E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderately to Severely Active Crohn's Disease |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10011401 |
E.1.2 | Term | Crohn's disease |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Global: 1. To evaluate the efficacy of ustekinumab dosing in inducing clinical remission in pediatric participants with moderately to severely Crohn's disease 2. To evaluate the safety profile of ustekinumab in pediatric participants with moderately to severely active Crohn's disease. 3. To evaluate ustekinumab exposure (PK).
US specific: 4. To evaluate the efficacy of ustekinumab dosing in maintaining clinical remission among participants who were in clinical response in induction. 5. To evaluate the safety profile of ustekinumab. 6. To evaluate ustekinumab exposure (pharmacokinetics [PK]). |
|
E.2.2 | Secondary objectives of the trial |
1. To evaluate the efficacy of IV ustekinumab during the induction period. 2. To evaluate the efficacy of SC ustekinumab during the maintenance period among participants who were in clinical response in induction. |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
An optional Exposure Optimization Substudy, as described in Appendix 17 of the Protocol, for induction nonresponders who have a low steadystate, 8 weeks post-dose ustekinumab concentration, and for induction responders and delayed responders who lose response during maintenance and have a low steady-state, 8 weeks post-dose ustekinumab concentration.
Primary Objective: - To determine if a q4w dose regimen in participants who have induction nonresponse or LOR and low 8 week steady-state ustekinumab trough concentrations during maintenance will result in steady-state ustekinumab trough exposures ≥1.4 ug/mL - To evaluate the safety and immunogenicity of ustekinumab administered q4w in participants who have induction nonresponse or LOR and low ustekinumab exposure |
|
E.3 | Principal inclusion criteria |
Each potential participant must satisfy all of the following criteria to be enrolled in the study:
- 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 1-0 prior to study intervention administration
Please refer to protocol for all the inclusion criteria. |
|
E.4 | Principal exclusion criteria |
Any potential participant who meets any of the following criteria will be excluded from participating in the study:
- 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
Please refer to protocol for all the exclusion criteria. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Global 1. Clinical remission at Induction Week 8 (Week I-8).
US-specific 2. Clinical remission at Maintenance Week (Week M-44). |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Secondary endpoints are:
Global 1. Clinical remission at Week I-6 as assessed by sPCDAI 2. Clinical response at Week I-8 3. Clinical response at Week I-6 as assessed by sPCDAI 4. Endoscopic response at Maintenance Week 8 (Week M-8) as assessed by SES-CD 5. Clinical response at Week M-8
The following endpoints will be evaluated for participants who are clinical responders at Week I-8: 6. Clinical remission at Week M-44 7. Endoscopic response at Week M-44 as assessed by SES-CD 8. Clinical response at Week M-44 9. Corticosteriod-free clinical remission at Week M-44 10. Clinical remission at Week M-44 for participants who are in clinical remission at Week I-8
US-specific 11. Clinical Remission at Week I-8 12. Clinical Remission at Week I-6 as assessed by sPCDAI 13. Clinical Response at Week I-8 14. Clinical response at Week I-6 as assessed by sPCDAI 15. Endoscopic response at Week M-8 as assessed by SES-CD 16. Clinical response at Week M-8
The following endpoints will be evaluated for participants who are clinical responders at Week I-8: 17. Endoscopic response at Week M-44 as assessed by SES-CD 18. Clinical response at Week M-44 19. Corticosteroid-free clinical remission at Week M-44 20. Clinical remission at Week M-44 for participants who are in clinical remission at Week I-8 |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1, 3, 13 and 15 Week I-6 2, 12 and 14 Week I-8 4, 5, 16 and 17 Week M-8 6 - 11 and 18 - 22 Week M-44 |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Maintenance Period: Randomized, double-blind, parallel group 2-arm study |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 21 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Japan |
United States |
Belgium |
Germany |
Hungary |
Poland |
United Kingdom |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 17 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |