 119036
state: Wisconsin
city: Milwaukee
country: United States
facility: Froedtert Memorial Lutheran Hospital /ID# 119081
state: Wisconsin
city: Linz
country: Austria
facility: KH der Elisabethinen Linz GmbH /ID# 126280
state: Oberoesterreich
city: Vienna
country: Austria
facility: Medizinische Universitat Wien /ID# 126279
state: Wien
city: Innsbruck
country: Austria
facility: Medizinische Universitat Innsbruck,Universitatsklinik fur Innere Medizin 1 /ID# 126249
city: Salzburg
country: Austria
facility: LKH Salzburg and Paracelsus /ID# 126248
city: St Veit An Der Glan
country: Austria
facility: Krankenhaus der Barmherzigen Bruder /ID# 126270
city: Ghent
country: Belgium
facility: AZ Maria Middelares /ID# 126194
city: Ghent
country: Belgium
facility: AZ Sint-Lucas /ID# 126242
city: Leuven
country: Belgium
facility: UZ Leuven /ID# 126240
city: Liege
country: Belgium
facility: CHU de Liege /ID# 126241
city: Roeselare
country: Belgium
facility: AZ-Delta /ID# 126195
city: Calgary
country: Canada
facility: University of Calgary Cumming School of Medicine Adult Cystic Fibrosis Clinic /ID# 119017
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta /ID# 119022
state: Alberta
city: Winnipeg
country: Canada
facility: Winnipeg Regional Health Authority /ID# 119015
state: Manitoba
city: Halifax
country: Canada
facility: Qe Ii Hsc /Id# 127115
state: Nova Scotia
city: London
country: Canada
facility: London Health Sciences Centre - University Hospital /ID# 119026
state: Ontario
city: Sudbury
country: Canada
facility: Medicor Research Inc /ID# 119024
state: Ontario
city: Vaughan
country: Canada
facility: Toronto Digestive Disease Asso /ID# 119019
state: Ontario
city: Montreal
country: Canada
facility: Montreal General Hospital - McGill University Health Center /ID# 119025
state: Quebec
city: Olomouc
country: Czechia
facility: Fakultni Nemocnice Olomouc /ID# 126264
state: Olomoucky Kraj
city: Ceske Budejovice
country: Czechia
facility: Nemocnice Ceske Budejovice a.s. /ID# 126266
city: Hradec Kralove
country: Czechia
facility: Hepato-Gastroenterologie HK s.r.o. /ID# 126269
city: Praha 9
country: Czechia
facility: ISCARE a.s. /ID# 137977
city: Usti Nad Labem
country: Czechia
facility: Krajska zdravotni a.s. Masarykova nemocnice v Usti nad Labem o.z. /ID# 138331
city: Herlev
country: Denmark
facility: Herlev Hospital /ID# 127741
state: Hovedstaden
city: Silkeborg
country: Denmark
facility: Silkeborg Hospital /ID# 126251
city: Lille CEDEX
country: France
facility: CHRU Lille - Hopital Claude Huriez /ID# 127743
state: Hauts-de-France
city: Vandoeuvre les Nancy CEDEX
country: France
facility: CHU NANCY - Hopital Brabois Adultes /ID# 127742
state: Meurthe-et-Moselle
city: Amiens CEDEX 1
country: France
facility: CHU Amiens-Picardie Site Sud /ID# 126237
state: Somme
city: Grenoble
country: France
facility: Centre Hospitalier Universitaire de Grenoble - Hopital Michallon /ID# 126200
city: Nice
country: France
facility: Hopital l'Archet 2 /ID# 126238
city: SAINT-ETIENNE Cedex 1
country: France
facility: CHU de Saint-Etienne, Hopital Nord /ID# 134450
city: Toulouse
country: France
facility: Hopital Rangueil /ID# 126239
city: Kiel
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein /ID# 126260
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: Charite Universitaetsmedizin Berlin /ID# 126196
city: Berlin
country: Germany
facility: Private Practice - Dr. Michael R. MroB Dipl. med. S. Schache /ID# 126257
city: Hamburg
country: Germany
facility: Israelitisches Krankenhaus Hamburg /ID# 136549
city: Hamburg
country: Germany
facility: Asklepios Westklinikum Hamburg /ID# 126275
city: Jena
country: Germany
facility: Universitaetsklinikum Jena /ID# 126261
city: Leipzig
country: Germany
facility: EUGASTRO GmbH /ID# 126259
city: Magdeburg
country: Germany
facility: Universitatsklinikum Magdeburg /ID# 126256
city: Munster
country: Germany
facility: Gastro Campus Research GbR /ID# 126274
city: Budapest
country: Hungary
facility: Semmelweis Egyetem /ID# 137896
city: Budapest
country: Hungary
facility: Magyar Elhizastudomanyi KKft. /ID# 126276
city: Pecs
country: Hungary
facility: Pecsi Tudomanyegyetem Klinikai l.sz. Belgyogyaszati Klinika /ID# 137895
city: Szeged
country: Hungary
facility: University of Szeged /ID# 126263
city: Petakh Tikva
country: Israel
facility: Rabin Medical Center /ID# 126198
state: Tel-Aviv
city: Be'er Sheva
country: Israel
facility: Soroka University Medical Center /ID# 126243
city: Jerusalem
country: Israel
facility: Gastroenterology Institute, Division of Medicine /ID# 126245
city: Rehovot
country: Israel
facility: Kaplan Medical Center /ID# 126246
city: Rome
country: Italy
facility: UOSD - Azienda Ospedaliera San Camillo Forlanini /ID# 127745
state: Lazio
city: Rome
country: Italy
facility: Policlinico Agostino Gemelli /ID# 127746
state: Lazio
city: Milan
country: Italy
facility: Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico /ID# 126221
state: Lombardia
city: Rozzano
country: Italy
facility: IBD Center - IRCCS Istituto Clinico Humanitas /ID# 126226
state: Milano
city: Brescia
country: Italy
facility: Azienda Ospedaliera Spedali Civili /ID# 127744
city: Padua
country: Italy
facility: Azienda Ospedaliera di Padova /ID# 126267
city: San Giovanni Rotondo
country: Italy
facility: Fondazione di Religione e di Culto Casa Sollievo della Sofferenza /ID# 129856
city: Amsterdam
country: Netherlands
facility: Academisch Medical center Amsterdam /ID# 126227
state: Noord-Holland
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum /ID# 126228
city: Rotterdam
country: Netherlands
facility: Sint Franciscus Gasthuis /ID# 127877
city: Lodz
country: Poland
facility: Centrum.Medyczne. Szpital Swietej Rodziny /ID# 137974
state: Lodzkie
city: Warszawa
country: Poland
facility: Endoterapia PFG sp. z o.o. /ID# 126199
state: Mazowieckie
city: Bydgoszcz
country: Poland
facility: Centrum Endoskopii Zabiegowej /ID# 126272
city: Czestochowa
country: Poland
facility: Centrum Medyczne sw. Lukasza Sp. z o.o. /ID# 126271
city: Pulawy
country: Poland
facility: KO-Med Centra Kliniczne Pulawi /ID# 126278
city: Warsaw
country: Poland
facility: NZOZ Vivamed /ID# 126255
city: San Juan
country: Puerto Rico
facility: School of Medicine University of Puerto Rico-Medical Science Campus /ID# 137735
city: Sector 2
country: Romania
facility: Institutul Clinic Fundeni /ID# 127747
state: Bucuresti
city: Brasov
country: Romania
facility: Centrul Medical de Diagnostic si Tratament Ambulator Neomed SRL /ID# 126277
city: Cluj
country: Romania
facility: Tvm Med Serv Srl /Id# 126268
city: Oradea
country: Romania
facility: Cabinet Medical Dr. Fratila SRL /ID# 126247
city: Zalau
country: Romania
facility: Salvo-san Ciobanca SRL / Medicina Interna /ID# 126224
city: Bratislava
country: Slovakia
facility: Gastroenterologicke centrum ASSIDUO a IBD centrum /ID# 126262
city: Bratislava
country: Slovakia
facility: Gastroenterologicka ambulancia /ID# 137964
city: Lucenec
country: Slovakia
facility: Vseobecna Nemocnica s poliklinikou Lucenec n.o. /ID# 127748
city: Nove Mesto Nad Vahom
country: Slovakia
facility: Poliklinika Libris /ID# 126222
city: Sabadell
country: Spain
facility: Hospital Parc Tauli de Sabadell /ID# 138124
state: Barcelona
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro, Majadahonda /ID# 140425
state: Madrid
city: Barcelona
country: Spain
facility: Hospital Clinic /ID# 127749
city: Girona
country: Spain
facility: Hospital Universitario de Girona Doctor Josep Trueta /ID# 137976
city: Leon
country: Spain
facility: Hospital de Leon /ID# 141675
city: Madrid
country: Spain
facility: Hospital Clinico Universitario San Carlos /ID# 126253
city: Pontevedra
country: Spain
facility: Complejo Hospitalario Universitario de Pontevedra /ID# 138126
city: Zaragoza
country: Spain
facility: Hospital Clinico Universitario Lozano Blesa /ID# 126252
city: St. Gallen
country: Switzerland
facility: Kantonsspital St. Gallen /ID# 127750
state: Sankt Gallen
city: Zurich
country: Switzerland
facility: Universitaetsspital Zuerich /ID# 127751
state: Zuerich
city: Kharkiv
country: Ukraine
facility: State Institution L. T. Malaya Therapy National Institution of NAMS of Ukraine /ID# 127753
state: Kharkivska Oblast
city: Kherson
country: Ukraine
facility: Public Institution Kherson City Clinical Hospital named after le.le. Karabelesha /ID# 127754
city: Kiev
country: Ukraine
facility: Kyiv City Clinical Hospital No.8 /ID# 126232
city: Lviv
country: Ukraine
facility: Lviv Regional Clinical Hospital /ID# 126234
city: Zaporizhzhia
country: Ukraine
facility: Public Institution 6th City Clinical Hospital /ID# 126236
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS Found /ID# 144366
state: London, City Of
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich Univ Hosp /ID# 126197
state: Norfolk
city: Hull
country: United Kingdom
facility: Hull University Teaching Hospitals NHS Trustust /ID# 126265
city: Southampton
country: United Kingdom
facility: University Hospital Southampton NHS Fundation Trust /ID# 126225
city: Wolverhampton
country: United Kingdom
facility: The Royal Wolverhampton NHS Tr /ID# 126201
Study officials:
affiliation: AbbVie
name: AbbVie Inc.
role: STUDY_DIRECTOR
References:
citation: D'Haens GR, Sandborn WJ, Loftus EV Jr, Hanauer SB, Schreiber S, Peyrin-Biroulet L, Panaccione R, Panes J, Baert F, Colombel JF, Ferrante M, Louis E, Armuzzi A, Zhou Q, Goteti VS, Mostafa NM, Doan TT, Petersson J, Finney-Hayward T, Song AP, Robinson AM, Danese S. Higher vs Standard Adalimumab Induction Dosing Regimens and Two Maintenance Strategies: Randomized SERENE CD Trial Results. Gastroenterology. 2022 Jun;162(7):1876-1890. doi: 10.1053/j.gastro.2022.01.044. Epub 2022 Feb 3.
citation: Greener T, Boland K, Milgrom R, Ben-Bassat O, Steinhart AH, Silverberg MS, Narula N. Higher adalimumab maintenance regimen is more effective than standard dose in anti-TNF experienced Crohn's disease patients. Eur J Gastroenterol Hepatol. 2021 Oct 1;33(10):1274-1279. doi: 10.1097/MEG.0000000000002250.