Clinical trial NCT03782376: A Study to Evaluate Efficacy and Safety of Ustekinumab Re-induction Therapy in Participants With Moderately to Severely Active Crohn's Disease
Official title: A Phase 3b, Randomized, Double-blind, Multicenter Study to Evaluate the Safety and Efficacy of Intravenous Re-induction Therapy With Ustekinumab in Patients With Moderately to Severely Active Crohn's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Crohn Disease
Lead sponsor: Janssen-Cilag Ltd.
Sponsor class: INDUSTRY
First posted: 2018-12-20
Enrollment: 215
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 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.

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

Primary outcomes:
measure: Percentage of Participants With Clinical Response at Week 16
timeFrame: Week 16
Secondary outcomes:
measure: Percentage of Participants With Clinical Remission at Week 16
timeFrame: Week 16
measure: Percentage of Participants With Clinical Response at Week 8
timeFrame: Week 8
measure: Percentage of Participants With Clinical Remission at Week 8
timeFrame: Week 8
measure: Percentage of Participants With Normalization of C-reactive Protein (CRP) and/or Normalization of Fecal Calprotectin (fCal) Concentration at Week 16
timeFrame: Week 16
measure: Percentage of Participants With Clinical Remission at Week 24
timeFrame: Week 24
measure: Percentage of Participants With Clinical Response at Week 24
timeFrame: Week 24
measure: Percentage of Participants With Normalization of C-reactive Protein (CRP) and/or Normalization of Fecal Calprotectin (fCal) Concentration at Week 24
timeFrame: Week 24
measure: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: From baseline (Week 0) up to Week 36
measure: Percentage of Participants With Treatment-emergent Serious Adverse Events (TESAEs)
timeFrame: From baseline (Week 0) up to Week 36
measure: Percentage of Participants With Treatment-emergent Infections
timeFrame: From baseline (Week 0) up to Week 36
measure: Percentage of Participants With Treatment-emergent Serious Infections
timeFrame: From baseline (Week 0) up to Week 36
measure: Change From Baseline in Clinical Laboratory Values for Hematology (Hemoglobin) and Chemistry (Albumin, Total Protein)
timeFrame: Baseline, Weeks 8, 16, 24
measure: Change From Baseline in Clinical Laboratory Values for Hematology (Hematocrit)
timeFrame: Baseline, Weeks 8, 16, 24
measure: Change From Baseline in Clinical Laboratory Values for Hematology (Total White Blood Cell [WBC], Neutrophils, Absolute Lymphocyte, Eosinophils, Platelets)
timeFrame: Baseline, Weeks 8, 16, 24
measure: Change From Baseline in Clinical Laboratory Values for Chemistry (Alkaline Phosphatase, Alanine Transaminase [ALT], Aspartate Transaminase [AST])
timeFrame: Baseline, Weeks 8, 16, 24
measure: Change From Baseline in Clinical Laboratory Values for Chemistry (Total Bilirubin, Direct Bilirubin, Creatinine)
timeFrame: Baseline, Weeks 8, 16, 24
measure: Change From Baseline in Clinical Laboratory Values for Chemistry (Sodium, Potassium, Chloride, Blood Urea Nitrogen [BUN]/Urea, Calcium, Phosphate)
timeFrame: Baseline, Weeks 8, 16, 24
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California, San Diego
state: California
city: Colorado Springs
country: United States
facility: Peak Gastroenterology Associates
state: Colorado
city: Gainesville
country: United States
facility: Florida Research Network, LLC
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville
state: Florida
city: Orlando
country: United States
facility: Advent Health
state: Florida
city: Tampa
country: United States
facility: Florida Hospital Tampa
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Atlanta
country: United States
facility: Atlanta Gastroenterology Associates, (AGA) LLC - Emory Saint Joseph's
state: Georgia
city: Suwanee
country: United States
facility: Atlanta Gastroenterology Specialists
state: Georgia
city: Lexington
country: United States
facility: University of Kentucky Chandler Medical Center
state: Kentucky
city: Chevy Chase
country: United States
facility: Chevy Chase Clinical Research
state: Maryland
city: Boston
country: United States
facility: Brigham And Women's Hospital
state: Massachusetts
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Saint Louis
country: United States
facility: Washington University School Of Medicine
state: Missouri
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Hilliard
country: United States
facility: Ohio State University Hospital
state: Ohio
city: Westlake
country: United States
facility: Northshore Gastroenterology Research, LLC
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Digestive Disease Specialists
state: Oklahoma
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Cedar Park
country: United States
facility: Texas Digestive Disease Consultants
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: San Antonio
country: United States
facility: Gastroenterology Research of America, LLC
state: Texas
city: Tyler
country: United States
facility: Tyler Research Institute, LLC
state: Texas
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Tacoma
country: United States
facility: Washington Gastroenterology, PLLC
state: Washington
city: Wien
country: Austria
facility: Krankenhaus der Barmherzigen Brüder
city: Wien
country: Austria
facility: Medizinische Universitaet Wien
city: Hradec Kralove
country: Czechia
facility: Hepato-gastroenterologie HK, s.r.o.
city: Praha 9
country: Czechia
facility: ISCARE a.s.
city: Clichy
country: France
facility: Hopital Beaujon
city: Lille
country: France
facility: CHRU de Lille Hopital Claude Huriez
city: Montpellier
country: France
facility: CHRU Montpellier - Hopital Saint-Eloi
city: Paris cedex 12
country: France
facility: CHU Hopital Saint Antoine
city: Pierre Bénite
country: France
facility: Hospices Civils de Lyon HCL
city: Rennes
country: France
facility: CHRU Hopital de Pontchaillou
city: Vandoeuvre-les-Nancy
country: France
facility: CHU de Nancy_ Hopital Brabois
city: Augsburg
country: Germany
facility: Klinikum Augsburg
city: Berlin
country: Germany
facility: GASTRO-Studien
city: Berlin
country: Germany
facility: Charite - Universitaetsmedizin Berlin (CCM)
city: Dachau
country: Germany
facility: Medizinisches Versorgungszentrum (MVZ) Dachau
city: Dresden
country: Germany
facility: University Hospital Dresden
city: Frankfurt
country: Germany
facility: Agaplesion Frankfurter Diakonie Kliniken GmbH, Markus Krankenhaus
city: Frankfurt
country: Germany
facility: Universitatsklinikum Frankfurt/ Medizinische Klinik 1
city: Freiburg
country: Germany
facility: Universitatsklinikum Freiburg
city: Halle
country: Germany
facility: Städtisches Krankenhaus Martha-Maria Halle-Dölau gGmbH
city: Hamburg
country: Germany
facility: Hamburgisches Forschungsinstitut fuer CED, HaFCED e.K.
city: Kassel
country: Germany
facility: Gastroenterologie Opernstrasse
city: Kiel
country: Germany
facility: Universitatsklinikum Schleswig Holstein Kiel
city: Lueneburg
country: Germany
facility: Staedtisches Klinikum Lueneburg
city: Magdeburg
country: Germany
facility: Universitätsklinikum Otto-von-Guericke-Universität Magdeburg
city: Mannheim
country: Germany
facility: Medizinische Fakultät Mannheim der Universität Heidelberg
city: Minden
country: Germany
facility: Gastroenterologische Gemeinschaftspraxis Minden
city: Muenchen
country: Germany
facility: Klinikum der Universitaet Muenchen
city: Oldenburg
country: Germany
facility: Praxis Dr. med. Ulf Helwig
city: Saarbrücken
country: Germany
facility: Zentrum für Gastroenterologie Saar MVZ GmbH
city: Tübingen
country: Germany
facility: Universitaetsklinik Tuebingen
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm, Klinik fuer Innere Medizin II
city: Milano
country: Italy
facility: Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
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: Fondazione Policlinico Gemelli Università Cattolica
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
city: Torino
country: Italy
facility: AO Ordine Mauriziano
city: Busan
country: Korea, Republic of
facility: Inje University Haeundae Paik Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: KyungHee University Hospital
city: Amsterdam
country: Netherlands
facility: Onze Lieve Vrouwe Gasthuis
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Maastricht
country: Netherlands
facility: Maastricht Universitair Medisch Centrum
city: Nijmegen
country: Netherlands
facility: Radboudumc
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Rotterdam
country: Netherlands
facility: Sint Franciscus Gasthuis
city: Irkutsk
country: Russian Federation
facility: Irkutsk State Medical Academy of Postgraduate Education
city: Moscow
country: Russian Federation
facility: Olla-Med, Llc
city: St. Petersburg
country: Russian Federation
facility: City Clinical Hospital #31
city: Ufa
country: Russian Federation
facility: GBUZ Respublican Clinical Hospital n.a. GG Kuvatova
city: Alcorcón
country: Spain
facility: Hosp. Univ. Fundacion Alcorcon
city: Ferrol
country: Spain
facility: Hosp. Arquitecto Marcide
city: Madrid
country: Spain
facility: Hosp. Gral. Univ. Gregorio Maranon
city: Madrid
country: Spain
facility: Hosp. Univ. La Paz
city: Murcia
country: Spain
facility: Hosp. Univ. Virgen de La Arrixaca
city: Málaga
country: Spain
facility: Hosp Virgen de La Victoria
city: Pamplona
country: Spain
facility: Hosp. de Navarra
city: Pontevedra
country: Spain
facility: Hosp. Montecelo
city: Sabadell
country: Spain
facility: Corporacio Sanitari Parc Tauli
city: Salamanca
country: Spain
facility: Hosp Clinico Univ de Salamanca
city: Santander
country: Spain
facility: Hosp. Univ. Marques de Valdecilla
city: Valencia
country: Spain
facility: Hosp. Clinico Univ. de Valencia
city: Vigo
country: Spain
facility: Hosp. Alvaro Cunqueiro
city: Zaragoza
country: Spain
facility: Hosp. Clinico Univ. Lozano Blesa
city: Zaragoza
country: Spain
facility: Hosp. Univ. Miguel Servet
city: Malmö
country: Sweden
facility: Gastromottagningen
city: Stockholm
country: Sweden
facility: Gastromottagningen
city: Bury
country: United Kingdom
facility: Pennine Acute Hospitals-Fairfield General Hospital
city: Cheltenham
country: United Kingdom
facility: Gloucestershire Hospitals NHS Foundation Trust - Cheltenham
city: Exeter
country: United Kingdom
facility: Royal Devon & Exeter Hospital
city: London
country: United Kingdom
facility: King's College Hospital NHS Foundation Trust
city: London
country: United Kingdom
facility: St George's Hospital
city: Southampton
country: United Kingdom
facility: Southampton University Hospitals NHS Trust
Study officials:
affiliation: Janssen-Cilag Ltd.
name: Janssen-Cilag Ltd. Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.