E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Inflammatory bowel disease (IBD) |
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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 |
Induction study:
-To evaluate the efficacy of IV ustekinumab in inducing clinical remission in subjects with moderately to severely active ulcerative colitis (UC).
-To evaluate the safety of IV ustekinumab in subjects with moderately to severely active UC.
Maintenance study:
- To evaluate clinical remission for SC maintenance regimens of ustekinumab in subjects with moderately to severely active UC induced into clinical response with ustekinumab.
- To evaluate the safety of SC maintenance regimens of ustekinumab in subjects with moderately to severely active UC induced into clinical response with ustekinumab. |
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E.2.2 | Secondary objectives of the trial |
Induction
efficacy of IV ustekinumab in inducing endoscopic healing
efficacy of IV ustekinumab in inducing clinical response
impact of IV ustekinumab on disease-specific health-related quality of life
efficacy of ustekinumab treatment on mucosal healing
efficacy of induction therapy with IV ustekinumab by biologic failure status
PK, immunogenicity, and PD of ustekinumab induction therapy
Maintenance
efficacy in maintaining clinical response in subjects induced into clinical response with ustekinumab
endoscopic healing in subjects induced into clinical response
efficacy of ustekinumab in achieving corticosteroid-free clinical remission
efficacy of ustekinumab in maintaining clinical remission
efficacy of ustekinumab treatment on mucosal healing
impact of SC ustekinumab on disease-specific health-related quality of life
efficacy of maintenance therapy with SC ustekinumab by biologic failure status
PK, immunogenicity, and PD of ustekinumab maintenance therapy
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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 |
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E.3 | Principal inclusion criteria |
- Has a clinical diagnosis of Ulcerative Colitis (UC) at least 3 months before Screening
- Has moderately to severely active UC, defined as a Baseline (Week 0) Mayo score of 6 to 12, including a Screening endoscopy subscore of the Mayo score greater than or equal to (>=) 2 as determined by a central reading of the video endoscopy
- Have failed biologic therapy, that is, have received treatment with 1 or more tumour necrosis factor (TNF) antagonists or vedolizumab at a dose approved for the treatment of UC, and have a documented history of failure to respond to or tolerate such treatment; OR Be naïve to biologic therapy (TNF antagonists or vedolizumab) or have received biologic therapy but have not demonstrated a history of failure to respond to, or tolerate, a biologic therapy and have a prior or current UC medication history that includes at least 1 of the following:
a. Inadequate response to or failure to tolerate current treatment with oral corticosteroids or immunomodulators (6 mercaptopurine [6-MP] or azathioprine [AZA]) OR
b. History of failure to respond to, or tolerate, at least 1 of the following therapies: oral or IV corticosteroids or immunomodulators (6-MP or AZA) OR
c. History of corticosteroid dependence (that is, an inability to successfully taper corticosteroids without a return of the symptoms of UC)
- Before the first administration of study agent, the following conditions must be met: vedolizumab must have been discontinued for at least 4 months and antitumor necrosis factors (TNFs) [or approved biosimilars for these therapies] for at least 8 weeks |
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E.4 | Principal exclusion criteria |
- Has severe extensive colitis and is at imminent risk of colectomy
- Has UC limited to the rectum only or to < 20 centimeters (cm) of the colon
- Presence of a stoma or history of a fistula
- Participants with history of extensive colonic resection (for example, less than 30 cm of colon remaining) that would prevent adequate evaluation of the effect of study agent on clinical disease activity
- Participants with history of colonic mucosal dysplasia
- Participants will not be excluded from the study because of a pathology finding of “indefinite dysplasia with reactive atypia'' |
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E.5 End points |
E.5.1 | Primary end point(s) |
Induction study:
- Number of Participants With Clinical Remission
Maintenance study:
- Number of Participants with Clinical Remission Among Participants in Clinical Response to IV Ustekinumab Induction Treatment |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Induction study:
- Week 8
Maintenance study:
- Week 44 |
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E.5.2 | Secondary end point(s) |
Induction study:
1) Number of Participants with Clinical Response
2) Number of Participants With Endoscopic Healing
3) Mean Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Score
Maintenance study:
1) Participants with Clinical Response Among Participants in Clinical Response to IV Ustekinumab Induction Treatment
2) Number of Participants with Endoscopic Healing Among Participants in Clinical Response to IV Ustekinumab Induction Treatment
3) Number of Participants with Clinical Remission and not receiving concomitant corticosteroids at Week 44
4) Number of Participants with Clinical Remission Among those who Achieved Clinical Remission at Maintenance Study Baseline
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Induction study:
1-3) Week 8
Maintenance study:
1-4) Week 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 | Yes |
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 | Yes |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 10 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 139 |
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 |
Australia |
Canada |
Israel |
Korea, Republic of |
New Zealand |
Russian Federation |
Serbia |
South Africa |
United States |
Austria |
Belgium |
Bulgaria |
Czechia |
Denmark |
France |
Germany |
Hungary |
Italy |
Netherlands |
Poland |
Romania |
Slovakia |
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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The study is considered completed with the last visit for the last subject participating in the LTE. |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 5 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |