Study of Treat to Target Versus Routine Care Maintenance Strategies in Crohn's Disease Patients Treated With Ustekinumab

NCT ID: NCT03107793

Last Updated: 2025-04-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 500 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-04-19
• Study Completion Date: 2021-07-20

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.

Detailed Description

Study investigates benefit of treat to target maintenance treatment strategy versus routine care to test hypothesis that 'treat to target' ustekinumab (UST) maintenance treatment strategy coupled with early endoscopic assessment will result in higher endoscopic response rate after 48 weeks of treatment, compared to pragmatic maintenance treatment strategy. It consists of screening (5 weeks); treatment period (Week 0 to 48); extension period (Weeks 48 to 104) and safety follow up visit (16 weeks after last dose). Participants will be given an option to enter ultrasound sub-study to assess intestinal ultrasound (IUS) parameters indicating transmural changes in response to treatment with UST in participants with Crohn's disease. Study treatment will be unaffected by participation in sub-study which is optional for participants of main study.

Conditions

Crohn Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

All Participants

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.

Group Type: EXPERIMENTAL

Ustekinumab

Intervention Type: DRUG

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.

Routine Care Arm

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.

Group Type: EXPERIMENTAL

Ustekinumab

Intervention Type: DRUG

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.

Treat to Target (T2T) Arm

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.

Group Type: EXPERIMENTAL

Ustekinumab

Intervention Type: DRUG

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.

Exploratory Extension period: From Week 48 to Week 104

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.

Group Type: EXPERIMENTAL

Ustekinumab

Intervention Type: DRUG

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.

Interventions

Ustekinumab

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

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
• 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 prior to baseline, or 8 weeks prior to 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
• 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)

• 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

GZA Ziekenhuizen

Antwerp, , Belgium

Imelda Ziekenhuis

Bonheiden, , Belgium

UZ Brussel

Brussels, , Belgium

Cliniques Universitaires Saint Luc

Brussels, , Belgium

Universitair Ziekenhuis Antwerpen

Edegem, , Belgium

AZ Maria Middelares

Ghent, , Belgium

UZ Gent

Ghent, , Belgium

Az Groeninge

Kortrijk, , Belgium

UZ Leuven

Leuven, , Belgium

CHC MontLegia

Liège, , Belgium

CHU de Liege

Liège, , Belgium

Algemeen Ziekenhuis Jan Palfijn Merksem

Merksem, , Belgium

AZ Damiaan

Ostend, , Belgium

Fakultni nemocnice Hradec Kralove

Hradec Králové, , Czechia

Hepato-gastroenterologie HK, s.r.o.

Hradec Králové, , Czechia

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

Prague, , Czechia

AXON Clinical s.r.o.

Prague, , Czechia

MEDIENDO s.r.o.

Prague, , Czechia

ISCARE a.s.

Prague, , Czechia

Aalborg University Hospital

Aalborg, , Denmark

Aarhus Kommunehospital

Aarhus C, , Denmark

Abdominalcenter K

København NV, , Denmark

Odense Universitetshospital

Odense, , Denmark

Silkeborg Hospital

Silkeborg, , Denmark

Vejle Sygehus

Vejle, , Denmark

Hopital Beaujon

Clichy, , France

CHU Grenoble

La Tronche, , France

Hopital de Bicetre

Le Kremlin-Bicêtre, , France

Hopital Claude Huriez

Lille, , France

CHU Saint Eloi

Montpellier, , France

CHU de Nice Hopital de l Archet

Nice, , France

Hopital Saint Louis

Paris, , France

CHU Bordeaux

Pessac, , France

Hospices Civils de Lyon HCL

Pierre-Bénite, , France

CHU Saint Etienne

Saint-Priest-en-Jarez, , France

CHU Rangueil

Toulouse, , France

CHU-Nancy

Vandœuvre-lès-Nancy, , France

Charite Universitatsmedizin Berlin Campus Virchow Klinikum

Berlin, , Germany

Agaplesion Frankfurter Diakonie Kliniken GmbH, Markus Krankenhaus

Frankfurt, , Germany

Medizinische Hochschule Hannover

Hanover, , Germany

Staedtisches Klinikum Lueneburg

Lüneburg, , Germany

Universitaetsklinikum Mannheim

Mannheim, , Germany

MVZ Portal10

Münster, , Germany

Policlinico di Bari Ospedale Giovanni XXIII

Bari, , Italy

Policlinico Sant'Orsola Malpighi

Bologna, , Italy

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico

Milan, , Italy

ASST Fatebenefratelli Sacco

Milan, , Italy

Ospedale Classificato Equiparato Sacro Cuore Don Calabria di Negrar

Negrar (VR), , Italy

Ospedale Villa Sofia-Cervello

Palermo, , Italy

Azienda Ospedaliera G.Salvini Ospedale di Rho

Rho, , Italy

Azienda Ospedaliera San Camillo - Roma

Roma, , Italy

Fondazione Policlinico Gemelli Università Cattolica

Roma, , Italy

Istituto Clinico Humanitas

Rozzano, , Italy

IRCCS Policlinico San Donato

San Donato Milanese, , Italy

AO Ordine Mauriziano

Torino, , Italy

Azienda Sanitaria Universitaria Integrata di Udine

Udine, , Italy

Meander Medisch Centrum

Amersfoort, , Netherlands

AMC

Amsterdam, , Netherlands

Albert Schweitzer Ziekenhuis

Dordrecht, , Netherlands

Rivas Zorggroep, Beatrixziekenhuis

Gorinchem, , Netherlands

UMCG

Groningen, , Netherlands

Erasmus MC

Rotterdam, , Netherlands

Centro Hospitalar e Universitário de Coimbra, EPE

Coimbra, , Portugal

Centro Hospitalar e Universitário do Algarve

Faro, , Portugal

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

Lisbon, , Portugal

Centro Hospitalar Lisboa Norte EPE Hosp. Santa Maria

Lisbon, , Portugal

Centro Hospitalar do Porto, EPE

Porto, , Portugal

Centro Hospitalar de Sao Joao Epe

Porto, , Portugal

Centro Hospitalar de Tondela Viseu, EPE

Viseu, , Portugal

FNsP F.D.R. Banska Bystrica

Banská Bystrica, , Slovakia

Gastroenterology Department GASTROMART s.r.o.

Bardejov, , Slovakia

Gastroenterology Center ASSIDUO

Bratislava, , Slovakia

University Hospital in Bratislava, St. Cyril and Method Hospital

Bratislava, , Slovakia

KM Management spol. s r.o.

Nitra, , Slovakia

GASTRO I. s.r.o.

Prešov, , Slovakia

Gastroenterology Department ENDOMED, s.r.o.

Vranov nad Topľou, , Slovakia

Hosp. Gral. Univ. de Alicante

Alicante, , Spain

Hosp. Univ. Germans Trias I Pujol

Badalona, , Spain

Hosp Clinic de Barcelona

Barcelona, , Spain

Hosp Reina Sofia

Córdoba, , Spain

Hosp. Arquitecto Marcide

Ferrol, , Spain

Hosp. Univ. de Bellvitge

L'Hospitalet de Llobregat, , Spain

Hosp. Univ. de La Princesa

Madrid, , Spain

Hosp. Gral. Univ. Gregorio Maranon

Madrid, , Spain

Hosp. Univ. La Paz

Madrid, , Spain

Hosp. de Manises

Manises, , Spain

Hosp. Univ. Son Espases

Palma de Mallorca, , Spain

Hosp. Virgen Del Rocio

Seville, , Spain

Hosp. Clinico Univ. de Valencia

Valencia, , Spain

Hosp. Univ. I Politecni La Fe

Valencia, , Spain

Hosp. Clinico Univ. Lozano Blesa

Zaragoza, , Spain

Skane University Hospital

Lund, , Sweden

Karolinska University Hospital

Solna, , Sweden

Medicinkliniken

Stockholm, , Sweden

Danderyd Hospital

Stockholm, , Sweden

Royal Victoria Hospital

Belfast, , United Kingdom

County Durham and Darlington NHS Foundation Trust

Darlington, , United Kingdom

Ninewells Hospital

Dundee, , United Kingdom

Glasgow Royal Infirmary

Glasgow, , United Kingdom

Royal London Hospital

London, , United Kingdom

Guys St Thomas Hospital

London, , United Kingdom

Kings College Hospital NHS Trust

London, , United Kingdom

St George's University Hospital NHS Foundation Trust

London, , United Kingdom

Whiston Hospital

Prescot, , United Kingdom

Salford Royal NHS Foundation Trust

Salford, , United Kingdom

Southampton University Hospital

Southampton, , United Kingdom

Musgrove Park Hospital

Taunton, , United Kingdom

Countries

Belgium; Czechia; Denmark; France; Germany; Italy; Netherlands; Portugal; Slovakia; 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)

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.

Reference Type: DERIVED

PMID: 38036946 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35842121 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35120656 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-002918-43

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CNTO1275CRD3005

Identifier Type: OTHER

Identifier Source: secondary_id

CR108276

Identifier Type: -

Identifier Source: org_study_id