Clinical trial NCT03107793: Study of Treat to Target Versus Routine Care Maintenance Strategies in Crohn's Disease Patients Treated With Ustekinumab
Official title: Study of Treat to Target Versus Routine Care Maintenance Strategies in Crohn's Disease Patients Treated With Ustekinumab
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Crohn Disease
Lead sponsor: Janssen-Cilag Ltd.
Sponsor class: INDUSTRY
First posted: 2017-04-11
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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
* Satisfy all inclusion criteria and none of the exclusion criteria specified in the main 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)

Primary outcomes:
measure: Percentage of Participants With Endoscopic Response at Week 48
timeFrame: Week 48
Secondary outcomes:
measure: Percentage of Participants With Endoscopic Response at Week 48 (Premature Drop-outs Excluded)
timeFrame: Week 48
measure: Percentage of Participants With Endoscopic Response at Week 48 (Last Observation Carried Forward [LOCF])
timeFrame: Week 48 (LOCF)
measure: Percentage of Participants With Clinical Response at Weeks 16, 48, and Endpoint (Week 48 [LOCF])
timeFrame: Weeks 16, 48, and Endpoint (Week 48 [LOCF])
measure: Percentage of Participants With Clinical Remission at Weeks 16, 48, and Endpoint (Week 48 [LOCF])
timeFrame: Weeks 16, 48, and Endpoint (Week 48 [LOCF])
measure: Percentage of Participants With Endoscopic Remission at Weeks 16, 48, and Endpoint (Week 48 [LOCF])
timeFrame: Weeks 16, 48, and Endpoint (Week 48 [LOCF])
measure: Percentage of Participants With Mucosal Healing at Weeks 16, 48, and Endpoint (Week 48 [LOCF])
timeFrame: Weeks 16, 48, and Endpoint (Week 48 [LOCF])
measure: Percentage of Participants With Corticosteroid-free Clinical Remission at Week 48 and Endpoint (Week 48 [LOCF])
timeFrame: Week 48 and Endpoint (Week 48 [LOCF])
measure: Percentage of Participants With Corticosteroid-free Endoscopic Response at Weeks 16, 48, and Endpoint (Week 48 [LOCF])
timeFrame: Weeks 16, 48, and Endpoint (Week 48 [LOCF])
measure: Change From Baseline in Serum C-reactive Protein (CRP)
timeFrame: Baseline, Weeks 16, 48 and Endpoint (Week 48 [LOCF]
measure: Change From Baseline in Fecal Calprotectin (FC)
timeFrame: Baseline, Weeks 16, 48 and Endpoint (Week 48 [LOCF])
measure: Percentage of Participants With Inflammatory Bowel Disease Questionnaire (IBDQ) Response
timeFrame: Weeks 16, 48, and Endpoint (Week 48 [LOCF])
measure: Percentage of Participants With 7-point Change From Baseline in Work Productivity and Activity Impairment (WPAI) Scores for Each Domain
timeFrame: Weeks 16, 48, and Endpoint (Week 48 [LOCF])
measure: Change From Baseline in IBDQ Score
timeFrame: Baseline, Weeks 16, 48, and Endpoint (Week 48 [LOCF])
measure: Change From Baseline in European Quality Of Life 5 Dimensions 5 Level (EQ-5D-5L) Visual Analog Scale (VAS) Score
timeFrame: Baseline, Weeks 16, 48, and Endpoint (Week 48 [LOCF])
measure: Changes From Baseline in Functional Assessment of Chronic Illness Therapy-fatigue (FACIT-F) Scale Score
timeFrame: Baseline, Weeks 16, 48, and Endpoint (Week 48 [LOCF])
measure: Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score
timeFrame: Baseline, Weeks 16, 48, and Endpoint (Week 48 [LOCF])
measure: Change From Baseline in WPAI Score
timeFrame: Baseline, Weeks 16, 48, and Endpoint (Week 48 [LOCF])
measure: Change From Baseline in Time Lost From Work
timeFrame: Baseline, Weeks 16, 48, and Endpoint (Week 48 [LOCF])
measure: Number of Participants With Adverse Events (AEs) That Occurred in Participants Administered With Ustekinumab up to Week 48
timeFrame: Up to Week 48
measure: Change From Baseline in Body Weight
timeFrame: Baseline, Weeks 16, 48, and Endpoint (Week 48 [LOCF])
measure: Change From Baseline in Body Mass Index (BMI)
timeFrame: Baseline, Weeks 16, 48, and Endpoint (Week 48 [LOCF])
measure: Change From Baseline in Blood Pressure
timeFrame: Baseline, Weeks 16, 48, and Endpoint (Week 48 [LOCF])
measure: Change From Baseline in Pulse Rate
timeFrame: Baseline, Weeks 16, 48, and Endpoint (Week 48 [LOCF])
Other outcomes:
Locations:
city: Antwerpen
country: Belgium
facility: GZA Ziekenhuizen
city: Bonheiden
country: Belgium
facility: Imelda Ziekenhuis
city: Brussel
country: Belgium
facility: UZ Brussel
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint Luc
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Gent
country: Belgium
facility: AZ Maria Middelares
city: Gent
country: Belgium
facility: UZ Gent
city: Kortrijk
country: Belgium
facility: Az Groeninge
city: Leuven
country: Belgium
facility: UZ Leuven
city: Liège
country: Belgium
facility: CHC MontLegia
city: Liège
country: Belgium
facility: CHU de Liege
city: Merksem
country: Belgium
facility: Algemeen Ziekenhuis Jan Palfijn Merksem
city: Oostende
country: Belgium
facility: AZ Damiaan
city: Hradec Kralove
country: Czechia
facility: Fakultni nemocnice Hradec Kralove
city: Hradec Kralove
country: Czechia
facility: Hepato-gastroenterologie HK, s.r.o.
city: Prague
country: Czechia
facility: EGK s.r.o. - Sanatorium sv. Anny
city: Prague
country: Czechia
facility: AXON Clinical s.r.o.
city: Prague
country: Czechia
facility: MEDIENDO s.r.o.
city: Praha 9
country: Czechia
facility: ISCARE a.s.
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
city: Aarhus C.
country: Denmark
facility: Aarhus Kommunehospital
city: København NV
country: Denmark
facility: Abdominalcenter K
city: Odense
country: Denmark
facility: Odense Universitetshospital
city: Silkeborg
country: Denmark
facility: Silkeborg Hospital
city: Vejle
country: Denmark
facility: Vejle Sygehus
city: Clichy
country: France
facility: Hopital Beaujon
city: La Tronche
country: France
facility: CHU Grenoble
city: Le Kremlin Bicêtre
country: France
facility: Hopital de Bicetre
city: Lille
country: France
facility: Hopital Claude Huriez
city: Montpellier
country: France
facility: CHU Saint Eloi
city: Nice
country: France
facility: CHU de Nice Hopital de l Archet
city: Paris
country: France
facility: Hopital Saint Louis
city: Pessac
country: France
facility: CHU Bordeaux
city: Pierre Bénite
country: France
facility: Hospices Civils de Lyon HCL
city: Saint Priest en jarez
country: France
facility: CHU Saint Etienne
city: Toulouse
country: France
facility: CHU Rangueil
city: Vandoeuvre les Nancy
country: France
facility: CHU-Nancy
city: Berlin
country: Germany
facility: Charite Universitatsmedizin Berlin Campus Virchow Klinikum
city: Frankfurt
country: Germany
facility: Agaplesion Frankfurter Diakonie Kliniken GmbH, Markus Krankenhaus
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Lueneburg
country: Germany
facility: Staedtisches Klinikum Lueneburg
city: Mannheim
country: Germany
facility: Universitaetsklinikum Mannheim
city: Muenster
country: Germany
facility: MVZ Portal10
city: Bari
country: Italy
facility: Policlinico di Bari Ospedale Giovanni XXIII
city: Bologna
country: Italy
facility: Policlinico Sant'Orsola Malpighi
city: Milano
country: Italy
facility: Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
city: Milano
country: Italy
facility: ASST Fatebenefratelli Sacco
city: Negrar (VR)
country: Italy
facility: Ospedale Classificato Equiparato Sacro Cuore Don Calabria di Negrar
city: Palermo
country: Italy
facility: Ospedale Villa Sofia-Cervello
city: RHO
country: Italy
facility: Azienda Ospedaliera G.Salvini Ospedale di Rho
city: Roma
country: Italy
facility: Azienda Ospedaliera San Camillo - Roma
city: Roma
country: Italy
facility: Fondazione Policlinico Gemelli Università Cattolica
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
city: San Donato Milanese
country: Italy
facility: IRCCS Policlinico San Donato
city: Torino
country: Italy
facility: AO Ordine Mauriziano
city: Udine
country: Italy
facility: Azienda Sanitaria Universitaria Integrata di Udine
city: Amersfoort
country: Netherlands
facility: Meander Medisch Centrum
city: Amsterdam
country: Netherlands
facility: AMC
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer Ziekenhuis
city: Gorinchem
country: Netherlands
facility: Rivas Zorggroep, Beatrixziekenhuis
city: Groningen
country: Netherlands
facility: UMCG
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Coimbra
country: Portugal
facility: Centro Hospitalar e Universitário de Coimbra, EPE
city: Faro
country: Portugal
facility: Centro Hospitalar e Universitário do Algarve
city: Lisboa
country: Portugal
facility: Centro Hospitalar Lisboa Central, EPE - Hospital Santo Antonio dos Capuchos
city: Lisboa
country: Portugal
facility: Centro Hospitalar Lisboa Norte EPE Hosp. Santa Maria
city: Porto
country: Portugal
facility: Centro Hospitalar do Porto, EPE
city: Porto
country: Portugal
facility: Centro Hospitalar de Sao Joao Epe
city: Viseu
country: Portugal
facility: Centro Hospitalar de Tondela Viseu, EPE
city: Banska Bystrica
country: Slovakia
facility: FNsP F.D.R. Banska Bystrica
city: Bardejov
country: Slovakia
facility: Gastroenterology Department GASTROMART s.r.o.
city: Bratislava
country: Slovakia
facility: Gastroenterology Center ASSIDUO
city: Bratislava
country: Slovakia
facility: University Hospital in Bratislava, St. Cyril and Method Hospital
city: Nitra
country: Slovakia
facility: KM Management spol. s r.o.
city: Presov
country: Slovakia
facility: GASTRO I. s.r.o.
city: Vranov nad Toplou
country: Slovakia
facility: Gastroenterology Department ENDOMED, s.r.o.
city: Alicante
country: Spain
facility: Hosp. Gral. Univ. de Alicante
city: Badalona
country: Spain
facility: Hosp. Univ. Germans Trias I Pujol
city: Barcelona
country: Spain
facility: Hosp Clinic de Barcelona
city: Córdoba
country: Spain
facility: Hosp Reina Sofia
city: El Ferrol
country: Spain
facility: Hosp. Arquitecto Marcide
city: L'Hospitalet de Llobregat
country: Spain
facility: Hosp. Univ. de Bellvitge
city: Madrid
country: Spain
facility: Hosp. Univ. de La Princesa
city: Madrid
country: Spain
facility: Hosp. Gral. Univ. Gregorio Maranon
city: Madrid
country: Spain
facility: Hosp. Univ. La Paz
city: Manises
country: Spain
facility: Hosp. de Manises
city: Palma de Mallorca
country: Spain
facility: Hosp. Univ. Son Espases
city: Sevilla
country: Spain
facility: Hosp. Virgen Del Rocio
city: Valencia
country: Spain
facility: Hosp. Clinico Univ. de Valencia
city: Valencia
country: Spain
facility: Hosp. Univ. I Politecni La Fe
city: Zaragoza
country: Spain
facility: Hosp. Clinico Univ. Lozano Blesa
city: Lund
country: Sweden
facility: Skane University Hospital
city: Solna
country: Sweden
facility: Karolinska University Hospital
city: Stockholm
country: Sweden
facility: Medicinkliniken
city: Stockholm
country: Sweden
facility: Danderyd Hospital
city: Belfast
country: United Kingdom
facility: Royal Victoria Hospital
city: Darlington
country: United Kingdom
facility: County Durham and Darlington NHS Foundation Trust
city: Dundee
country: United Kingdom
facility: Ninewells Hospital
city: Glasgow
country: United Kingdom
facility: Glasgow Royal Infirmary
city: London
country: United Kingdom
facility: Royal London Hospital
city: London
country: United Kingdom
facility: Guys St Thomas Hospital
city: London
country: United Kingdom
facility: Kings College Hospital NHS Trust
city: London
country: United Kingdom
facility: St George's University Hospital NHS Foundation Trust
city: Prescot
country: United Kingdom
facility: Whiston Hospital
city: Salford
country: United Kingdom
facility: Salford Royal NHS Foundation Trust
city: Southampton
country: United Kingdom
facility: Southampton University Hospital
city: Taunton
country: United Kingdom
facility: Musgrove Park Hospital
Study officials:
affiliation: Janssen-Cilag Ltd.
name: Janssen Cilag Ltd. Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.