A Phase 3 Study of the Efficacy, Safety and Pharmacokinetics of Ustekinumab as Open-label Intravenous Induction Treatment Followed by Randomized Double-blind Subcutaneous Ustekinumab Maintenance in Pediatric Participants With Moderately to Severely Active Ulcerative Colitis
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Enrollment
- 112
- Locations
- 58
- Primary Endpoint
- Serum Concentration of Ustekinumab
Study Overview
Brief Summary
The purpose of this study is to evaluate: a) the efficacy of ustekinumab dosing in inducing clinical remission, b) safety profile of ustekinumab, and c) ustekinumab exposure (pharmacokinetics [PK]) in pediatric participants with moderately to severely active UC.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 2 Years to 17 Years (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Medically stable on the basis of physical examination, medical history, and vital signs, performed at screening. Any abnormalities must be consistent with the underlying illness in the study population and this determination must be recorded in the participant's source documents and acknowledged by the investigator
- •Must have had UC diagnosed prior to screening
- •Have moderately to severely active UC, defined as a baseline Mayo score of 6 through 12, inclusive, with a screening Mayo endoscopy subscore greater than or equal to (>=) 2 as determined by a central review of the video of the endoscopy
- •A participant who has had extensive colitis for >= 8 years, or disease limited to the left side of the colon for >= 10 years, must: a) have had a full colonoscopy to assess for the presence of dysplasia within 1 year before the first administration of study intervention or b) have a full colonoscopy with surveillance for dysplasia as the baseline endoscopy during the screening period. Results from these surveillance biopsies must be negative for dysplasia (low-grade, high-grade, or indeterminant) prior to the first administration of study intervention
- •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
- •Have UC limited to the rectum only or to less than (<) 20 centimeter (cm) of the colon
- •Presence or history of colonic or small bowel obstruction within 6 months prior to screening, confirmed by objective radiographic or endoscopic evidence of a stricture with resulting obstruction (dilation of the colon or small bowel proximal to the stricture on barium radiograph or an inability to traverse the stricture at endoscopy)
- •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
- •Has known allergies, hypersensitivity, or intolerance to ustekinumab or its excipients
Arms & Interventions
Maintenance (M) Period: Ustekinumab once every 8 Week (q8w)
Participants will receive subcutaneous (SC) administration of ustekinumab every 8 weeks (q8w) based on BSA (mg/m^2) or weight-tiered induction dose (mg/kg) at Weeks M-0, M-8, M-16, M-24, M-32, M-40 and matching placebo at Weeks M-12 and M-36 to maintain the blind.
Intervention: Matching Placebo (Drug)
Maintenance (M) Period: Ustekinumab once every 12 Week (q12w)
Participants will receive SC administration of ustekinumab every 12 weeks (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.
Intervention: Matching Placebo (Drug)
Maintenance (M) Period: Ustekinumab once every 12 Week (q12w)
Participants will receive SC administration of ustekinumab every 12 weeks (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.
Intervention: Ustekinumab Dose Based on BSA and Body Weight (Drug)
Induction Period (I): Ustekinumab
All participants will receive a single intravenous (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]).
Intervention: Ustekinumab Dose Based on BSA and Body Weight (Drug)
Maintenance (M) Period: Ustekinumab once every 8 Week (q8w)
Participants will receive subcutaneous (SC) administration of ustekinumab every 8 weeks (q8w) based on BSA (mg/m^2) or weight-tiered induction dose (mg/kg) at Weeks M-0, M-8, M-16, M-24, M-32, M-40 and matching placebo at Weeks M-12 and M-36 to maintain the blind.
Intervention: Ustekinumab Dose Based on BSA and Body Weight (Drug)
Outcomes
Primary Outcomes
Serum Concentration of Ustekinumab
Time Frame: Up to 74 weeks
Serum samples will be analyzed to determine concentrations of ustekinumab.
Number of Participants with Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability
Time Frame: Up to 74 weeks
SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect, and suspects transmission of any infectious agent via a medicinal product.
Number of Participants with AEs Leading to Discontinuation of Study Intervention
Time Frame: Up to 74 weeks
Number of Participants with discontinuation of study intervention due to an AE, infections, injection-site reactions, and AEs during or within 1 hour of an infusion will be reported.
Number of Participants with AEs of Special Interest (AESI) as a Measure of Safety and Tolerability
Time Frame: Up to 74 weeks
AESI of any newly identified malignancy, case of active tuberculosis (TB), or opportunistic infection occurring after the first administration of study intervention(s) in participants will be reported.
Number of Participants with Laboratory Abnormalities
Time Frame: Up to 74 weeks
Number of participants with laboratory abnormalities related to hematology, serum chemistry, and coagulation will be reported.
Reactions Temporally Associated with an Intravenous (IV) Infusion and Subcutaneous (SC) Injection-site Reactions
Time Frame: Up to 74 weeks
Reactions temporally associated with an IV infusion (induction period) and SC injection-site reactions (maintenance period) will be reported.
US Specific: Clinical Remission at M-44 for Participants who are in Clinical Response at I-8
Time Frame: Week 52
Clinical remission at M-44 for participants who are in clinical response at I-8 will be reported. Clinical remission is defined as a Mayo stool frequency subscore of 0 or 1, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability present on the endoscopy, where the stool frequency subscore has not increased from induction baseline.
Global: Number of Participants with Clinical Remission at Induction Week 8 (I-8) Visit
Time Frame: Week 8
Clinical remission is defined as Mayo stool frequency subscore of 0 or 1, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability present on the endoscopy, where the stool frequency subscore has not increased from induction baseline.
Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability
Time Frame: Up to 74 weeks
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.
Secondary Outcomes
- Endoscopic Improvement at I-8 Visit(Week 8)
- Number of Participants with Symptomatic Remission at M-44 Visit(Week 52)
- Number of Participants With Clinical Response at I-8 Visit(Week 8)
- Number of Participants with Symptomatic Remission at I-8 Visit(Week 8)
- Histologic-endoscopic Mucosal Improvement at Week I-8(Week 8)
- Clinical Remission at M-44 as Assessed by the PUCAI Score(Week 52)
- Clinical Remission at M-44 and not Receiving Corticosteroids for at Least 90 Days Prior to M-44 Among Participants who Received Corticosteroids at M-0(Week 52)
- Clinical Remission at I-8 as Assessed by the Pediatric Ulcerative Colitis Activity Index Score (PUCAI) Score(Week 8)
- Clinical Remission at M-44 for Participants who are in Clinical Remission at I-8(Week 52)
- Histologic-endoscopic Mucosal Improvement at Week M-44(Week 52)
- Number of Participants with Clinical Remission at Week 44 (M-44) Visit(Week 52)
- Endoscopic Improvement at M-44 Visit(Week 52)
- Corticosteroid-free Clinical Remission at Week M-44(Week 52)
- US Specific: Number of Participants with Clinical Remission at I-8 Visit(Week 8)