Trial Outcomes & Findings for A Study of Ustekinumab in Pediatric Participants With Moderately to Severely Active Crohn's Disease (NCT NCT04673357)

A Study of Ustekinumab in Pediatric Participants With Moderately to Severely Active Crohn's Disease

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.

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.

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.

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.

Number of participants with AEs leading to discontinuation of study intervention 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. AESI were defined as any newly identified malignancy, or case of active TB, or opportunistic infection occurring after the first administration of study intervention.

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.

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.

Number of participants with reactions temporally associated with intravenous (IV) infusion (Induction Period) and subcutaneous (SC) Injection-Site Reactions (Maintenance Period) were reported.

Serum ustekinumab concentrations were reported.

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.

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.

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.

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.

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.

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.

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.

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.

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.