Crohn Disease
Conditions
Keywords
Pediatric
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.
Interventions
DRUGUstekinumab
Ustekinumab will be administered intravenously in induction period and subcutaneously in maintenance period.
DRUGPlacebo
Matching placebo will be administered as SC injection.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Induction period is an open-label period and maintenance period is a double-blind period.
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Global Outcome Measure: Percentage of Participants With Clinical Remission at Induction Week 8 (Week I-8) | Induction Week 8 (Week I-8) | Clinical remission was defined as a Pediatric Crohn's Disease Activity Index (PCDAI) score \<=10. The 11-item PCDAI covered five general disease activity domains: symptom history scores (3 items: abdominal pain, stool frequency, and general well-being); laboratory scores (3 items: hematocrit \[HCT\], erythrocyte sedimentation rate \[ESR\], Albumin); growth scores (2 items: weight and height); physical examination scores (2 items: abdomen and perirectal disease); and extraintestinal manifestations. The category of severity for each index item is assigned a score: 0=normal;5=mild abnormality; 10= severe abnormality. For hematocrit and erythrocyte SR, the maximum score =5. For albumin level, the maximum score = 10. All items were summed to derive the total score. The total PCDAI score ranged from 0 to 100, with higher scores indicating greater disease activity. |
| US-specific Outcome Measure: Percentage of Participants With Clinical Remission at Maintenance Week 44 | Maintenance Week 44 (Study Week 52) | Clinical remission was defined as a Pediatric Crohn's Disease Activity Index (PCDAI) score \<=10. The 11-item PCDAI covered five general disease activity domains: symptom history scores (3 items: abdominal pain, stool frequency, and general well-being); laboratory scores (3 items: HCT, ESR, Albumin); growth scores (2 items: weight and height); physical examination scores (2 items: abdomen and perirectal disease); and extraintestinal manifestations. The category of severity for each index item was assigned a score: 0=normal;5=mild abnormality; 10= severe abnormality. For hematocrit and erythrocyte SR, the maximum score= 5. For albumin level, the maximum score= 10. All items were summed to derive the total score. The total PCDAI score ranged from 0 to 100, with higher scores indicating greater disease activity. |
| Global and US-specific Outcome Measures: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Induction Period: From induction Week 0 up to induction Week 8; Maintenance Period: From Maintenance Week 0 (Study Week 8) up to Maintenance Week 44 (Study Week 52) | Number of participants with TEAEs were reported. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE did not necessarily have a causal relationship with the intervention. TEAEs were defined as AEs occurring at or after the initial administration of the study intervention. |
| Global and US-specific Outcome Measures: Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) | Induction Period: From induction Week 0 up to induction Week 8; Maintenance Period: From Maintenance Week 0 (Study Week 8) up to Maintenance Week 44 (Study Week 52) | Number of participants with TESAEs was reported. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE did not necessarily have a causal relationship with the intervention. An SAE was an AE 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; or congenital anomaly. TESAEs were defined as any SAE occurring at or after the initial administration of the study intervention. |
| Global and US-specific Outcome Measures: Number of Participants With AEs Leading to Discontinuation of Study Intervention | Induction Period: From induction Week 0 up to induction Week 8; Maintenance Period: From Maintenance Week 0 (Study Week 8) up to Maintenance Week 40 (Study Week 48) | Number of participants with AEs leading to discontinuation of study intervention were reported. |
| Global and US-specific Outcome Measures: Number of Participants With AEs of Special Interest (AESI) | Induction Period: From induction Week 0 up to induction Week 8; Maintenance Period: From Maintenance Week 0 (Study Week 8) up to Maintenance Week 44 (Study Week 52) | An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE did not necessarily have a causal relationship with the intervention. AESI were defined as any newly identified malignancy, or case of active TB, or opportunistic infection occurring after the first administration of study intervention. |
| Global and US-specific Outcome Measures: Number of Participants With Abnormalities in Clinical Laboratory Parameters: Hematology | Induction Period: From induction Week 0 up to induction Week 8; Maintenance Period: From Maintenance Week 0 (Study Week 8) up to Maintenance Week 44 (Study Week 52) | Number of participants with abnormalities in clinical laboratory parameters (hematology) were reported. It included hemoglobin (Hb). Grades 0-4 were based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), where Grade 0 was normal, Grade 1 was mild, Grade 2 was moderate, Grade 3 was severe or medically significant but not immediately life-threatening, and Grade 4 was life-threatening consequences. Higher grades showed more severe abnormalities. Only abnormalities where atleast one participant had data are reported. Inc = increased, Dec= decreased. |
| Global and US-specific Outcome Measures: Number of Participants With Abnormalities in Clinical Laboratory Parameters: Chemistry | Induction Period: From induction Week 0 up to induction Week 8; Maintenance Period: From Maintenance Week 0 (Study Week 8) up to Maintenance Week 44 (Study Week 52) | Number of participants with abnormalities in clinical laboratory parameters were reported. It included chemistry measures: alanine aminotransferase (ALT), aspartate aminotransferase (AST),blood bilirubin (BB). Grades 0-4 were based on NCI-CTCAE version 5.0, where Grade 0 was Normal, Grade 1 was mild, Grade 2 was moderate, Grade 3 was severe or medically significant but not immediately life-threatening, and Grade 4 was life-threatening consequences. Higher grades showed more severe abnormalities. Only abnormalities where at least one participant had data are reported. Inc = increased, Dec= decreased. |
| Global and US-specific Outcome Measures: Number of Participants With Reactions Temporally Associated With Intravenous (IV) Infusion (Induction Period) and Subcutaneous (SC) Injection-Site Reactions (Maintenance Period) | Induction Period: From induction Week 0 up to induction Week 8; Maintenance Period: From Maintenance Week 0 (Study Week 8) up to Maintenance Week 44 (Study Week 52) | Number of participants with reactions temporally associated with intravenous (IV) infusion (Induction Period) and subcutaneous (SC) Injection-Site Reactions (Maintenance Period) were reported. |
| Global and US-specific Outcome Measures: Serum Ustekinumab Concentrations | Induction Period: Week 0 (Pre-infusion), Week I-0 (1-hour post infusion), Week I-3, Week I-6, and Week I-8; Maintenance Period: Week M-4, Week M-8, Week M-12, Week M-16, Week M-24, Week M-32, Week M-36 and Week M-44 | Serum ustekinumab concentrations were reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Global Outcome Measure: Percentage of Participants With Clinical Remission at Induction Week 6 as Assessed by Short Pediatric Crohn's Disease Activity Index (sPCDAI) | Induction Week 6 (Week I-6) | Clinical remission was defined as a short Pediatric Crohn's Disease Activity Index (sPCDAI) score \<=10. The sPCDAI was composed of six components: abdominal pain, stool frequency, patient general well-being, body weight, abdominal examination (abdominal mass and tenderness), and extraintestinal manifestations. Each component was assigned a score of 0, 5, 10, or 20, depending on the severity of findings, with higher scores indicating greater disease activity, while lower scores (closer to 0) reflected clinical remission or minimal disease activity. Individual component scores were summed to derive the total sPCDAI score, which ranged from 0 to 90. Higher score indicate greater severity. The sPCDAI score was calculated only when \>=3 of the 6 components were available. |
| Global Outcome Measure: Percentage of Participants With Clinical Response at Induction Week 8 | Induction Week 8 | Assessment of response in children with Crohn's disease was evaluated using the PCDAI. Clinical response was defined as a reduction from baseline of \>=12.5 points in the PCDAI score, calculated by summing weighted scores from 11 items across five domains: symptom history (abdominal pain, stool frequency, and general well-being); laboratory scores (hematocrit, erythrocyte sedimentation rate, and albumin); growth scores (weight and height); physical examination scores (abdominal and perirectal disease); and extraintestinal manifestations. Each index item was assigned a severity score of 0 (normal), 5 (mild abnormality), or 10 (severe abnormality). For HCT and ESR, maximum score was 5, and for albumin level, maximum score was 10. The total PCDAI score ranged from 0 to 100, with higher scores indicating greater disease activity. Lower PCDAI scores reflected lower disease activity, with a resulting score of \<=30 on the 0-100 scale. |
| Global and US-specific Outcome Measures: Percentage of Participants With Clinical Response at Induction Week 6 as Assessed by sPCDAI | Induction Week 6 | sPCDAI clinical response was defined as reduction from baseline in the sPCDAI score of \>=10. The 6-item sPCDAI score ranges from 0 (no disease activity) to 90 (severe disease activity),calculated by summing weighted scores for abdominal pain, stool frequency, general well-being, body weight, abdominal exam, and extraintestinal manifestations. Each component was assigned a score of 0, 5, 10, or 20, depending on the severity of findings, with higher scores indicating greater disease activity, while lower scores (closer to 0) reflected minimal disease activity. Individual component scores were summed to derive the total sPCDAI score, which ranged from 0 to 90. Higher score indicate greater severity. The sPCDAI score was only calculated when \>=3 of the 6 components were available. |
| Global Outcome Measure: Percentage of Participants With Endoscopic Response at Maintenance Week 8 as Assessed by Simplified Endoscopic Score-Crohn's Disease (SES-CD) | Maintenance Period Week 8 (Study Week 16) | Endoscopic response was assessed using the Simplified Endoscopic Activity Score for Crohn's Disease (SES-CD), a validated endoscopic scoring system based on four components: size of ulcers, extent of ulcerated surface, extent of affected surface, and presence of narrowing. Each component was scored from 0 to 3 across five intestinal sections: ileum, right colon, transverse colon, left (descending and sigmoid) colon, and rectum. Component scores were summed across all sections to derive a total SES-CD score ranging from 0 to 56, with higher scores indicating greater endoscopic disease severity. Endoscopic response was defined as a \>=50% reduction from baseline in SES-CD score or achievement of an SES-CD score \<=2 in participants with a baseline SES-CD score \>=3. |
| Global Outcome Measure: Percentage of Participants With Clinical Response at Maintenance Week 8 | Maintenance Week 8 (Study Week 16) | Clinical response was defined as a reduction from baseline of \>=12.5 points in PCDAI score, calculated by summing weighted scores from 11 items across five domains: symptom history(abdominal pain, stool frequency, and general well-being); laboratory scores (hematocrit, erythrocyte sedimentation rate, and albumin); growth scores(weight and height); physical examination scores(abdominal and perirectal disease); extraintestinal manifestations. Each index item was assigned a severity score of 0(normal), 5(mild abnormality), or 10(severe abnormality). For HCT and ESR, maximum score was 5, for albumin level, maximum score was 10. Total PCDAI score ranged from 0 to 100, with higher scores indicating greater disease activity. Lower PCDAI scores reflected lower disease activity, with resulting score of \<=30 on 0-100 scale. |
| Global and US-specific Outcome Measures: Percentage of Participants With Endoscopic Response at Maintenance Week 44 as Assessed by SES-CD | Maintenance Week 44 (Study Week 52) | Endoscopic response was assessed using the Simplified Endoscopic Activity Score for Crohn's Disease (SES-CD), a validated endoscopic scoring system based on four components: size of ulcers, extent of ulcerated surface, extent of affected surface, and presence of narrowing. Each component was scored from 0 to 3 across five intestinal sections: ileum, right colon, transverse colon, left (descending and sigmoid) colon, and rectum. Component scores were summed across all sections to derive a total SES-CD score ranging from 0 to 56, with higher scores indicating greater endoscopic disease severity. Endoscopic response was defined as a \>=50% reduction from baseline in SES-CD score or achievement of an SES-CD score \<=2 in participants with a baseline SES-CD score \>=3. |
| US-specific Outcome Measure: Percentage of Participants With Clinical Response at Maintenance Week 44 | Maintenance Week 44 (Study Week 52) | Clinical response was defined as a reduction from baseline of \>=12.5 points in PCDAI score, calculated by summing weighted scores from 11 items across five domains: symptom history(abdominal pain, stool frequency, and general well-being); laboratory scores (hematocrit, erythrocyte sedimentation rate, and albumin); growth scores(weight and height); physical examination scores(abdominal and perirectal disease); extraintestinal manifestations. Each index item was assigned a severity score of 0(normal), 5(mild abnormality), or 10(severe abnormality). For HCT and ESR, maximum score was 5, for albumin level, maximum score was 10. Total PCDAI score ranged from 0 to 100, with higher scores indicating greater disease activity. Lower PCDAI scores reflected lower disease activity, with resulting score of \<=30 on 0-100 scale. |
| US-specific Outcome Measure: Percentage of Participants With Corticosteroid-free Clinical Remission at Maintenance Week 44 | Maintenance Period Week 44 (Study Week 52) | Corticosteroid-free remission was defined as PCDAI score of \<=10 points and not receiving corticosteroids for at least 90 days prior to Week M-44. The 11-item PCDAI covered five general disease activity domains: symptom history scores (3 items: abdominal pain, stool frequency; and general well-being); laboratory scores (3 items: HCT, ESR, Albumin); growth scores (2 items: weight and height), physical examination scores (2 items: abdomen and perirectal disease), and extraintestinal manifestations. The category of severity for each index item was assigned a score: 0=normal;5=mild abnormality; 10= severe abnormality. For hematocrit and erythrocyte SR, the maximum score= 5. For albumin level, the maximum score= 10. All items were summed to derive the total score. The total PCDAI score ranged from 0 to 100, with higher scores indicating greater disease activity. |
| Global Outcome Measure: Percentage of Participants With Clinical Remission at Maintenance Week 44 Who Had Clinical Remission at Induction Week 8 | Maintenance Week 44 (Study Week 52) | Clinical remission was defined as Pediatric Crohn's Disease Activity Index (PCDAI) score \<=10. The 11-item PCDAI covered five general disease activity domains: symptom history scores (3 items: abdominal pain, stool frequency; and general well-being); laboratory scores (3 items: HCT, ESR, Albumin); growth scores (2 items: weight and height), physical examination scores (2 items: abdomen and perirectal disease), and extraintestinal manifestations. The category of severity for each index item was assigned a score: 0=normal;5=mild abnormality; 10= severe abnormality. For hematocrit and erythrocyte SR, the maximum score= 5. For albumin level, the maximum score= 10. All items were summed to derive the total score. The total PCDAI score ranged from 0 to 100, with higher scores indicating greater disease activity. |
Countries
Belgium, Germany, Hungary, Israel, Japan, Poland, Russia, United Kingdom, United States
Contacts
STUDY_DIRECTORJanssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 13.5 Years STANDARD_DEVIATION 2.73 |
| Participants with a History of Biological Failure | 57 Participants |
| Pediatric Crohn's Disease Activity Index (PCDAI) Score | 41.16 Score on scale STANDARD_DEVIATION 7.62 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 9 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 88 Participants |
| Sex: Female, Male Female | 41 Participants |
| Sex: Female, Male Male | 60 Participants |
| Weight <40 kg | 29 Participants |
| Weight >=40 kg | 72 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 101 | 0 / 48 | 0 / 49 |
| other Total, other adverse events | 54 / 101 | 39 / 48 | 42 / 49 |
| serious Total, serious adverse events | 3 / 101 | 7 / 48 | 6 / 49 |
Outcome results
None listed