E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderately to Severely Active Ulcerative Colitis |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045365 |
E.1.2 | Term | Ulcerative colitis |
E.1.2 | System Organ Class | 100000004856 |
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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 active UC. 2. To evaluate the safety profile of ustekinumab in pediatric participants with moderately to severely active UC. 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]). |
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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. |
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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 19 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 postdose 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 μg/mL - To evaluate the safety and immunogenicity of ustekinumab administered q4w in participants who have induction nonresponse or LOR and low ustekinumab exposure |
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E.3 | Principal inclusion criteria |
Each potential participant must satisfy all of the following criteria to be enrolled in the study:
- 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 orb) 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 1-0 prior to study intervention administration
Please refer to protocol for all the inclusion criteria. |
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E.4 | Principal exclusion criteria |
Any potential participant who meets any of the following criteria will be excluded from participating in the study:
- 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
Please refer to protocol for all the exclusion criteria. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Global 1. Clinical remission at Week I-8.
US-specific 2. Clinical remission at Week M-44. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary endpoints are:
Global 1. Clinical response at Week I-8. 2. Symptomatic remission at Week I-8. 3. Clinical remission at Week I-8 as assessed by the Pediatric Ulcerative Colitis Activity Index (PUCAI) score. 4. Endoscopic improvement at Week I-8. 5. Clinical remission at Maintenance Week (Week M-44.) 6. Histologic-endoscopic mucosal improvement at Week I-8. 7. Clinical remission at Week M-44. 8. Symptomatic remission at Week M-44. 9. Clinical remission at Week M-44 as assessed by the PUCAI score. 10. Endoscopic improvement at Week M-44. 11. Corticosteroid-free clinical remission at Week M-44. 12. Clinical remission at Week M-44 and not receiving corticosteroids for at least 90 days prior to Week M-44 among participants who received corticosteroids at Week I-0. 13. Clinical remission at Week M-44 for participants who are in clinical remission at Week I-8. 14. Histologic-endoscopic mucosal improvement at Week M-44.
US-specific 15. Clinical remission at Week I-8. 16. Clinical response at Week I-8. 17. Symptomatic remission at Week I-8. 18. Clinical remission at Week I-8 as assessed by the PUCAI score. 19. Endoscopic improvement at Week I-8. 20. Histologic-endoscopic mucosal improvement at Week I-8. 21. Symptomatic remission at Week M-44. 22. Clinical remission at Week M-44 as assessed by the PUCAI score. 23. Endoscopic improvement at Week M-44. 24. Corticosteroid-free clinical remission at Week M-44. 25. Clinical remission at Week M-44 and not receiving corticosteroids for at least 90 days prior to Week M-44 among participants who received corticosteroids at Week I-0. 26. Clinical remission at Week M-44 for participants who are in clinical remission at Week I-8. 27. Histologic-endoscopic mucosal improvement at Week M-44. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1 to 4. and 11 to 15. Week I-8 5 to 10. and 16 to 20. Week M-44 |
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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 |
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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 | 22 |
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 |
Poland |
Germany |
Belgium |
Hungary |
United Kingdom |
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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
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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 |