Study to Evaluate Efficacy and Safety of Two Drug Regimens in Subjects With Moderate to Severe Crohn's Disease

NCT ID: NCT02065570

Last Updated: 2021-02-18

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

514 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-05-01

Study Completion Date

2020-01-30

Brief Summary

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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.

Detailed Description

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Conditions

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Crohn's Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Induction: Standard Induction Dose

Participants randomized to receive received blinded adalimumab 160 mg at Baseline and matching placebo at Week 1, adalimumab 80 mg and matching placebo at Week 2, matching placebo at Week 3, and then adalimumab 40 mg every other week (eow) starting at Week 4 through Week 12.

Group Type EXPERIMENTAL

Adalimumab

Intervention Type DRUG

Placebo

Intervention Type DRUG

Induction: Higher Induction Dose

Participants randomized to receive blinded adalimumab 160 mg at Baseline, Week 1, Week 2, and Week 3. At Week 4, participants receive adalimumab 40 mg eow through Week 12.

Group Type EXPERIMENTAL

Adalimumab

Intervention Type DRUG

Maintenance: Clinically Adjusted (CA) Regimen

Participants randomized to the CA regimen receive adalimumab 40 mg eow beginning at Week 12. The adalimumab dose will be escalated to every week (ew) starting as early as Week 14 and up to Week 54 based on Crohn's Disease Activity Index (CDAI) or high-sensitivity C-reactive protein (hs-CRP) values, using results from the prior or current study visit. Once participants in the CA regimen are escalated, they remain on adalimumab 40 mg ew dosing.

Group Type EXPERIMENTAL

Adalimumab

Intervention Type DRUG

Maintenance: Therapeutic Drug Monitoring (TDM) Regimen

At Weeks 14, 28 and 42, the adalimumab dose for participants randomized to the TDM will be determined by protocol-established dose adjustment criteria. Doses will be determined using blinded serum concentrations at the prior visit (Weeks 12, 26 and 40, respectively) as well as the CDAI or hs-CRP values from the current or prior study visit. Participants who meet criteria for dose escalation at Weeks 14, 28 or 42 will receive 40 mg ew.

Group Type EXPERIMENTAL

Adalimumab

Intervention Type DRUG

Interventions

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Adalimumab

Intervention Type DRUG

Placebo

Intervention Type DRUG

Other Intervention Names

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Humira

Eligibility Criteria

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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).
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AbbVie

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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AbbVie Inc.

Role: STUDY_DIRECTOR

AbbVie

Locations

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Birmingham Gastroenterology Associates O.C /ID# 137282

Birmingham, Alabama, United States

Site Status

Digestive Health Specialists of the Southeast /ID# 122483

Dothan, Alabama, United States

Site Status

Moore UC San Diego Cancer Center /ID# 119053

La Jolla, California, United States

Site Status

Axis Clinical Trials /ID# 130390

Los Angeles, California, United States

Site Status

Rocky Mountain Gastroenterology /ID# 119038

Wheat Ridge, Colorado, United States

Site Status

Medical Research Ctr CT /ID# 119037

Hamden, Connecticut, United States

Site Status

Gastroenterology Group Naples /ID# 122493

Naples, Florida, United States

Site Status

Internal Med Specialists /ID# 137737

Orlando, Florida, United States

Site Status

Shafran Gastroenterology Ctr /ID# 119057

Winter Park, Florida, United States

Site Status

Winship Cancer Institute of Emory University /ID# 136851

Atlanta, Georgia, United States

Site Status

Atlanta Gastro Assoc /ID# 119065

Atlanta, Georgia, United States

Site Status

Gastroenterology Associates of Central Georgia, LLC /ID# 119056

Macon, Georgia, United States

Site Status

Northwestern University Feinberg School of Medicine /ID# 119043

Chicago, Illinois, United States

Site Status

University of Chicago DCAM /ID# 119077

Chicago, Illinois, United States

Site Status

Carle Foundation Hospital Digestive Health Research Center /ID# 136008

Urbana, Illinois, United States

Site Status

Louisana Research Center, LLC /ID# 136749

Shreveport, Louisiana, United States

Site Status

Investigative Clinical Research /ID# 119033

Annapolis, Maryland, United States

Site Status

MGG Group Co, Inc.Chevy Chase Clinical Research /ID# 119042

Chevy Chase, Maryland, United States

Site Status

Commonwealth Clinical Studies /ID# 136850

Brockton, Massachusetts, United States

Site Status

University of Michigan Health Systems /ID# 119076

Ann Arbor, Michigan, United States

Site Status

Minnesota Gastroenterology, P. A. /ID# 137280

Plymouth, Minnesota, United States

Site Status

Mayo Clinic /ID# 122489

Rochester, Minnesota, United States

Site Status

Kansas City Research Institute /ID# 119034

Kansas City, Missouri, United States

Site Status

Ctr for Digest and Liver Dis /ID# 119040

Mexico, Missouri, United States

Site Status

Albany Medical College /ID# 140200

Albany, New York, United States

Site Status

NYU Langone Long Island Clinical Research Associates /ID# 119035

Great Neck, New York, United States

Site Status

The Mount Sinai Hospital /ID# 127116

New York, New York, United States

Site Status

Charlotte Gastroenterology and Hepatology, PLLC /ID# 119041

Charlotte, North Carolina, United States

Site Status

Wake Research Associates, LLC /ID# 119029

Raleigh, North Carolina, United States

Site Status

Consultants for Clinical Res /ID# 119052

Cincinnati, Ohio, United States

Site Status

Gastro United of Tulsa /ID# 122485

Tulsa, Oklahoma, United States

Site Status

The Oregon Clinic, Gastroenterology - West /ID# 135272

Portland, Oregon, United States

Site Status

West Bay Clinical Research /ID# 138330

Warwick, Rhode Island, United States

Site Status

Medical University of South Carolina /ID# 138122

Charleston, South Carolina, United States

Site Status

Erlanger Institute for Clinical Research /ID# 129008

Chattanooga, Tennessee, United States

Site Status

Gastro One /ID# 119068

Germantown, Tennessee, United States

Site Status

Nashville Med Res Inst /ID# 119050

Nashville, Tennessee, United States

Site Status

Vanderbilt Univ Med Ctr /ID# 125501

Nashville, Tennessee, United States

Site Status

Texas Digestive Disease Consultants - Dallas /ID# 138121

Dallas, Texas, United States

Site Status

Baylor College of Medicine /ID# 137277

Houston, Texas, United States

Site Status

Austin Institute for Clinical Research /ID# 125500

Pflugerville, Texas, United States

Site Status

Texas Digestive Disease Consultants - Southlake /ID# 137283

Southlake, Texas, United States

Site Status

Advanced Research Institute /ID# 119048

Ogden, Utah, United States

Site Status

University of Utah /ID# 119062

Salt Lake City, Utah, United States

Site Status

Gastro Assoc of Tidewater /ID# 135897

Chesapeake, Virginia, United States

Site Status

New River Valley Research Inst /ID# 127807

Christiansburg, Virginia, United States

Site Status

Wisconsin Center for Advanced Research, a division of GI Associates, LLC /ID# 119036

Milwaukee, Wisconsin, United States

Site Status

Froedtert Memorial Lutheran Hospital /ID# 119081

Milwaukee, Wisconsin, United States

Site Status

KH der Elisabethinen Linz GmbH /ID# 126280

Linz, Upper Austria, Austria

Site Status

Medizinische Universitat Wien /ID# 126279

Vienna, Vienna, Austria

Site Status

Medizinische Universitat Innsbruck,Universitatsklinik fur Innere Medizin 1 /ID# 126249

Innsbruck, , Austria

Site Status

LKH Salzburg and Paracelsus /ID# 126248

Salzburg, , Austria

Site Status

Krankenhaus der Barmherzigen Bruder /ID# 126270

Sankt Veit an der Glan, , Austria

Site Status

AZ Maria Middelares /ID# 126194

Ghent, , Belgium

Site Status

AZ Sint-Lucas /ID# 126242

Ghent, , Belgium

Site Status

UZ Leuven /ID# 126240

Leuven, , Belgium

Site Status

CHU de Liege /ID# 126241

Liège, , Belgium

Site Status

AZ-Delta /ID# 126195

Roeselare, , Belgium

Site Status

University of Calgary Cumming School of Medicine Adult Cystic Fibrosis Clinic /ID# 119017

Calgary, Alberta, Canada

Site Status

University of Alberta /ID# 119022

Edmonton, Alberta, Canada

Site Status

Winnipeg Regional Health Authority /ID# 119015

Winnipeg, Manitoba, Canada

Site Status

Qe Ii Hsc /Id# 127115

Halifax, Nova Scotia, Canada

Site Status

Medicor Research Inc /ID# 119024

Greater Sudbury, Ontario, Canada

Site Status

London Health Sciences Centre - University Hospital /ID# 119026

London, Ontario, Canada

Site Status

Toronto Digestive Disease Asso /ID# 119019

Vaughan, Ontario, Canada

Site Status

Montreal General Hospital - McGill University Health Center /ID# 119025

Montreal, Quebec, Canada

Site Status

Fakultni Nemocnice Olomouc /ID# 126264

Olomouc, Olomoucký kraj, Czechia

Site Status

Nemocnice Ceske Budejovice a.s. /ID# 126266

České Budějovice, , Czechia

Site Status

Hepato-Gastroenterologie HK s.r.o. /ID# 126269

Hradec Králové, , Czechia

Site Status

ISCARE a.s. /ID# 137977

Prague, , Czechia

Site Status

Krajska zdravotni a.s. Masarykova nemocnice v Usti nad Labem o.z. /ID# 138331

Ústí nad Labem, , Czechia

Site Status

Herlev Hospital /ID# 127741

Herlev, Capital Region, Denmark

Site Status

Silkeborg Hospital /ID# 126251

Silkeborg, , Denmark

Site Status

CHRU Lille - Hopital Claude Huriez /ID# 127743

Lille, Hauts-de-France, France

Site Status

CHU NANCY - Hopital Brabois Adultes /ID# 127742

Vandœuvre-lès-Nancy, Meurthe-et-Moselle, France

Site Status

CHU Amiens-Picardie Site Sud /ID# 126237

Amiens, Somme, France

Site Status

Centre Hospitalier Universitaire de Grenoble - Hopital Michallon /ID# 126200

Grenoble, , France

Site Status

Hopital l'Archet 2 /ID# 126238

Nice, , France

Site Status

CHU de Saint-Etienne, Hopital Nord /ID# 134450

Saint-Etienne, , France

Site Status

Hopital Rangueil /ID# 126239

Toulouse, , France

Site Status

Universitaetsklinikum Schleswig-Holstein /ID# 126260

Kiel, Schleswig-Holstein, Germany

Site Status

Charite Universitaetsmedizin Berlin /ID# 126196

Berlin, , Germany

Site Status

Private Practice - Dr. Michael R. MroB Dipl. med. S. Schache /ID# 126257

Berlin, , Germany

Site Status

Israelitisches Krankenhaus Hamburg /ID# 136549

Hamburg, , Germany

Site Status

Asklepios Westklinikum Hamburg /ID# 126275

Hamburg, , Germany

Site Status

Universitaetsklinikum Jena /ID# 126261

Jena, , Germany

Site Status

EUGASTRO GmbH /ID# 126259

Leipzig, , Germany

Site Status

Universitatsklinikum Magdeburg /ID# 126256

Magdeburg, , Germany

Site Status

Gastro Campus Research GbR /ID# 126274

Münster, , Germany

Site Status

Semmelweis Egyetem /ID# 137896

Budapest, , Hungary

Site Status

Magyar Elhizastudomanyi KKft. /ID# 126276

Budapest, , Hungary

Site Status

Pecsi Tudomanyegyetem Klinikai l.sz. Belgyogyaszati Klinika /ID# 137895

Pécs, , Hungary

Site Status

University of Szeged /ID# 126263

Szeged, , Hungary

Site Status

Rabin Medical Center /ID# 126198

Petakh Tikva, Tel Aviv, Israel

Site Status

Soroka University Medical Center /ID# 126243

Beersheba, , Israel

Site Status

Gastroenterology Institute, Division of Medicine /ID# 126245

Jerusalem, , Israel

Site Status

Kaplan Medical Center /ID# 126246

Rehovot, , Israel

Site Status

UOSD - Azienda Ospedaliera San Camillo Forlanini /ID# 127745

Rome, Lazio, Italy

Site Status

Policlinico Agostino Gemelli /ID# 127746

Rome, Lazio, Italy

Site Status

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico /ID# 126221

Milan, Lombardy, Italy

Site Status

IBD Center - IRCCS Istituto Clinico Humanitas /ID# 126226

Rozzano, Milano, Italy

Site Status

Azienda Ospedaliera Spedali Civili /ID# 127744

Brescia, , Italy

Site Status

Azienda Ospedaliera di Padova /ID# 126267

Padua, , Italy

Site Status

Fondazione di Religione e di Culto Casa Sollievo della Sofferenza /ID# 129856

San Giovanni Rotondo, , Italy

Site Status

Academisch Medical center Amsterdam /ID# 126227

Amsterdam, North Holland, Netherlands

Site Status

Erasmus Medisch Centrum /ID# 126228

Rotterdam, , Netherlands

Site Status

Sint Franciscus Gasthuis /ID# 127877

Rotterdam, , Netherlands

Site Status

Endoterapia PFG sp. z o.o. /ID# 126199

Warsaw, Masovian Voivodeship, Poland

Site Status

Centrum Endoskopii Zabiegowej /ID# 126272

Bydgoszcz, , Poland

Site Status

Centrum Medyczne sw. Lukasza Sp. z o.o. /ID# 126271

Częstochowa, , Poland

Site Status

KO-Med Centra Kliniczne Pulawi /ID# 126278

Puławy, , Poland

Site Status

NZOZ Vivamed /ID# 126255

Warsaw, , Poland

Site Status

Centrum.Medyczne. Szpital Swietej Rodziny /ID# 137974

Lodz, Łódź Voivodeship, Poland

Site Status

School of Medicine University of Puerto Rico-Medical Science Campus /ID# 137735

San Juan, , Puerto Rico

Site Status

Institutul Clinic Fundeni /ID# 127747

Sector 2, București, Romania

Site Status

Centrul Medical de Diagnostic si Tratament Ambulator Neomed SRL /ID# 126277

Brasov, , Romania

Site Status

Tvm Med Serv Srl /Id# 126268

Cluj-Napoca, , Romania

Site Status

Cabinet Medical Dr. Fratila SRL /ID# 126247

Oradea, , Romania

Site Status

Salvo-san Ciobanca SRL / Medicina Interna /ID# 126224

Zalău, , Romania

Site Status

Gastroenterologicke centrum ASSIDUO a IBD centrum /ID# 126262

Bratislava, , Slovakia

Site Status

Gastroenterologicka ambulancia /ID# 137964

Bratislava, , Slovakia

Site Status

Vseobecna Nemocnica s poliklinikou Lucenec n.o. /ID# 127748

Lučenec, , Slovakia

Site Status

Poliklinika Libris /ID# 126222

Nové Mesto nad Váhom, , Slovakia

Site Status

Hospital Parc Tauli de Sabadell /ID# 138124

Sabadell, Barcelona, Spain

Site Status

Hospital Universitario Puerta de Hierro, Majadahonda /ID# 140425

Majadahonda, Madrid, Spain

Site Status

Hospital Clinic /ID# 127749

Barcelona, , Spain

Site Status

Hospital Universitario de Girona Doctor Josep Trueta /ID# 137976

Girona, , Spain

Site Status

Hospital de Leon /ID# 141675

León, , Spain

Site Status

Hospital Clinico Universitario San Carlos /ID# 126253

Madrid, , Spain

Site Status

Complejo Hospitalario Universitario de Pontevedra /ID# 138126

Pontevedra, , Spain

Site Status

Hospital Clinico Universitario Lozano Blesa /ID# 126252

Zaragoza, , Spain

Site Status

Kantonsspital St. Gallen /ID# 127750

Sankt Gallen, Canton of St. Gallen, Switzerland

Site Status

Universitaetsspital Zuerich /ID# 127751

Zurich, Canton of Zurich, Switzerland

Site Status

State Institution L. T. Malaya Therapy National Institution of NAMS of Ukraine /ID# 127753

Kharkiv, Kharkivs’ka Oblast’, Ukraine

Site Status

Public Institution Kherson City Clinical Hospital named after le.le. Karabelesha /ID# 127754

Kherson, , Ukraine

Site Status

Kyiv City Clinical Hospital No.8 /ID# 126232

Kiev, , Ukraine

Site Status

Lviv Regional Clinical Hospital /ID# 126234

Lviv, , Ukraine

Site Status

Public Institution 6th City Clinical Hospital /ID# 126236

Zaporizhzhia, , Ukraine

Site Status

Guy's and St Thomas' NHS Found /ID# 144366

London, London, City of, United Kingdom

Site Status

Norfolk and Norwich Univ Hosp /ID# 126197

Norwich, Norfolk, United Kingdom

Site Status

Hull University Teaching Hospitals NHS Trustust /ID# 126265

Hull, , United Kingdom

Site Status

University Hospital Southampton NHS Fundation Trust /ID# 126225

Southampton, , United Kingdom

Site Status

The Royal Wolverhampton NHS Tr /ID# 126201

Wolverhampton, , United Kingdom

Site Status

Countries

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United States Austria Belgium Canada Czechia Denmark France Germany Hungary Israel Italy Netherlands Poland Puerto Rico Romania Slovakia Spain Switzerland Ukraine United Kingdom

References

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Battat R, Kandi S, Lacerda AP, Levine P, Neimark E, Feagan BG, Rubin DT, Ji QC, Chen X, Polakow SB. Association of bile acid diarrhea with symptoms and disease activity in Crohn's disease: post-hoc clinical trial analysis of serum 7a-hydroxy-4cholestern-3-one, C4, in patients with active Crohn's disease. J Crohns Colitis. 2025 May 8;19(5):jjaf053. doi: 10.1093/ecco-jcc/jjaf053.

Reference Type DERIVED
PMID: 40202488 (View on PubMed)

Reppell M, Zheng X, Dreher I, Blaes J, Regan E, Haslberger T, Guay H, Pivorunas V, Smaoui N. HLA-DQA1*05 Associates With Anti-Tumor Necrosis Factor Immunogenicity and Low Adalimumab Trough Concentrations in Inflammatory Bowel Disease Patients From the SERENE Ulcerative Colitis and Crohn's Disease Studies. J Crohns Colitis. 2025 Jan 11;19(1):jjae129. doi: 10.1093/ecco-jcc/jjae129.

Reference Type DERIVED
PMID: 39162746 (View on PubMed)

Verstockt B, Pivorunas V, Al Mahi N, Smaoui N, Guay H, Kennedy NA, Goodhand JR, Lin S, Bai BYH, Hanauer SB, Ferrante M, Panes J, Vermeire S. Baseline TREM-1 Whole Blood Gene Expression Does Not Predict Response to Adalimumab Treatment in Patients with Ulcerative Colitis or Crohn's Disease in the SERENE Studies. J Crohns Colitis. 2024 Apr 23;18(4):493-505. doi: 10.1093/ecco-jcc/jjad170.

Reference Type DERIVED
PMID: 37801628 (View on PubMed)

Ponce-Bobadilla AV, Stodtmann S, Chen MJ, Winzenborg I, Mensing S, Blaes J, Haslberger T, Laplanche L, Dreher I, Mostafa NM. Assessing the Impact of Immunogenicity and Improving Prediction of Trough Concentrations: Population Pharmacokinetic Modeling of Adalimumab in Patients with Crohn's Disease and Ulcerative Colitis. Clin Pharmacokinet. 2023 Apr;62(4):623-634. doi: 10.1007/s40262-023-01221-x. Epub 2023 Mar 11.

Reference Type DERIVED
PMID: 36905528 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35122766 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34402466 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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2013-001746-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

M14-115

Identifier Type: -

Identifier Source: org_study_id

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