A Study of Ustekinumab in Pediatric Participants With Moderately to Severely Active Crohn's Disease
- Registration Number
- NCT04673357
- Lead Sponsor
- Janssen Research & Development, LLC
- Brief Summary
The purpose of this study is to evaluate the efficacy of ustekinumab dosing in inducing clinical remission (Global) and in maintaining clinical remission (US); to evaluate the safety profile and ustekinumab exposure (pharmacokinetics \[PK\]) in pediatric participants with moderately to severely active Crohn's disease.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 101
- Have Crohn's disease or fistulizing Crohn's disease with active colitis, ileitis, or ileocolitis, confirmed at any time in the past by endoscopy and histology
- Must have moderately to severely active Crohn's disease (as defined by a baseline Pediatric Crohn's Disease Activity Index [PCDAI] score greater than [>] 30); have ileocolonoscopy with evidence of active Crohn's disease defined as presence of ulceration (which is equal to Simple Endoscopic Score for Crohn's disease [SES-CD] score greater than or equals to [>=] 3) during screening into this study. The ileocolonoscopy procedure must occur within approximately 3 weeks prior to the administration of study intervention at Week 0 (Induction Period). A video ileocolonoscopy recorded within 3 months prior to the Week 0 (Induction Period) visit may be used in case of rescreening of a participant who had an ileocolonoscopy but failed the initial screening for another reason, on a case-by-case basis, after consultation with the sponsor. If unable to evaluate ulceration due to stricture or inadequate bowel preparation, at least one of the following criteria may instead be applied: an abnormal C-reactive protein (CRP) (> 0.3 milligram per deciliter [mg/dL] or 3.0 milligram per liter [mg/L] at screening) or; fecal calprotectin of >= 250 milligram per kilogram [mg/kg] or >= 250 microgram per gram [mcg/g] at screening
- If receiving enteral nutrition, must have been on a stable regimen for at least 2 weeks prior to induction week 0 (Week I-0)
- Females of childbearing potential must have a negative highly sensitive urine pregnancy test at screening and at Week I-0 prior to study intervention administration
- Has complications of Crohn's disease such as symptomatic strictures or stenosis, short gut syndrome, or any other manifestation that might be anticipated to require surgery, that could preclude the use of the PCDAI to assess response to therapy or would possibly confound the ability to assess the effect of treatment with ustekinumab
- Have a history of latent or active granulomatous infection, histoplasmosis, or coccidioidomycosis, or have had a nontuberculous mycobacterial infection prior to screening
- Presence or history of any malignancy including presence or history of lymphoproliferative disease including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy of unusual size or location (example, nodes in the posterior triangle of the neck, infraclavicular, epitrochlear, or periaortic areas), and monoclonal gammopathy of undetermined significance, or clinically significant hepatomegaly or splenomegaly
- Have a history of moderate or severe progressive or uncontrolled liver or renal insufficiency; or significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, psychiatric (including suicidality), or metabolic disturbances
- Received an investigational intervention including any investigational vaccines or used an invasive investigational medical device within 3 months before the planned first dose of study intervention or is currently enrolled in an investigational study; receipt of an investigational vaccine for Coronavirus Disease 2019 (COVID-19) is not an automatic exclusion criterion
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Open- Label Ustekinumab Intravenous (IV): Induction Period Ustekinumab All participants will receive a single IV administration of ustekinumab at induction Week 0 (I-0) based on body surface area (BSA) (milligram per meter square \[mg/m\^2\]) or weight-tiered induction dose (milligram per kilogram \[mg/kg\]). Ustekinumab Subcutaneous (SC) Every 8 Weeks (q8w): Maintenance Period Ustekinumab Participants will receive SC administration of ustekinumab q8w based on BSA (mg/m\^2) or weight-tiered induction dose (mg/kg) at maintenance weeks (Weeks M)-0, M-8, M-16, M-24, M 32, and M-40 and matching placebo at Weeks M-12 and M-36 to maintain the blind. Ustekinumab Subcutaneous (SC) Every 8 Weeks (q8w): Maintenance Period Placebo Participants will receive SC administration of ustekinumab q8w based on BSA (mg/m\^2) or weight-tiered induction dose (mg/kg) at maintenance weeks (Weeks M)-0, M-8, M-16, M-24, M 32, and M-40 and matching placebo at Weeks M-12 and M-36 to maintain the blind. Ustekinumab SC Every 12 Weeks (q12w): Maintenance Period Ustekinumab Participants will receive SC administration of ustekinumab q12w based on BSA (mg/m\^2) or weight-tiered induction dose (mg/kg) at Weeks M-0, M-12, M-24, M-36 and matching placebo at Weeks M-8, M-16, M-32, and M-40 to maintain the blind. Ustekinumab SC Every 12 Weeks (q12w): Maintenance Period Placebo Participants will receive SC administration of ustekinumab q12w based on BSA (mg/m\^2) or weight-tiered induction dose (mg/kg) at Weeks M-0, M-12, M-24, M-36 and matching placebo at Weeks M-8, M-16, M-32, and M-40 to maintain the blind.
- Primary Outcome Measures
Name Time Method Number of Participants with Clinical Remission at Maintenance Week 44 Week 44 (Maintenance Period) Number of participants with clinical remission in maintenance period will be assessed. This will be assessed among participants who are in clinical response at induction week-8 (I-8). Clinical remission is defined as having a PCDAI score \<= 10 points. PCDAI is an index used to measure disease activity of pediatric patients with Crohn's Disease assessing abdominal pain, stool frequency, patient functioning, hematocrit, erythrocyte sedimentation rate, albumin, weight, height, abdominal tenderness or mass, perirectal disease, and extraintestinal manifestations. It ranges from 0 to 100; higher scores indicate more active disease.
Number of Participants with AEs of Interest Up to Week 74 Number of participants with AEs of interest (any newly identified malignancy, or case of active tuberculosis \[TB\], or opportunistic infection occurring after the first administration of study intervention\[s\]) will be reported.
Number of Participants with Abnormalities in Clinical Laboratory Parameters Up to Week 52 Number of participants with abnormalities in clinical laboratory parameters (such as hematology and chemistry) will be reported.
Number of Participants with Reactions Temporally Associated with Intravenous (IV) Infusion (Induction Period) Up to Week 8 (Induction period) Number of participants with reactions temporally associated with IV infusion in induction period will be reported.
Number of Participants with Clinical Remission at Induction Week 8 Week 8 Number of participants with clinical remission in induction period will be assessed. Clinical remission is defined as having a Pediatric Crohn's Disease Activity Index (PCDAI) score less than or equal to (\<=) 10 points. PCDAI is an index used to measure disease activity of pediatric patients with Crohn's Disease assessing abdominal pain, stool frequency, patient functioning, hematocrit, erythrocyte sedimentation rate, albumin, weight, height, abdominal tenderness or mass, perirectal disease, and extraintestinal manifestations. It ranges from 0 to 100; higher scores indicate more active disease.
Number of Participants with Adverse Events (AEs) Up to Week 74 An AE can be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non investigational) product, whether or not related to that medicinal (investigational or non investigational) product.
Number of Participants with Serious Adverse Events (SAEs) Up to Week 74 A SAE is any untoward medical occurrence that at any dose: results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is a suspected transmission of any infectious agent via a medicinal product; is medically important.
Number of Participants with AEs leading to Discontinuation of Study Intervention Up to Week 74 Number of participants with AEs leading to discontinuation of study intervention will be reported.
Serum Ustekinumab Concentrations Up to Week 52 Serum ustekinumab concentrations will be reported.
Number of Participants with Subcutaneous (SC) Injection-Site Reactions (Maintenance Period) Up to Week 44 (Maintenance period) Number of participants with SC injection-site reactions in maintenance period will be reported.
- Secondary Outcome Measures
Name Time Method Number of Participants with Clinical Remission as Assessed by short Pediatric Crohn's Disease Activity Index (sPCDAI) Week 6 (Induction period) Number of participants with clinical remission in induction period as assessed by sPCDAI will be reported. Clinical remission is defined as PCDAI score and sPCDAI score \<= 10 points.
Number of Participants with Endoscopic Response as Assessed by Simplified Endoscopic Score-Crohn's Disease (SES-CD) Week 8 (Maintenance period) Number of participants with endoscopic response as assessed by SES-CD in maintenance period will be reported. Endoscopic response is defined as a reduction in SES-CD score of \>= 50 percent (%) or SES-CD score \<= 2 in participants with a baseline SES-CD score of \>= 3. The SES-CD score is based on the evaluation of 4 endoscopic components (presence/size of ulcers, proportion of mucosal surface covered by ulcers, proportion of mucosal surface affected by any other lesions, and presence/type of narrowing/strictures) across 5 ileocolonic segments. Each endoscopic component is scored from 0 to 3 for each segment, and a total score is derived from the sum of all the component scores (range, 0 to 60).
Number of Participants with Clinical Response as Assessed by sPCDAI Week 6 (Induction period) Number of participants with clinical response in induction period as assessed by sPCDAI will be reported. Clinical response is defined as a reduction from baseline in the PCDAI score of greater than or equal to (\>=) 12.5 points with a total PCDAI score not more than 30.
Number of Participants with Clinical Remission at Week 44 (Maintenance Period) who are in Clinical Remission at Week 8 (Induction Period) Week 44 (Maintenance Period) Number of participants with clinical remission at Week 44 (maintenance period) who are in clinical remission at Week 8 (induction period) will be reported.
Number of Participants with Clinical Remission Week 44 (Maintenance period) Number of participants with clinical remission in maintenance period will be reported.
Number of Participants with Clinical Response Week 44 (Maintenance period) Number of participants with clinical response in maintenance period will be reported.
Number of Participants with Endoscopic Response as Assessed by SES-CD Week 44 (Maintenance period) Number of participants with endoscopic response as assessed by SES-CD in maintenance period will be reported. Endoscopic response is defined as a reduction in SES-CD score of \>= 50 percent (%) or SES-CD score \<= 2 in participants with a baseline SES-CD score of \>= 3. The SES-CD score is based on the evaluation of 4 endoscopic components (presence/size of ulcers, proportion of mucosal surface covered by ulcers, proportion of mucosal surface affected by any other lesions, and presence/type of narrowing/strictures) across 5 ileocolonic segments. Each endoscopic component is scored from 0 to 3 for each segment, and a total score is derived from the sum of all the component scores (range, 0 to 60).
Number of Participants with Corticosteroid-free Clinical Remission Week 44 (Maintenance period) Number of participants with corticosteroid-free clinical remission in maintenance period will be reported. Corticosteroid-free clinical remission is PCDAI score \<= 10 points and not receiving corticosteroids for at least 90 days prior to Week 44.
Trial Locations
- Locations (53)
Nemours DuPont Hospital for Children
🇺🇸Wilmington, Delaware, United States
Children's Center for Digestive Health Care
🇺🇸Atlanta, Georgia, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Morristown Memorial Hospital
🇺🇸Morristown, New Jersey, United States
Levine Childrens at Atrium Health
🇺🇸Charlotte, North Carolina, United States
University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
Penn State Hershey Children's Hospital
🇺🇸Hershey, Pennsylvania, United States
Cook Childrens Medical Center
🇺🇸Fort Worth, Texas, United States
Pediatric Specialists Of Virginia
🇺🇸Fairfax, Virginia, United States
Universitair Kinderziekenhuis Koningin Fabiola
🇧🇪Brussel, Belgium
Cliniques Universitaires Saint Luc
🇧🇪Bruxelles, Belgium
UZ Gent
🇧🇪Gent, Belgium
UZ Brussel
🇧🇪Jette, Belgium
UZ Leuven
🇧🇪Leuven, Belgium
Universitätsklinikum Aachen
🇩🇪Aachen, Germany
Charite-Universitätsmedizin Berlin - Berlin
🇩🇪Berlin, Germany
Universitatsklinikum Essen
🇩🇪Essen, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Dr. von Haunersches Kinderspital
🇩🇪Munich, Germany
KUNO Klinik St. Hedwig
🇩🇪Regensburg, Germany
Universitatsklinikum Ulm
🇩🇪Ulm, Germany
Semmelweis Egyetem
🇭🇺Budapest, Hungary
Debreceni Egyetem Klinikai Kozpont
🇭🇺Debrecen, Hungary
Borsod Abauj Zemplen Varmegyei Kozponti Korhaz es Egyetemi Oktato Korhaz
🇭🇺Miskolc, Hungary
Szabolcs Szatmar Bereg Varmegyei Oktatokorhaz
🇭🇺Nyiregyhaza, Hungary
Szegedi Tudományegyetem, Gyermekgyógyászati Klinika és Gyermekegészségügyi Centrum
🇭🇺Szeged, Hungary
Yitzhak Shamir Medical Center
🇮🇱Be'er Ya'akov, Israel
Carmel Medical Center
🇮🇱Haifa, Israel
Korczowski Bartosz Gabinet Lekarski
🇵🇱Rzeszow, Poland
Instytut Pomnik Centrum Zdrowia Dziecka
🇵🇱Warszawa, Poland
Kazan State Medical University
🇷🇺Kazan, Russian Federation
Russian National Research Medical University named after N.I.Pirogov
🇷🇺Moscow, Russian Federation
Privolzhsky Research Medical University of Ministry of Health of Russian Federation
🇷🇺Nizhny Novgorod, Russian Federation
Yaroslavl Regional Children's Clinical Hospital
🇷🇺Yaroslavl, Russian Federation
Birmingham Children's Hospital
🇬🇧Birmingham, United Kingdom
University Hospitals Bristol and Weston NHS Foundation Trust
🇬🇧Bristol, United Kingdom
Shaare Zedek Medical Center
🇮🇱Jerusalem, Israel
Juntendo University Hospital
🇯🇵Bunkyo Ku, Japan
Gunma University Hospital
🇯🇵Gunma, Japan
Kindai University Nara Hospital
🇯🇵Ikoma, Japan
Kurume University Hospital
🇯🇵Kurume, Japan
Saitama Childrens Medical Center
🇯🇵Saitama shi, Japan
Miyagi Children's Hospital
🇯🇵Sendai, Japan
Jichi Medical University Hospital
🇯🇵Shimotsuke, Japan
Mie University Hospital
🇯🇵Tsu, Japan
Szpital im. M. Kopernika
🇵🇱Gdansk, Poland
Uniwersytecki Szpital Dzieciecy w Krakowie
🇵🇱Krakow, Poland
Schneider Children's Medical Center
🇮🇱Petah Tikva, Israel
National Center for Child Health and Development
🇯🇵Setagaya Ku, Japan
WIP Warsaw IBD Point Profesor Kierkus
🇵🇱Warszawa, Poland
Cambridge University Hospitals NHS Foundation Trust
🇬🇧Cambridge, United Kingdom
Royal Hospital for Children and Young People
🇬🇧Edinburgh, United Kingdom
Royal London Hospital
🇬🇧London, United Kingdom