Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT05092269 | A Long-term Extension Study of Ustekinumab in Pediatric Participants | PHASE3 | ACTIVE NOT_RECRUITING | 159 | — | — | Oct 18, 2021 | Mar 15, 2028 | Jun 5, 2026 | 48 | United States, Argentina +11 |
| NCT04673357 | A Study of Ustekinumab in Pediatric Participants With Moderately to Severely Active Crohn's Disease | PHASE3 | COMPLETED | 101 | — | — | Apr 6, 2021 | Mar 3, 2025 | Nov 28, 2025 | 53 | United States, Belgium +7 |
| NCT03464136 | Safety and Efficacy of Adalimumab Versus Ustekinumab for One Year | PHASE3 | COMPLETED | 386 | — | — | Mar 29, 2018 | May 21, 2021 | Apr 29, 2025 | 182 | United States, Australia +16 |
| NCT03107793 | Study of Treat to Target Versus Routine Care Maintenance Strategies in Crohn's Disease Patients Treated With Ustekinumab | PHASE3 | COMPLETED | 500 | — | — | Apr 19, 2017 | Jul 20, 2021 | Apr 29, 2025 | 107 | Belgium, Czechia +10 |
| NCT02968108 | A Pharmacokinetic Study of Ustekinumab in Pediatric Subjects With Moderately to Severely Active Crohn's Disease | PHASE1 | COMPLETED | 45 | — | — | Jan 18, 2017 | Mar 18, 2022 | Apr 27, 2025 | 26 | United States, Belgium +4 |
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.
A SAE is 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; congenital anomaly.
Number of participants with AEs leading to discontinuation of study intervention will be reported.
Number of participants with AEs of special interest (any newly identified malignancy 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 (such as hematology and serum chemistry) will be reported.
Number of participants with injection-site reactions will be reported. An injection-site reaction is any adverse reaction at a subcutaneous (SC) study intervention injection-site.
Number of participants with AEs of worsening of the disease will be reported.
Number of participants with concomitant therapy due to loss of response will be reported.
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 reactions temporally associated with IV infusion in induction period will be reported.
Number of participants with SC injection-site reactions in maintenance period will be reported.
Serum ustekinumab concentrations will be reported.
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.
Percentage of participants with clinical remission at Week 52 were assessed. Clinical remission was defined as a Crohn's Disease Activity Index (CDAI) score of less than (\<) 150 points (in general, CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities). The CDAI score is used to quantify the symptoms of participants with Crohn's Disease. A decrease in CDAI over time indicates improvement in disease activity.
Endoscopic response defined as showing a reduction from baseline in simple endoscopic score for Crohn's disease (SES-CD) of greater than or equal to (\>=) 50 percent (%). SES-CD is a validated instrument reflecting an endoscopist global appraisal of mucosal lesions in Crohn's disease. SES-CD grades lesions by location (5 bowel segments: ileum, right colon, transverse colon, left colon, and rectum) using 4 endoscopic variables: ulcer size, extent of ulcerated surface, extent of affected surface, and presence/type of narrowing. Total SES-CD is sum of 4 variables for all 5 bowel segments. Scores range from 0-60 with higher scores indicating more severe disease. Randomized participants who stopped treatment before reaching Week 48 due to any reason, or participants without endoscopic data at Week 48 were analyzed as nonresponders.
Serum samples will be collected to measure seum concentrations of Ustekinumab.
| Arm | Type | Description |
|---|---|---|
| Ustekinumab | EXPERIMENTAL | Participants will have continued access to ustekinumab for primary study (CNTO1275CRD1001, CNTO1275PUC3001, CNTO1275CRD3004, CNTO1275JPA3001) participants who in the opinion of the investigator will continue to benefit from ustekinumab therapy. All blinded participants who enroll in the long-term extension (LTE) from blinded primary studies with both every 8 weeks (q8w) and every 12 weeks (q12w) dosing groups just prior to the end of the primary study will be assigned to the q8w dosing regimen. Participants enrolling in the LTE from an unblinded primary study will remain on the final dosing regimen that they were receiving in the primary study. Participants enrolling from the Exposure Optimization Substudy may be eligible to remain on the every 4 weeks (q4w) dosing regimen. |
| Open- Label Ustekinumab Intravenous (IV): Induction Period | EXPERIMENTAL | 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 | EXPERIMENTAL | 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 | EXPERIMENTAL | 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. |
| Group 1 (Ustekinumab) | EXPERIMENTAL | Participants will receive intravenous (IV) infusion of ustekinumab (approximately 6 milligram/kilogram \[mg/kg\]) and 4 subcutaneous (SC) injections of placebo for adalimumab at Week 0, followed by 2 SC injections of placebo at Week 2. From Week 4 to Week 56, participants will self-administer one SC injection of ustekinumab 90 milligram (mg) every 8 weeks (q8w) starting at Week 8 and placebo adalimumab at the other designated every 2 weeks (q2w) dosing intervals. |
| Group 2 (Adalimumab) | ACTIVE_COMPARATOR | Participants will receive IV infusion of placebo for ustekinumab and 4 SC injections of adalimumab (each 40 mg, total dose 160 mg) at Week 0, followed by 2 SC injections of adalimumab (each 40 mg, total dose 80 mg) at Week 2. From Week 4 to Week 56, participants will self-administer 1 SC injection of adalimumab 40 mg q2w. |
| All Participants | EXPERIMENTAL | At Week (Wk) 0, all eligible participants will initiate intravenous (IV) induction treatment with ustekinumab (UST) on a weight-tiered basis at a dose of approximately 6 milligram per kilogram (mg/kg). At Week 8, all participants will receive a 90 milligram (mg) subcutaneous (SC) injection of ustekinumab. At Week 16, participants who do not achieve a Crohn's Disease Activity Index (CDAI) improvement of greater than or equal to (\>=) 70 points versus Week 0 (CDAI 70) will leave the study. Remaining participants will be randomized in a 1:1 ratio to either one of two arms for open label maintenance treatment up to Week 48: the treat to target arm or the routine care arm. From Week 48, participants will continue ustekinumab treatment in the study extension period, up to Week 104. Dosing frequency will be adjusted in the extension period for the participants failing to meet the treatment target. |
| Routine Care Arm | EXPERIMENTAL | In the routine care arm, assessment visits will be scheduled according to the timing of maintenance treatment injections up to Week 48, which will be in compliance with the EU SmPC for ustekinumab for the treatment of Crohn's disease, in which dosing every 12 weeks is recommended. At Week 16, (that is, 8 weeks after the first SC dose) participants continuing in the study will have demonstrated a CDAI-70 response. Nonetheless, participants who have not shown adequate response based on the investigator's judgment may receive a second SC dose at Week 16. During the routine care maintenance treatment period, in case of clinical worsening reported by the participant, consistent with disease flare in the investigator's judgment, clinical assessments of disease flare will be performed at the investigator's discretion. |
| Treat to Target (T2T) Arm | EXPERIMENTAL | UST maintenance treatment assignment will be based on centrally-read colonoscopy (at Wk16). Participants with \<25% improvement in SES-CD score at Wk16 will be assigned to Q8 (8-weekly) treatment and will receive UST 90mg SC at Wk16. In contrast, participants with \>=25% improvement in SES-CD score at Wk16 will be assigned to Q12 treatment and will receive next UST dose (90 mg SC) at Wk20. At assessment visits (from Wk24 for participants assigned to the Q8 regimen or from Wk20 for the Q12 group) UST maintenance treatment (up to Wk 48) will be directed by T2T assessments. Participants meeting target will continue with same UST dosing frequency. The dosing frequency will be optimized for all participants failing to meet the target at assessment visit. Those previously on Q12 regimens will be adjusted to Q8 dosing; those previously on Q8 regimens will be adjusted to Q4 dosing. Participants subsequently failing to meet the target will not be able to adjust further and will leave the study. |
| Exploratory Extension period: From Week 48 to Week 104 | EXPERIMENTAL | At Week 48, dose de-escalation will be implemented for participants with both endoscopic remission (SES-CD score \<=2) and corticosteroid-free clinical remission of at least 16 weeks duration. Participants receiving 12 weekly dosing frequency (Q12) ustekinumab will maintain this dosing frequency. Participants with either clinical remission or endoscopic remission, but not both, at Week 48 will continue with same dosing frequency or de-escalate provided maintenance of corticosteroid-free clinical remission and biomarker remission at 2 consecutive visits. Participants with neither corticosteroid-free clinical remission nor endoscopic remission will escalate dose or leave study if already on 4 weekly dosing frequency (Q4) dose. If neither clinical remission nor biomarker remission is evident at the next visit, participant will leave study. Later in the extension period, only those who achieve corticosteroid-free clinical remission and biomarker remission will undergo dose de-escalation. |
| Group1: Ustekinumab Dose Regimen 1 | EXPERIMENTAL | Subjects will receive a single intravenous (IV) induction dose of 3 milligram per kilogram (mg/kg) for subjects less than \< 40 kilogram (kg) or 130 milligram (mg) for subjects greater than or equal to \>= 40 kg at Week 0 followed by subcutaneous (SC) maintenance dose of 2 mg/kg for subjects \< 40 kg or 90 mg for subjects \>= 40 kg at week 8. |
| Group2: Ustekinumab Dose Regimen 2 | EXPERIMENTAL | Subjects will receive a single Intravenous (IV) dose of 9 mg/kg for subjects \<40 kg or 390 mg for subjects \>= 40 kg at Week 0 followed by SC maintenance dose of 2 mg/kg for subjects \<40 kg or 90 mg for subjects \>= 40 kg at week 8. |
| Name | Type | Description |
|---|---|---|
| Ustekinumab | DRUG | Ustekinumab will be administered as a SC injection. |
| Placebo | DRUG | Matching placebo will be administered as SC injection. |
| Placebo for Ustekinumab | BIOLOGICAL | Participants will receive placebo as SC injection to blind adalimumab. |
| Placebo for Adalimumab | BIOLOGICAL | Participants will receive placebo as IV infusion to blind ustekinumab. |
| Ustekinumab (6 mg/kg) | BIOLOGICAL | Participants will receive ustekinumab 6 mg/kg (weight based dosing) as IV infusion. |
| Ustekinumab (90 mg) | BIOLOGICAL | Participants will self-administer SC injection of ustekinumab 90 mg. |
| Adalimumab (40 mg) | BIOLOGICAL | Participants will self-administer multiple SC injections of adalimumab (each 40 mg) and will receive total dose of 160 mg at Week 0, 80 mg at Week 2, and 40 mg q2w from Week 4 to 56. |
Inclusion Criteria: * Must have completed the dosing planned in the primary pediatric ustekinumab study * Benefit of continued ustekinumab therapy (that is, a clinical response or clinical remission as defined in the primary study at the final efficacy visit of the primary study) * Parent(s) (prefe...