NCT03107793

Brief Summary

The purpose of this study is to evaluate the efficacy of a treat to target strategy coupled with early endoscopic assessment versus a clinically driven (routine care) approach in achieving endoscopic response.

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
500

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Apr 2017

Typical duration for phase_3

Geographic Reach
12 countries

107 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 28, 2017

Completed
14 days until next milestone

First Posted

Study publicly available on registry

April 11, 2017

Completed
8 days until next milestone

Study Start

First participant enrolled

April 19, 2017

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 30, 2020

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

May 19, 2021

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

July 20, 2021

Completed
Last Updated

April 29, 2025

Status Verified

April 1, 2025

Enrollment Period

3 years

First QC Date

March 28, 2017

Results QC Date

April 28, 2021

Last Update Submit

April 25, 2025

Conditions

Outcome Measures

Primary Outcomes (1)

  • Percentage of Participants With Endoscopic Response at Week 48

    Endoscopic response defined as showing a reduction from baseline in simple endoscopic score for Crohn's disease (SES-CD) of greater than or equal to (\>=) 50 percent (%). SES-CD is a validated instrument reflecting an endoscopist global appraisal of mucosal lesions in Crohn's disease. SES-CD grades lesions by location (5 bowel segments: ileum, right colon, transverse colon, left colon, and rectum) using 4 endoscopic variables: ulcer size, extent of ulcerated surface, extent of affected surface, and presence/type of narrowing. Total SES-CD is sum of 4 variables for all 5 bowel segments. Scores range from 0-60 with higher scores indicating more severe disease. Randomized participants who stopped treatment before reaching Week 48 due to any reason, or participants without endoscopic data at Week 48 were analyzed as nonresponders.

    Week 48

Secondary Outcomes (23)

  • Percentage of Participants With Endoscopic Response at Week 48 (Premature Drop-outs Excluded)

    Week 48

  • Percentage of Participants With Endoscopic Response at Week 48 (Last Observation Carried Forward [LOCF])

    Week 48 (LOCF)

  • Percentage of Participants With Clinical Response at Weeks 16, 48, and Endpoint (Week 48 [LOCF])

    Weeks 16, 48, and Endpoint (Week 48 [LOCF])

  • Percentage of Participants With Clinical Remission at Weeks 16, 48, and Endpoint (Week 48 [LOCF])

    Weeks 16, 48, and Endpoint (Week 48 [LOCF])

  • Percentage of Participants With Endoscopic Remission at Weeks 16, 48, and Endpoint (Week 48 [LOCF])

    Weeks 16, 48, and Endpoint (Week 48 [LOCF])

  • +18 more secondary outcomes

Study Arms (4)

All Participants

EXPERIMENTAL

At Week (Wk) 0, all eligible participants will initiate intravenous (IV) induction treatment with ustekinumab (UST) on a weight-tiered basis at a dose of approximately 6 milligram per kilogram (mg/kg). At Week 8, all participants will receive a 90 milligram (mg) subcutaneous (SC) injection of ustekinumab. At Week 16, participants who do not achieve a Crohn's Disease Activity Index (CDAI) improvement of greater than or equal to (\>=) 70 points versus Week 0 (CDAI 70) will leave the study. Remaining participants will be randomized in a 1:1 ratio to either one of two arms for open label maintenance treatment up to Week 48: the treat to target arm or the routine care arm. From Week 48, participants will continue ustekinumab treatment in the study extension period, up to Week 104. Dosing frequency will be adjusted in the extension period for the participants failing to meet the treatment target.

Drug: Ustekinumab

Routine Care Arm

EXPERIMENTAL

In the routine care arm, assessment visits will be scheduled according to the timing of maintenance treatment injections up to Week 48, which will be in compliance with the EU SmPC for ustekinumab for the treatment of Crohn's disease, in which dosing every 12 weeks is recommended. At Week 16, (that is, 8 weeks after the first SC dose) participants continuing in the study will have demonstrated a CDAI-70 response. Nonetheless, participants who have not shown adequate response based on the investigator's judgment may receive a second SC dose at Week 16. During the routine care maintenance treatment period, in case of clinical worsening reported by the participant, consistent with disease flare in the investigator's judgment, clinical assessments of disease flare will be performed at the investigator's discretion.

Drug: Ustekinumab

Treat to Target (T2T) Arm

EXPERIMENTAL

UST maintenance treatment assignment will be based on centrally-read colonoscopy (at Wk16). Participants with \<25% improvement in SES-CD score at Wk16 will be assigned to Q8 (8-weekly) treatment and will receive UST 90mg SC at Wk16. In contrast, participants with \>=25% improvement in SES-CD score at Wk16 will be assigned to Q12 treatment and will receive next UST dose (90 mg SC) at Wk20. At assessment visits (from Wk24 for participants assigned to the Q8 regimen or from Wk20 for the Q12 group) UST maintenance treatment (up to Wk 48) will be directed by T2T assessments. Participants meeting target will continue with same UST dosing frequency. The dosing frequency will be optimized for all participants failing to meet the target at assessment visit. Those previously on Q12 regimens will be adjusted to Q8 dosing; those previously on Q8 regimens will be adjusted to Q4 dosing. Participants subsequently failing to meet the target will not be able to adjust further and will leave the study.

Drug: Ustekinumab

Exploratory Extension period: From Week 48 to Week 104

EXPERIMENTAL

At Week 48, dose de-escalation will be implemented for participants with both endoscopic remission (SES-CD score \<=2) and corticosteroid-free clinical remission of at least 16 weeks duration. Participants receiving 12 weekly dosing frequency (Q12) ustekinumab will maintain this dosing frequency. Participants with either clinical remission or endoscopic remission, but not both, at Week 48 will continue with same dosing frequency or de-escalate provided maintenance of corticosteroid-free clinical remission and biomarker remission at 2 consecutive visits. Participants with neither corticosteroid-free clinical remission nor endoscopic remission will escalate dose or leave study if already on 4 weekly dosing frequency (Q4) dose. If neither clinical remission nor biomarker remission is evident at the next visit, participant will leave study. Later in the extension period, only those who achieve corticosteroid-free clinical remission and biomarker remission will undergo dose de-escalation.

Drug: Ustekinumab

Interventions

Participants will receive IV induction treatment with ustekinumab on a weight-tiered basis at a dose of approximately 6 milligram per kilogram (mg/kg) IV. At Week 8, all participants will receive a 90 mg SC injection of ustekinumab. During the routine care maintenance treatment period, in case of clinical worsening reported by the participant, consistent with disease flare in the investigator's judgment, clinical assessments of disease flare will be performed at the investigator's discretion.

All ParticipantsExploratory Extension period: From Week 48 to Week 104Routine Care ArmTreat to Target (T2T) Arm

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Main Study:
  • Have active, moderate to severe, ileal and/or colonic Crohn's disease, demonstrated by: baseline CDAI score of greater than or equal to (\>=) 220 and less than equal to (\<=) 450, and endoscopy with evidence of active Crohn's disease (defined as simple endoscopic score for Crohn's disease \[SES-CD\] score \>=3 excluding the contribution of the narrowing component score) obtained within the 5 week screening period. A prior endoscopy may be used only if obtained within 3 months prior to baseline (Week 0), in which case the prior endoscopy must be centrally read again and SES-CD calculated based on this second, centralized read-out
  • Has had an inadequate response with, lost response to, was intolerant to, or had medical contraindications to either conventional therapy, or one previous biologic therapy approved for the treatment of Crohn's disease in the countries in which the study is conducted
  • Are eligible according to tuberculosis (TB) infection screening criteria
  • Must sign an informed consent form (ICF) or their legally acceptable representative if applicable must sign) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study.
  • Sub-study:
  • Be enrolled into the main study at a participating site
  • Sign a separate ICF indicating that they understand the purpose of and procedures required for this sub-study and are willing to participate in the sub-study

You may not qualify if:

  • Main Study:
  • Has 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 Crohn's Disease Activity Index (CDAI) to assess response to therapy, or would possibly confound the ability to assess the effect of treatment with ustekinumab
  • Has had any kind of bowel resection within 6 months prior to baseline
  • Has a draining (i.e, functioning) stoma or ostomy
  • Has received more than one previous biologic therapy approved for the treatment of Crohn's disease in the countries in which the study is conducted
  • Sub-study:
  • Obesity or other characteristics considered likely to preclude intestinal ultrasound (IUS) visualization of the affected bowel segment
  • Normal bowel wall thickness (BWT) (that is, \<=2.0 millimeter \[mm\] for the terminal ileum; \<=3.0 mm for the colon) for all bowel segments at baseline (Week 0)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (107)

GZA Ziekenhuizen

Antwerp, 2018, Belgium

Location

Imelda Ziekenhuis

Bonheiden, 2820, Belgium

Location

UZ Brussel

Brussels, 1090, Belgium

Location

Cliniques Universitaires Saint Luc

Brussels, 1200, Belgium

Location

Universitair Ziekenhuis Antwerpen

Edegem, 2650, Belgium

Location

AZ Maria Middelares

Ghent, 9000, Belgium

Location

UZ Gent

Ghent, 9000, Belgium

Location

Az Groeninge

Kortrijk, 8500, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

CHC MontLegia

Liège, 4000, Belgium

Location

CHU de Liege

Liège, 4000, Belgium

Location

Algemeen Ziekenhuis Jan Palfijn Merksem

Merksem, 2170, Belgium

Location

AZ Damiaan

Ostend, 8400, Belgium

Location

Fakultni nemocnice Hradec Kralove

Hradec Králové, 500 05, Czechia

Location

Hepato-gastroenterologie HK, s.r.o.

Hradec Králové, 500 12, Czechia

Location

EGK s.r.o. - Sanatorium sv. Anny

Prague, 13000, Czechia

Location

AXON Clinical s.r.o.

Prague, 15000, Czechia

Location

MEDIENDO s.r.o.

Prague, 186 00, Czechia

Location

ISCARE a.s.

Prague, 190 00, Czechia

Location

Aalborg University Hospital

Aalborg, 9100, Denmark

Location

Aarhus Kommunehospital

Aarhus C, DK-8000, Denmark

Location

Abdominalcenter K

København NV, 2400, Denmark

Location

Odense Universitetshospital

Odense, 5000, Denmark

Location

Silkeborg Hospital

Silkeborg, 8600, Denmark

Location

Vejle Sygehus

Vejle, 7100, Denmark

Location

Hopital Beaujon

Clichy, 92110, France

Location

CHU Grenoble

La Tronche, 38700, France

Location

Hopital de Bicetre

Le Kremlin-Bicêtre, 94270, France

Location

Hopital Claude Huriez

Lille, 59037, France

Location

CHU Saint Eloi

Montpellier, 34295, France

Location

CHU de Nice Hopital de l Archet

Nice, 6202, France

Location

Hopital Saint Louis

Paris, 75010, France

Location

CHU Bordeaux

Pessac, 33600, France

Location

Hospices Civils de Lyon HCL

Pierre-Bénite, 69495, France

Location

CHU Saint Etienne

Saint-Priest-en-Jarez, 42270, France

Location

CHU Rangueil

Toulouse, 31059, France

Location

CHU-Nancy

Vandœuvre-lès-Nancy, 54511, France

Location

Charite Universitatsmedizin Berlin Campus Virchow Klinikum

Berlin, 13353, Germany

Location

Agaplesion Frankfurter Diakonie Kliniken GmbH, Markus Krankenhaus

Frankfurt, 60431, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Staedtisches Klinikum Lueneburg

Lüneburg, 21339, Germany

Location

Universitaetsklinikum Mannheim

Mannheim, 68167, Germany

Location

MVZ Portal10

Münster, 48151, Germany

Location

Policlinico di Bari Ospedale Giovanni XXIII

Bari, Italy

Location

Policlinico Sant'Orsola Malpighi

Bologna, 40138, Italy

Location

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

ASST Fatebenefratelli Sacco

Milan, 20157, Italy

Location

Ospedale Classificato Equiparato Sacro Cuore Don Calabria di Negrar

Negrar (VR), 37024, Italy

Location

Ospedale Villa Sofia-Cervello

Palermo, 90146, Italy

Location

Azienda Ospedaliera G.Salvini Ospedale di Rho

Rho, Italy

Location

Azienda Ospedaliera San Camillo - Roma

Roma, 00152, Italy

Location

Fondazione Policlinico Gemelli Università Cattolica

Roma, 168, Italy

Location

Istituto Clinico Humanitas

Rozzano, 20089, Italy

Location

IRCCS Policlinico San Donato

San Donato Milanese, 20097, Italy

Location

AO Ordine Mauriziano

Torino, 10128, Italy

Location

Azienda Sanitaria Universitaria Integrata di Udine

Udine, 33100, Italy

Location

Meander Medisch Centrum

Amersfoort, 3813 TZ, Netherlands

Location

AMC

Amsterdam, 1105 AZ, Netherlands

Location

Albert Schweitzer Ziekenhuis

Dordrecht, 3318 AT, Netherlands

Location

Rivas Zorggroep, Beatrixziekenhuis

Gorinchem, 4200 AB, Netherlands

Location

UMCG

Groningen, 9713 GZ, Netherlands

Location

Erasmus MC

Rotterdam, 3015 CE, Netherlands

Location

Centro Hospitalar e Universitário de Coimbra, EPE

Coimbra, 3000-075, Portugal

Location

Centro Hospitalar e Universitário do Algarve

Faro, 8000-386, Portugal

Location

Centro Hospitalar Lisboa Central, EPE - Hospital Santo Antonio dos Capuchos

Lisbon, 1169-050, Portugal

Location

Centro Hospitalar Lisboa Norte EPE Hosp. Santa Maria

Lisbon, 1649-035, Portugal

Location

Centro Hospitalar do Porto, EPE

Porto, 4099 001, Portugal

Location

Centro Hospitalar de Sao Joao Epe

Porto, 4200 319, Portugal

Location

Centro Hospitalar de Tondela Viseu, EPE

Viseu, 3504-509, Portugal

Location

FNsP F.D.R. Banska Bystrica

Banská Bystrica, 975 17, Slovakia

Location

Gastroenterology Department GASTROMART s.r.o.

Bardejov, 085 01, Slovakia

Location

Gastroenterology Center ASSIDUO

Bratislava, 811 08, Slovakia

Location

University Hospital in Bratislava, St. Cyril and Method Hospital

Bratislava, 851 07, Slovakia

Location

KM Management spol. s r.o.

Nitra, 949 01, Slovakia

Location

GASTRO I. s.r.o.

Prešov, 080 01, Slovakia

Location

Gastroenterology Department ENDOMED, s.r.o.

Vranov nad Topľou, 093 01, Slovakia

Location

Hosp. Gral. Univ. de Alicante

Alicante, 3010, Spain

Location

Hosp. Univ. Germans Trias I Pujol

Badalona, 08916, Spain

Location

Hosp Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hosp Reina Sofia

Córdoba, 14004, Spain

Location

Hosp. Arquitecto Marcide

Ferrol, 15405, Spain

Location

Hosp. Univ. de Bellvitge

L'Hospitalet de Llobregat, 08907, Spain

Location

Hosp. Univ. de La Princesa

Madrid, 28006, Spain

Location

Hosp. Gral. Univ. Gregorio Maranon

Madrid, 28007, Spain

Location

Hosp. Univ. La Paz

Madrid, 28046, Spain

Location

Hosp. de Manises

Manises, 46940, Spain

Location

Hosp. Univ. Son Espases

Palma de Mallorca, 07120, Spain

Location

Hosp. Virgen Del Rocio

Seville, 41013, Spain

Location

Hosp. Clinico Univ. de Valencia

Valencia, 46010, Spain

Location

Hosp. Univ. I Politecni La Fe

Valencia, 46026, Spain

Location

Hosp. Clinico Univ. Lozano Blesa

Zaragoza, 50009, Spain

Location

Skane University Hospital

Lund, SE-22185, Sweden

Location

Karolinska University Hospital

Solna, SE-17176, Sweden

Location

Medicinkliniken

Stockholm, 11281, Sweden

Location

Danderyd Hospital

Stockholm, SE-11828, Sweden

Location

Royal Victoria Hospital

Belfast, BT12 6BA, United Kingdom

Location

County Durham and Darlington NHS Foundation Trust

Darlington, DL3 6HX, United Kingdom

Location

Ninewells Hospital

Dundee, DD1 9SY, United Kingdom

Location

Glasgow Royal Infirmary

Glasgow, G4 0SF, United Kingdom

Location

Royal London Hospital

London, E1 1BB, United Kingdom

Location

Guys St Thomas Hospital

London, SE1 7EH, United Kingdom

Location

Kings College Hospital NHS Trust

London, SE5 9RS, United Kingdom

Location

St George's University Hospital NHS Foundation Trust

London, SW17 0QT, United Kingdom

Location

Whiston Hospital

Prescot, L35 5DR, United Kingdom

Location

Salford Royal NHS Foundation Trust

Salford, M6 8HD, United Kingdom

Location

Southampton University Hospital

Southampton, SO16 6YD, United Kingdom

Location

Musgrove Park Hospital

Taunton, TA1 5DA, United Kingdom

Location

Related Publications (4)

  • 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.

  • Peyrin-Biroulet L, Vermeire S, D'Haens G, Panes J, Dignass A, Magro F, Nazar M, Le Bars M, Lahaye M, Ni L, Bravata I, Lavie F, Daperno M, Lukas M, Armuzzi A, Lowenberg M, Gaya DR, Danese S. Clinical trial: Clinical and endoscopic outcomes with ustekinumab in patients with Crohn's disease: Results from the long-term extension period of STARDUST. Aliment Pharmacol Ther. 2024 Jan;59(2):175-185. doi: 10.1111/apt.17751. Epub 2023 Nov 30.

  • Kucharzik T, Wilkens R, D'Agostino MA, Maconi G, Le Bars M, Lahaye M, Bravata I, Nazar M, Ni L, Ercole E, Allocca M, Machkova N, de Voogd FAE, Palmela C, Vaughan R, Maaser C; STARDUST Intestinal Ultrasound study group. Early Ultrasound Response and Progressive Transmural Remission After Treatment With Ustekinumab in Crohn's Disease. Clin Gastroenterol Hepatol. 2023 Jan;21(1):153-163.e12. doi: 10.1016/j.cgh.2022.05.055. Epub 2022 Jul 14.

  • Danese S, Vermeire S, D'Haens G, Panes J, Dignass A, Magro F, Nazar M, Le Bars M, Lahaye M, Ni L, Bravata I, Lavie F, Daperno M, Lukas M, Armuzzi A, Lowenberg M, Gaya DR, Peyrin-Biroulet L; STARDUST study group. Treat to target versus standard of care for patients with Crohn's disease treated with ustekinumab (STARDUST): an open-label, multicentre, randomised phase 3b trial. Lancet Gastroenterol Hepatol. 2022 Apr;7(4):294-306. doi: 10.1016/S2468-1253(21)00474-X. Epub 2022 Feb 1.

MeSH Terms

Conditions

Crohn Disease

Interventions

Ustekinumab

Condition Hierarchy (Ancestors)

Inflammatory Bowel DiseasesGastroenteritisGastrointestinal DiseasesDigestive System DiseasesIntestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Results Point of Contact

Title
European Medicines Agency (EMEA) Advisor-Immunology
Organization
Janssen-Cilag International N.V.

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
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 28, 2017

First Posted

April 11, 2017

Study Start

April 19, 2017

Primary Completion

April 30, 2020

Study Completion

July 20, 2021

Last Updated

April 29, 2025

Results First Posted

May 19, 2021

Record last verified: 2025-04

Locations