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

NCT03782376 | Completed Phase 3 Results FDA Drug

• 3 other identifiers: CR1085332018-002629-51CNTO1275CRD3008
• Study Type: interventional
• Target: 215
• Locations: 12 countries
• Sites: 104

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.

Conditions

Crohn Disease

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Clinical Response at Week 16

  Clinical response was defined as greater than or equal to (\>=) 100-point reduction from baseline in Crohn's disease activity index (CDAI) score or a CDAI score \< 150 points. CDAI is validated multi-item measure of severity of illness derived as weighted sum of 8 different Crohn's disease (CD)-related variables (extra-intestinal manifestations, abdominal mass, weight, hematocrit, total number of liquid stools, abdominal pain/cramping, use of antidiarrheal drug(s) and/or opiates, and general well-being). The last 4 variables were scored over 7 days by participant on diary card. In general, CDAI score ranges from 0 to approximately 600; higher score=higher disease activities. Participants who had prohibited CD-related surgery, prohibited concomitant medication changes or discontinued study agent due to lack of efficacy or adverse event indicated to be of worsening CD prior to designated analysis timepoint were considered not to be in clinical response, regardless of their CDAI score.

  Week 16

Secondary Outcomes (17)

• Percentage of Participants With Clinical Remission at Week 16

  Week 16

• Percentage of Participants With Clinical Response at Week 8

  Week 8

• Percentage of Participants With Clinical Remission at Week 8

  Week 8

• Percentage of Participants With Normalization of C-reactive Protein (CRP) and/or Normalization of Fecal Calprotectin (fCal) Concentration at Week 16

  Week 16

• Percentage of Participants With Clinical Remission at Week 24

  Week 24

Study Arms (2)

Group 1: Ustekinumab (IV re-induction)

EXPERIMENTAL

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.

Drug: Ustekinumab approximately 6 mg/kg (IV); Drug: Placebo (SC); Drug: Ustekinumab 90 mg (SC) Group 1

Group 2: Ustekinumab (Continuous q8w SC maintenance)

ACTIVE COMPARATOR

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.

Drug: Placebo (IV); Drug: Ustekinumab 90 mg (SC) Group 2

Interventions

Ustekinumab approximately 6 mg/kg (IV) DRUG

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

Also known as: STELARA

Group 1: Ustekinumab (IV re-induction)

Placebo (SC) DRUG

Participants will receive SC injection of placebo at Week 0.

Group 1: Ustekinumab (IV re-induction)

Placebo (IV) DRUG

Participants will receive IV infusion of placebo at Week 0.

Group 2: Ustekinumab (Continuous q8w SC maintenance)

Ustekinumab 90 mg (SC) Group 1 DRUG

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

Also known as: STELARA

Group 1: Ustekinumab (IV re-induction)

Ustekinumab 90 mg (SC) Group 2 DRUG

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

Also known as: STELARA

Group 2: Ustekinumab (Continuous q8w SC maintenance)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Janssen-Cilag Ltd.: lead

Study Sites (104)

University of California, San Diego

La Jolla, California, 92093, United States

Location

Peak Gastroenterology Associates

Colorado Springs, Colorado, 80907, United States

Location

Florida Research Network, LLC

Gainesville, Florida, 32605, United States

Location

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

Location

Advent Health

Orlando, Florida, 32803, United States

Location

Florida Hospital Tampa

Tampa, Florida, 33613, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

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

Atlanta, Georgia, 30342-5020, United States

Location

Atlanta Gastroenterology Specialists

Suwanee, Georgia, 30024, United States

Location

University of Kentucky Chandler Medical Center

Lexington, Kentucky, 40536, United States

Location

Chevy Chase Clinical Research

Chevy Chase, Maryland, 20815, United States

Location

Brigham And Women's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39202, United States

Location

Washington University School Of Medicine

St Louis, Missouri, 63110, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

Ohio State University Hospital

Hilliard, Ohio, 43026, United States

Location

Northshore Gastroenterology Research, LLC

Westlake, Ohio, 44145, United States

Location

Oklahoma Digestive Disease Specialists

Oklahoma City, Oklahoma, 73112, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37212, United States

Location

Texas Digestive Disease Consultants

Cedar Park, Texas, 78613, United States

Location

Baylor College of Medicine

Houston, Texas, 77025, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030-2740, United States

Location

Gastroenterology Research of America, LLC

San Antonio, Texas, 78229, United States

Location

Tyler Research Institute, LLC

Tyler, Texas, 75701, United States

Location

Virginia Mason Medical Center

Seattle, Washington, 98101, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

Washington Gastroenterology, PLLC

Tacoma, Washington, 98405, United States

Location

Krankenhaus der Barmherzigen Brüder

Vienna, 1020, Austria

Location

Medizinische Universitaet Wien

Vienna, 1090, Austria

Location

Hepato-gastroenterologie HK, s.r.o.

Hradec Králové, 500 12, Czechia

Location

ISCARE a.s.

Prague, 190 00, Czechia

Location

Hopital Beaujon

Clichy, 92110, France

Location

CHRU de Lille Hopital Claude Huriez

Lille, 59037, France

Location

CHRU Montpellier - Hopital Saint-Eloi

Montpellier, 34295, France

Location

CHU Hopital Saint Antoine

Paris, 75571, France

Location

Hospices Civils de Lyon HCL

Pierre-Bénite, 69495, France

Location

CHRU Hopital de Pontchaillou

Rennes, 35033, France

Location

CHU de Nancy_ Hopital Brabois

Vandœuvre-lès-Nancy, 54511, France

Location

Klinikum Augsburg

Augsburg, D-86158, Germany

Location

GASTRO-Studien

Berlin, 10825, Germany

Location

Charite - Universitaetsmedizin Berlin (CCM)

Berlin, 12203, Germany

Location

Medizinisches Versorgungszentrum (MVZ) Dachau

Dachau, 85221, Germany

Location

University Hospital Dresden

Dresden, 1307, Germany

Location

Agaplesion Frankfurter Diakonie Kliniken GmbH, Markus Krankenhaus

Frankfurt, 60431, Germany

Location

Universitatsklinikum Frankfurt/ Medizinische Klinik 1

Frankfurt, 60590, Germany

Location

Universitatsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Städtisches Krankenhaus Martha-Maria Halle-Dölau gGmbH

Halle, 06120, Germany

Location

Hamburgisches Forschungsinstitut fuer CED, HaFCED e.K.

Hamburg, 20251, Germany

Location

Gastroenterologie Opernstrasse

Kassel, 34117, Germany

Location

Universitatsklinikum Schleswig Holstein Kiel

Kiel, 24105, Germany

Location

Staedtisches Klinikum Lueneburg

Lüneburg, 21339, Germany

Location

Universitätsklinikum Otto-von-Guericke-Universität Magdeburg

Magdeburg, 39120, Germany

Location

Medizinische Fakultät Mannheim der Universität Heidelberg

Mannheim, 68167, Germany

Location

Gastroenterologische Gemeinschaftspraxis Minden

Minden, 32423, Germany

Location

Klinikum der Universitaet Muenchen

München, 81377, Germany

Location

Praxis Dr. med. Ulf Helwig

Oldenburg, 26123, Germany

Location

Zentrum für Gastroenterologie Saar MVZ GmbH

Saarbrücken, 66111, Germany

Location

Universitaetsklinik Tuebingen

Tübingen, 72076, Germany

Location

Universitaetsklinikum Ulm, Klinik fuer Innere Medizin II

Ulm, 89081, Germany

Location

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

Ospedale Villa Sofia-Cervello

Palermo, 90146, Italy

Location

Azienda Ospedaliera G.Salvini Ospedale di Rho

Rho, Italy

Location

Fondazione Policlinico Gemelli Università Cattolica

Roma, 168, Italy

Location

Istituto Clinico Humanitas

Rozzano, 20089, Italy

Location

AO Ordine Mauriziano

Torino, 10128, Italy

Location

Onze Lieve Vrouwe Gasthuis

Amsterdam, 1091 AC, Netherlands

Location

Leiden University Medical Center

Leiden, 2333 ZA, Netherlands

Location

Maastricht Universitair Medisch Centrum

Maastricht, 6229 HX, Netherlands

Location

Radboudumc

Nijmegen, 6525 GA, Netherlands

Location

Erasmus MC

Rotterdam, 3015 GD, Netherlands

Location

Sint Franciscus Gasthuis

Rotterdam, 3045 PM, Netherlands

Location

Irkutsk State Medical Academy of Postgraduate Education

Irkutsk, 664079, Russia

Location

Olla-Med, Llc

Moscow, 105554, Russia

Location

City Clinical Hospital #31

Saint Petersburg, 197110, Russia

Location

GBUZ Respublican Clinical Hospital n.a. GG Kuvatova

Ufa, 450005, Russia

Location

Inje University Haeundae Paik Hospital

Busan, 48108, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

KyungHee University Hospital

Seoul, 102-1703, South Korea

Location

Hosp. Univ. Fundacion Alcorcon

Alcorcón, 28922, Spain

Location

Hosp. Arquitecto Marcide

Ferrol, 15405, Spain

Location

Hosp. Gral. Univ. Gregorio Maranon

Madrid, 28007, Spain

Location

Hosp. Univ. La Paz

Madrid, 28046, Spain

Location

Hosp Virgen de La Victoria

Málaga, 29010, Spain

Location

Hosp. Univ. Virgen de La Arrixaca

Murcia, 30120, Spain

Location

Hosp. de Navarra

Pamplona, 31008, Spain

Location

Hosp. Montecelo

Pontevedra, 36071, Spain

Location

Corporacio Sanitari Parc Tauli

Sabadell, 08208, Spain

Location

Hosp Clinico Univ de Salamanca

Salamanca, 37007, Spain

Location

Hosp. Univ. Marques de Valdecilla

Santander, 39008, Spain

Location

Hosp. Clinico Univ. de Valencia

Valencia, 46010, Spain

Location

Hosp. Alvaro Cunqueiro

Vigo, 36213, Spain

Location

Hosp. Clinico Univ. Lozano Blesa

Zaragoza, 50009, Spain

Location

Hosp. Univ. Miguel Servet

Zaragoza, 50009, Spain

Location

Gastromottagningen

Malmo, 20502, Sweden

Location

Gastromottagningen

Stockholm, 18288, Sweden

Location

Pennine Acute Hospitals-Fairfield General Hospital

Bury, BL9 7TD, United Kingdom

Location

Gloucestershire Hospitals NHS Foundation Trust - Cheltenham

Cheltenham, GL53 7AN, United Kingdom

Location

Royal Devon & Exeter Hospital

Exeter, EX2 5DW, United Kingdom

Location

King's College Hospital NHS Foundation Trust

London, SE5 9RS, United Kingdom

Location

St George's Hospital

London, SW17 OQT, United Kingdom

Location

Southampton University Hospitals NHS Trust

Southampton, SO16 6YD, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 40357993 DERIVED

• 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.

  PMID: 34334713 DERIVED

MeSH Terms

Conditions

Crohn Disease

Interventions

Ustekinumab

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Some exploratory endpoints including endoscopic assessments for baseline and Week 16, and clinical data for 24 weeks are not reported in this summary and will be included in the manuscript.

Results Point of Contact

• Title: Senior Director GI Clinical Development
• Organization: Janssen-Cilag Ltd.

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen-Cilag Ltd. Clinical Trial

  Janssen-Cilag Ltd.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2018
• First Posted: December 20, 2018
• Study Start: December 20, 2018
• Primary Completion: August 19, 2022
• Study Completion: January 10, 2023
• Last Updated: April 29, 2025
• Results First Posted: September 13, 2023

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share

Locations

FR (7); NL (6); IT (6); US (28); KR (5); AU (2); GB (6); CZ (2); RU (4); DE (21); ES (15); SE (2)