A Study to Evaluate Efficacy and Safety of Ustekinumab Re-induction Therapy in Participants With Moderately to Severely Active Crohn's Disease

NCT ID: NCT03782376

Last Updated: 2025-04-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 215 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-20
• Study Completion Date: 2023-01-10

Brief Summary

The primary purpose of this study is to evaluate the efficacy and safety of a single intravenous (IV) re-induction dose of approximately 6 milligram per kilogram (mg/kg) ustekinumab in participants with secondary loss of response (LoR) to subcutaneous (SC) every 8 Weeks (q8w) 90 mg ustekinumab maintenance therapy.

Detailed Description

This study compares the efficacy and safety of a single weight-tiered based IV re-induction dose of approximately 6 mg/kg ustekinumab versus continuing with regular SC q8w 90 mg ustekinumab administration. It consists of screening (5 weeks); treatment period (Week 0 to 24); and safety follow up visit (20 weeks after last dose). The primary hypothesis is that a single IV re-induction dose of ustekinumab is superior to continuing with regular SC q8w maintenance treatment as measured by clinical response after 16 weeks of treatment. Study assessments will include Crohn's disease activity index (CDAI), video ileocolonoscopy, 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 be randomly assigned to receive either ustekinumab IV re-induction or regular SC q8w 90 mg ustekinumab injection at baseline in a double dummy design. 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 (IV re-induction)

Participants who experience a secondary loss of response (LoR) to 90 mg ustekinumab maintenance treatment, administered subcutaneously every 8 weeks (q8w) will receive a weight-tiered based ustekinumab IV re-induction dose of approximately 6 mg/kg and matching placebo subcutaneously at Week 0. At Weeks 8 and 16, all participants will receive SC maintenance injections of 90 mg ustekinumab. Participants will resume their standard-of-care therapy at Week 24 at the discretion of the treating physician.

Group Type: EXPERIMENTAL

Ustekinumab approximately 6 mg/kg (IV)

Intervention Type: DRUG

Participants will receive ustekinumab approximately 6mg/kg intravenously at Week 0.

Placebo (SC)

Intervention Type: DRUG

Participants will receive SC injection of placebo at Week 0.

Ustekinumab 90 mg (SC) Group 1

Intervention Type: DRUG

Participants will receive SC injection of ustekinumab 90 mg at Weeks 8 and 16.

Group 2: Ustekinumab (Continuous q8w SC maintenance)

Participants who experience a secondary LoR to 90 mg ustekinumab maintenance treatment, administered subcutaneously q8w will receive ustekinumab 90 mg subcutaneously and matching placebo intravenously at Week 0. At Weeks 8 and 16, all participants will receive SC maintenance injections of 90 mg ustekinumab. Participants will resume their standard-of-care therapy at Week 24 at the discretion of the treating physician.

Group Type: ACTIVE_COMPARATOR

Placebo (IV)

Intervention Type: DRUG

Participants will receive IV infusion of placebo at Week 0.

Ustekinumab 90 mg (SC) Group 2

Intervention Type: DRUG

Participants will receive SC injection of ustekinumab 90 mg at Weeks 0, 8 and 16.

Interventions

Ustekinumab approximately 6 mg/kg (IV)

Participants will receive ustekinumab approximately 6mg/kg intravenously at Week 0.

Intervention Type: DRUG

Placebo (SC)

Participants will receive SC injection of placebo at Week 0.

Intervention Type: DRUG

Placebo (IV)

Participants will receive IV infusion of placebo at Week 0.

Intervention Type: DRUG

Ustekinumab 90 mg (SC) Group 1

Participants will receive SC injection of ustekinumab 90 mg at Weeks 8 and 16.

Intervention Type: DRUG

Ustekinumab 90 mg (SC) Group 2

Participants will receive SC injection of ustekinumab 90 mg at Weeks 0, 8 and 16.

Intervention Type: DRUG

Other Intervention Names

STELARA; STELARA; STELARA

Eligibility Criteria

Inclusion Criteria

• A history of Crohn's disease or fistulizing Crohn's disease of at least 3 months' duration, with colitis, ileitis, or ileocolitis, confirmed at any time in the past by radiography, histology, and/or endoscopy
• Currently receiving subcutaneous 90 mg every 8 weeks (q8w) ustekinumab maintenance therapy and initially responded to ustekinumab induction therapy, administered according to the local label, followed by secondary loss of response (LoR) to ustekinumab. Secondary LoR to ustekinumab is defined as active disease at study baseline, proven by a Crohn's Disease Activity Index (CDAI) score of greater than or equal to (>=) 220 and <=450 with at least one of the following: Elevated C-reactive protein (CRP) (>3.0 milligram per liter [mg/L]); and/or elevated Fecal calprotectin (fCal) >250 milligram per kilogram [mg/kg]); and/or endoscopy (performed less than or equal to (<=) 3 months before baseline) with evidence of active Crohn's disease, (defined as one or more ulcerations in the ileum and/or colon)
• Participants receiving either oral 5-aminosalicylic acid (5-ASA) compounds, oral corticosteroids (for example {e.g.}, prednisone, budesonide) at a prednisone-equivalent dose of <=40 mg/day or <=9 mg/day of budesonide, antibiotics used as the primary treatment of Crohn's disease, or conventional immunomodulators (i.e., azathioprine [AZA], 6-mercaptopurine [6-MP], or methotrexate [MTX]) are permitted providing the doses indicated are stable before baseline or have been discontinued before baseline within the protocol defined durations

Exclusion Criteria

• Complications of Crohn's disease, such as symptomatic strictures or stenoses, short gut syndrome, or any other manifestation that might be anticipated to require surgery, could preclude the use of the CDAI to assess response to therapy, or would possibly confound the ability to assess the effect of treatment with ustekinumab
• 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 before baseline (or 8 weeks before baseline for intra-abdominal abscesses) provided 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 identified
• Any kind of bowel resection within 6 months or any other intra-abdominal surgery within 3 months before baseline
• A draining (i.e., functioning) stoma or ostomy
• Received ustekinumab intravenous re-induction after the initial weight-tiered-based IV induction dose of ustekinumab
• Any known history of shortened frequency of SC dose administration (<q8w) for a secondary loss of response where the participant did not, in the opinion of the treating physician, benefit from the dose interval shortening

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

Sponsors

Janssen-Cilag Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen-Cilag Ltd. Clinical Trial

Role: STUDY_DIRECTOR

Janssen-Cilag Ltd.

Locations

University of California, San Diego

La Jolla, California, United States

Peak Gastroenterology Associates

Colorado Springs, Colorado, United States

Florida Research Network, LLC

Gainesville, Florida, United States

Mayo Clinic Jacksonville

Jacksonville, Florida, United States

Advent Health

Orlando, Florida, United States

Florida Hospital Tampa

Tampa, Florida, United States

Emory University

Atlanta, Georgia, United States

Atlanta Gastroenterology Associates, (AGA) LLC - Emory Saint Joseph's

Atlanta, Georgia, United States

Atlanta Gastroenterology Specialists

Suwanee, Georgia, United States

University of Kentucky Chandler Medical Center

Lexington, Kentucky, United States

Chevy Chase Clinical Research

Chevy Chase, Maryland, United States

Brigham And Women's Hospital

Boston, Massachusetts, United States

University of Mississippi Medical Center

Jackson, Mississippi, United States

Washington University School Of Medicine

St Louis, Missouri, United States

Mount Sinai School of Medicine

New York, New York, United States

Ohio State University Hospital

Hilliard, Ohio, United States

Northshore Gastroenterology Research, LLC

Westlake, Ohio, United States

Oklahoma Digestive Disease Specialists

Oklahoma City, Oklahoma, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Texas Digestive Disease Consultants

Cedar Park, Texas, United States

Baylor College of Medicine

Houston, Texas, United States

Houston Methodist Hospital

Houston, Texas, United States

Gastroenterology Research of America, LLC

San Antonio, Texas, United States

Tyler Research Institute, LLC

Tyler, Texas, United States

Virginia Mason Medical Center

Seattle, Washington, United States

University of Washington

Seattle, Washington, United States

Washington Gastroenterology, PLLC

Tacoma, Washington, United States

Krankenhaus der Barmherzigen Brüder

Vienna, , Austria

Medizinische Universitaet Wien

Vienna, , Austria

Hepato-gastroenterologie HK, s.r.o.

Hradec Králové, , Czechia

ISCARE a.s.

Prague, , Czechia

Hopital Beaujon

Clichy, , France

CHRU de Lille Hopital Claude Huriez

Lille, , France

CHRU Montpellier - Hopital Saint-Eloi

Montpellier, , France

CHU Hopital Saint Antoine

Paris, , France

Hospices Civils de Lyon HCL

Pierre-Bénite, , France

CHRU Hopital de Pontchaillou

Rennes, , France

CHU de Nancy_ Hopital Brabois

Vandœuvre-lès-Nancy, , France

Klinikum Augsburg

Augsburg, , Germany

GASTRO-Studien

Berlin, , Germany

Charite - Universitaetsmedizin Berlin (CCM)

Berlin, , Germany

Medizinisches Versorgungszentrum (MVZ) Dachau

Dachau, , Germany

University Hospital Dresden

Dresden, , Germany

Agaplesion Frankfurter Diakonie Kliniken GmbH, Markus Krankenhaus

Frankfurt, , Germany

Universitatsklinikum Frankfurt/ Medizinische Klinik 1

Frankfurt, , Germany

Universitatsklinikum Freiburg

Freiburg im Breisgau, , Germany

Städtisches Krankenhaus Martha-Maria Halle-Dölau gGmbH

Halle, , Germany

Hamburgisches Forschungsinstitut fuer CED, HaFCED e.K.

Hamburg, , Germany

Gastroenterologie Opernstrasse

Kassel, , Germany

Universitatsklinikum Schleswig Holstein Kiel

Kiel, , Germany

Staedtisches Klinikum Lueneburg

Lüneburg, , Germany

Universitätsklinikum Otto-von-Guericke-Universität Magdeburg

Magdeburg, , Germany

Medizinische Fakultät Mannheim der Universität Heidelberg

Mannheim, , Germany

Gastroenterologische Gemeinschaftspraxis Minden

Minden, , Germany

Klinikum der Universitaet Muenchen

München, , Germany

Praxis Dr. med. Ulf Helwig

Oldenburg, , Germany

Zentrum für Gastroenterologie Saar MVZ GmbH

Saarbrücken, , Germany

Universitaetsklinik Tuebingen

Tübingen, , Germany

Universitaetsklinikum Ulm, Klinik fuer Innere Medizin II

Ulm, , Germany

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico

Milan, , Italy

Ospedale Villa Sofia-Cervello

Palermo, , Italy

Azienda Ospedaliera G.Salvini Ospedale di Rho

Rho, , Italy

Fondazione Policlinico Gemelli Università Cattolica

Roma, , Italy

Istituto Clinico Humanitas

Rozzano, , Italy

AO Ordine Mauriziano

Torino, , Italy

Onze Lieve Vrouwe Gasthuis

Amsterdam, , Netherlands

Leiden University Medical Center

Leiden, , Netherlands

Maastricht Universitair Medisch Centrum

Maastricht, , Netherlands

Radboudumc

Nijmegen, , Netherlands

Erasmus MC

Rotterdam, , Netherlands

Sint Franciscus Gasthuis

Rotterdam, , Netherlands

Irkutsk State Medical Academy of Postgraduate Education

Irkutsk, , Russia

Olla-Med, Llc

Moscow, , Russia

City Clinical Hospital #31

Saint Petersburg, , Russia

GBUZ Respublican Clinical Hospital n.a. GG Kuvatova

Ufa, , Russia

Inje University Haeundae Paik Hospital

Busan, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Severance Hospital Yonsei University Health System

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

KyungHee University Hospital

Seoul, , South Korea

Hosp. Univ. Fundacion Alcorcon

Alcorcón, , Spain

Hosp. Arquitecto Marcide

Ferrol, , Spain

Hosp. Gral. Univ. Gregorio Maranon

Madrid, , Spain

Hosp. Univ. La Paz

Madrid, , Spain

Hosp Virgen de La Victoria

Málaga, , Spain

Hosp. Univ. Virgen de La Arrixaca

Murcia, , Spain

Hosp. de Navarra

Pamplona, , Spain

Hosp. Montecelo

Pontevedra, , Spain

Corporacio Sanitari Parc Tauli

Sabadell, , Spain

Hosp Clinico Univ de Salamanca

Salamanca, , Spain

Hosp. Univ. Marques de Valdecilla

Santander, , Spain

Hosp. Clinico Univ. de Valencia

Valencia, , Spain

Hosp. Alvaro Cunqueiro

Vigo, , Spain

Hosp. Clinico Univ. Lozano Blesa

Zaragoza, , Spain

Hosp. Univ. Miguel Servet

Zaragoza, , Spain

Gastromottagningen

Malmo, , Sweden

Gastromottagningen

Stockholm, , Sweden

Pennine Acute Hospitals-Fairfield General Hospital

Bury, , United Kingdom

Gloucestershire Hospitals NHS Foundation Trust - Cheltenham

Cheltenham, , United Kingdom

Royal Devon & Exeter Hospital

Exeter, , United Kingdom

King's College Hospital NHS Foundation Trust

London, , United Kingdom

St George's Hospital

London, , United Kingdom

Southampton University Hospitals NHS Trust

Southampton, , United Kingdom

Countries

United States; Austria; Czechia; France; Germany; Italy; Netherlands; Russia; South Korea; Spain; Sweden; 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)

Ten Bokkel Huinink S, Biemans V, Duijvestein M, Pierik M, Hoentjen F, West RL, van der Woude CJ, de Vries AC. Re-induction with intravenous Ustekinumab after secondary loss of response is a valid optimization strategy in Crohn's disease. Eur J Gastroenterol Hepatol. 2021 Dec 1;33(1S Suppl 1):e783-e788. doi: 10.1097/MEG.0000000000002256.

Reference Type: DERIVED

PMID: 34334713 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2018-002629-51

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CNTO1275CRD3008

Identifier Type: OTHER

Identifier Source: secondary_id

CR108533

Identifier Type: -

Identifier Source: org_study_id