A Study to Evaluate Efficacy and Safety of Ustekinumab Re-induction Therapy in Participants With Moderately to Severely Active Crohn's Disease
- Conditions
- Crohn Disease
- Interventions
- Drug: Placebo (IV)Drug: Placebo (SC)
- Registration Number
- NCT03782376
- Lead Sponsor
- Janssen-Cilag Ltd.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 215
Not provided
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 2: Ustekinumab (Continuous q8w SC maintenance) Ustekinumab 90 mg (SC) Group 2 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. Group 2: Ustekinumab (Continuous q8w SC maintenance) Placebo (IV) 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. Group 1: Ustekinumab (IV re-induction) Ustekinumab approximately 6 mg/kg (IV) 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. Group 1: Ustekinumab (IV re-induction) Placebo (SC) 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. Group 1: Ustekinumab (IV re-induction) Ustekinumab 90 mg (SC) Group 1 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.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Clinical Response at Week 16 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.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Clinical Laboratory Values for Chemistry (Alkaline Phosphatase, Alanine Transaminase [ALT], Aspartate Transaminase [AST]) Baseline, Weeks 8, 16, 24 Change from baseline in clinical laboratory values for chemistry (alkaline, ALT, AST) was reported.
Percentage of Participants With Clinical Remission at Week 8 Week 8 Percentage of participants with clinical remission at Week 8 were reported. Clinical remission was defined as CDAI score of \<150 points. CDAI is a validated multi-item measure of severity of illness derived as weighted sum of 8 different 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 remission, regardless of their CDAI score.
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 normalization at Week 16, among participants with elevated CRP and/or fCal at baseline were reported. Participants were considered to be normalized if at least one biomarker (fCal or CRP) was normalized. Normalized CRP=CRP value less than or equal to (\<=) 3 milligrams per liter(mg/L). Normalized fCal concentrations was defined as \<=250 micrograms per gram(mcg/g). When either CRP or FCal value was abnormal at baseline and value of same parameter normalizes at designated analysis timepoint, participants were considered to be normalized at designated analysis timepoint. 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 are considered not to be normalized. Participants who had insufficient data at designated analysis timepoint had their last value carried forward.
Percentage of Participants With Clinical Response at Week 24 Week 24 Clinical response was defined as a \>=100-point reduction from the baseline in CDAI score or a CDAI score \<150 point. The CDAI is a validated multi-item measure of severity of illness derived as a weighted sum of 8 different Crohn's disease-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 the participant on a diary card. In general, CDAI score ranges from 0 to approximately 600; higher score indicates 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.
Percentage of Participants With Normalization of C-reactive Protein (CRP) and/or Normalization of Fecal Calprotectin (fCal) Concentration at Week 24 Week 24 Percentage of participants with normalization at Week 24, among participants with elevated CRP and/or fCal at baseline were reported. Participants were considered to be normalized if at least one biomarker (fCal or CRP) was normalized. Normalized CRP=CRP value less than or equal to (\<=) 3 milligrams per liter(mg/L). Normalized fCal concentrations was defined as \<=250 micrograms per gram(mcg/g). When either CRP or FCal value was abnormal at baseline and value of same parameter normalizes at designated analysis timepoint, participants were considered to be normalized at designated analysis timepoint. 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 are considered not to be normalized. Participants who had insufficient data at designated analysis timepoint had their last value carried forward.
Percentage of Participants With Treatment-emergent Infections From baseline (Week 0) up to Week 36 Percentage of participants with treatment-emergent infections were reported. Any infection occurring at or after the initial administration of study agent through the end of the trial was considered to be treatment emergent.
Change From Baseline in Clinical Laboratory Values for Hematology (Hematocrit) Baseline, Weeks 8, 16, 24 Change from baseline in clinical laboratory values for hematology (hematocrit) was reported.
Change From Baseline in Clinical Laboratory Values for Hematology (Total White Blood Cell [WBC], Neutrophils, Absolute Lymphocyte, Eosinophils, Platelets) Baseline, Weeks 8, 16, 24 Change from baseline in clinical laboratory values for hematology (total WBC, neutrophils, absolute lymphocyte, eosinophils, platelets) was reported.
Change From Baseline in Clinical Laboratory Values for Chemistry (Total Bilirubin, Direct Bilirubin, Creatinine) Baseline, Weeks 8, 16, 24 Change from baseline in clinical laboratory values for chemistry (total bilirubin, direct bilirubin, creatinine) was reported.
Change From Baseline in Clinical Laboratory Values for Chemistry (Sodium, Potassium, Chloride, Blood Urea Nitrogen [BUN]/Urea, Calcium, Phosphate) Baseline, Weeks 8, 16, 24 Change from baseline in clinical laboratory values for chemistry (sodium, potassium, chloride, BUN/urea, calcium, phosphate) was reported.
Percentage of Participants With Clinical Remission at Week 16 Week 16 Percentage of participants with clinical remission at Week 16 were reported. Clinical remission was defined as CDAI score of \<150 points. CDAI is a validated multi-item measure of severity of illness derived as weighted sum of 8 different 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 remission, regardless of their CDAI score.
Percentage of Participants With Clinical Remission at Week 24 Week 24 Percentage of participants with clinical remission at Week 24 were reported. Clinical remission was defined as CDAI score of \<150 points. CDAI is a validated multi-item measure of severity of illness derived as weighted sum of 8 different 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 remission, regardless of their CDAI score.
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) From baseline (Week 0) up to Week 36 An adverse event was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An adverse event does not necessarily have a causal relationship with the treatment. TEAEs were adverse events with onset during the intervention phase or that were a consequence of a pre-existing condition that had worsened since baseline. Any AE occurring at or after the initial administration of study agent through the end of the trial was considered to be treatment emergent. In this outcome measure, TEAEs including all AEs irrespective of being serious or non-serious AE are reported.
Percentage of Participants With Clinical Response at Week 8 Week 8 Clinical response was defined as a \>=100-point reduction from the baseline in CDAI score or a CDAI score \<150 point. The CDAI is a validated multi-item measure of severity of illness derived as a weighted sum of 8 different 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 the participant on a diary card. In general, CDAI score ranges from 0 to approximately 600; higher score indicates 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.
Percentage of Participants With Treatment-emergent Serious Adverse Events (TESAEs) From baseline (Week 0) up to Week 36 A serious adverse event (SAE) was an adverse event resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; a suspected transmission of any infectious agent via a medicinal product; medically important. TESAEs were adverse events with onset during the intervention phase or that are a consequence of a pre-existing condition that had worsened since baseline. Any AE occurring at or after the initial administration of study agent through the end of the trial was considered to be treatment emergent.
Percentage of Participants With Treatment-emergent Serious Infections From baseline (Week 0) up to Week 36 Percentage of participants with treatment-emergent serious infections was reported. Any infection occurring at or after the initial administration of study agent through the end of the trial was considered to be treatment emergent.
Change From Baseline in Clinical Laboratory Values for Hematology (Hemoglobin) and Chemistry (Albumin, Total Protein) Baseline, Weeks 8, 16, 24 Change from baseline in clinical laboratory values for hematology (hemoglobin) and chemistry (albumin, total protein) was reported.
Trial Locations
- Locations (103)
Tyler Research Institute, LLC
🇺🇸Tyler, Texas, United States
CHRU Hopital de Pontchaillou
🇫🇷Rennes, France
CHU de Nancy_ Hopital Brabois
🇫🇷Vandoeuvre-les-Nancy, France
Klinikum Augsburg
🇩🇪Augsburg, Germany
GASTRO-Studien
🇩🇪Berlin, Germany
Charite - Universitaetsmedizin Berlin (CCM)
🇩🇪Berlin, Germany
Medizinisches Versorgungszentrum (MVZ) Dachau
🇩🇪Dachau, Germany
University Hospital Dresden
🇩🇪Dresden, Germany
Agaplesion Frankfurter Diakonie Kliniken GmbH, Markus Krankenhaus
🇩🇪Frankfurt, Germany
Universitatsklinikum Frankfurt/ Medizinische Klinik 1
🇩🇪Frankfurt, Germany
Universitatsklinikum Freiburg
🇩🇪Freiburg, Germany
Städtisches Krankenhaus Martha-Maria Halle-Dölau gGmbH
🇩🇪Halle, Germany
Hamburgisches Forschungsinstitut fuer CED, HaFCED e.K.
🇩🇪Hamburg, Germany
Gastroenterologie Opernstrasse
🇩🇪Kassel, Germany
Universitatsklinikum Schleswig Holstein Kiel
🇩🇪Kiel, Germany
Staedtisches Klinikum Lueneburg
🇩🇪Lueneburg, Germany
Universitätsklinikum Otto-von-Guericke-Universität Magdeburg
🇩🇪Magdeburg, Germany
Medizinische Fakultät Mannheim der Universität Heidelberg
🇩🇪Mannheim, Germany
Gastroenterologische Gemeinschaftspraxis Minden
🇩🇪Minden, Germany
Klinikum der Universitaet Muenchen
🇩🇪Muenchen, Germany
Praxis Dr. med. Ulf Helwig
🇩🇪Oldenburg, Germany
Zentrum für Gastroenterologie Saar MVZ GmbH
🇩🇪Saarbrücken, Germany
Universitaetsklinik Tuebingen
🇩🇪Tübingen, Germany
Universitaetsklinikum Ulm, Klinik fuer Innere Medizin II
🇩🇪Ulm, Germany
Pennine Acute Hospitals-Fairfield General Hospital
🇬🇧Bury, United Kingdom
Hepato-gastroenterologie HK, s.r.o.
🇨🇿Hradec Kralove, Czechia
ISCARE a.s.
🇨🇿Praha 9, Czechia
Hopital Beaujon
🇫🇷Clichy, France
CHRU de Lille Hopital Claude Huriez
🇫🇷Lille, France
CHRU Montpellier - Hopital Saint-Eloi
🇫🇷Montpellier, France
CHU Hopital Saint Antoine
🇫🇷Paris cedex 12, France
Hospices Civils de Lyon HCL
🇫🇷Pierre Bénite, France
Sint Franciscus Gasthuis
🇳🇱Rotterdam, Netherlands
Irkutsk State Medical Academy of Postgraduate Education
🇷🇺Irkutsk, Russian Federation
Olla-Med, Llc
🇷🇺Moscow, Russian Federation
City Clinical Hospital #31
🇷🇺St. Petersburg, Russian Federation
Corporacio Sanitari Parc Tauli
🇪🇸Sabadell, Spain
Hosp Clinico Univ de Salamanca
🇪🇸Salamanca, Spain
Hosp. Univ. Marques de Valdecilla
🇪🇸Santander, Spain
Hosp. Clinico Univ. de Valencia
🇪🇸Valencia, Spain
Hosp. Alvaro Cunqueiro
🇪🇸Vigo, Spain
Hosp. Clinico Univ. Lozano Blesa
🇪🇸Zaragoza, Spain
Hosp. Univ. Miguel Servet
🇪🇸Zaragoza, Spain
Gastromottagningen
🇸🇪Stockholm, Sweden
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
🇮🇹Milano, Italy
Ospedale Villa Sofia-Cervello
🇮🇹Palermo, Italy
Azienda Ospedaliera G.Salvini Ospedale di Rho
🇮🇹RHO, Italy
Fondazione Policlinico Gemelli Università Cattolica
🇮🇹Roma, Italy
Istituto Clinico Humanitas
🇮🇹Rozzano, Italy
AO Ordine Mauriziano
🇮🇹Torino, Italy
Inje University Haeundae Paik Hospital
🇰🇷Busan, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
KyungHee University Hospital
🇰🇷Seoul, Korea, Republic of
Onze Lieve Vrouwe Gasthuis
🇳🇱Amsterdam, Netherlands
Leiden University Medical Center
🇳🇱Leiden, Netherlands
Maastricht Universitair Medisch Centrum
🇳🇱Maastricht, Netherlands
Radboudumc
🇳🇱Nijmegen, Netherlands
Erasmus MC
🇳🇱Rotterdam, Netherlands
GBUZ Respublican Clinical Hospital n.a. GG Kuvatova
🇷🇺Ufa, Russian Federation
Hosp. Univ. Fundacion Alcorcon
🇪🇸Alcorcón, Spain
Hosp. Arquitecto Marcide
🇪🇸Ferrol, Spain
Hosp. Gral. Univ. Gregorio Maranon
🇪🇸Madrid, Spain
Hosp. Univ. La Paz
🇪🇸Madrid, Spain
Hosp. Univ. Virgen de La Arrixaca
🇪🇸Murcia, Spain
Hosp Virgen de La Victoria
🇪🇸Málaga, Spain
Hosp. de Navarra
🇪🇸Pamplona, Spain
Hosp. Montecelo
🇪🇸Pontevedra, Spain
Florida Hospital Tampa
🇺🇸Tampa, Florida, United States
Peak Gastroenterology Associates
🇺🇸Colorado Springs, Colorado, United States
University of California, San Diego
🇺🇸La Jolla, California, United States
Medizinische Universitaet Wien
🇦🇹Wien, Austria
Florida Research Network, LLC
🇺🇸Gainesville, Florida, United States
Mayo Clinic Jacksonville
🇺🇸Jacksonville, Florida, United States
Advent Health
🇺🇸Orlando, Florida, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Atlanta Gastroenterology Associates, (AGA) LLC - Emory Saint Joseph's
🇺🇸Atlanta, Georgia, United States
Atlanta Gastroenterology Specialists
🇺🇸Suwanee, Georgia, United States
University of Kentucky Chandler Medical Center
🇺🇸Lexington, Kentucky, United States
Chevy Chase Clinical Research
🇺🇸Chevy Chase, Maryland, United States
Brigham And Women's Hospital
🇺🇸Boston, Massachusetts, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
Washington University School Of Medicine
🇺🇸Saint Louis, Missouri, United States
Mount Sinai School of Medicine
🇺🇸New York, New York, United States
Ohio State University Hospital
🇺🇸Hilliard, Ohio, United States
Northshore Gastroenterology Research, LLC
🇺🇸Westlake, Ohio, United States
Oklahoma Digestive Disease Specialists
🇺🇸Oklahoma City, Oklahoma, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Texas Digestive Disease Consultants
🇺🇸Cedar Park, Texas, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
Houston Methodist Hospital
🇺🇸Houston, Texas, United States
Gastroenterology Research of America, LLC
🇺🇸San Antonio, Texas, United States
Virginia Mason Medical Center
🇺🇸Seattle, Washington, United States
University of Washington
🇺🇸Seattle, Washington, United States
Washington Gastroenterology, PLLC
🇺🇸Tacoma, Washington, United States
Krankenhaus der Barmherzigen Brüder
🇦🇹Wien, Austria
Gloucestershire Hospitals NHS Foundation Trust - Cheltenham
🇬🇧Cheltenham, United Kingdom
Royal Devon & Exeter Hospital
🇬🇧Exeter, United Kingdom
King's College Hospital NHS Foundation Trust
🇬🇧London, United Kingdom
St George's Hospital
🇬🇧London, United Kingdom
Southampton University Hospitals NHS Trust
🇬🇧Southampton, United Kingdom