| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Ulcerative Colitis or Crohn’s Disease |
|
| E.1.1.1 | Medical condition in easily understood language |
Ulcerative colitis is an inflammatory disease of the large bowel.
Crohn's disease is an inflammatory disease of the gastrointestinal tract. |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
| 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.1.2 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 | 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 |
- To determine the safety profile of long-term vedolizumab IV treatment in pediatric subjects with UC or CD.
|
|
| E.2.2 | Secondary objectives of the trial |
- To evaluate the efficacy of long-term vedolizumab IV in pediatric
subjects with UC or CD.
-To determine the effect of long-term vedolizumab IV treatment on time to major inflammatory bowel disease (IBD)-related events (hospitalizations, surgeries, and procedures) in pediatric subjects with UC or CD.
-To examine the effect of long-term vedolizumab IV treatment on health-related quality-of- life measurements in pediatric subjects with UC or CD.
-To determine the effect of long-term vedolizumab IV treatment on patterns of growth and development in pediatric subjects with UC or CD. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
-The subject is male or female with UC or CD and was between 2 to 17 years, inclusive, at the time of their randomization in Study MLN0002-2003. (Note: A subject remains eligible to participate in this study after they reach 18 years of age if they continue to meet the inclusion criteria and do not meet any exclusion criteria.)
-The subject completed Study MLN0002-2003 and, at Week 22, achieved clinical response as defined by a reduction of partial Mayo score of ≥2 points and ≥25% from Baseline, or a reduction of the PUCAI of ≥20 points from baseline for subjects with UC; or a reduction of the CDAI as defined by a ≥70-point decrease from Baseline or a decrease of PCDAI of ≥15 points for subjects with CD.
-Subjects with a family history of colorectal cancer, personal history of increased colorectal cancer risk, or other known risk factor must be up-to-date on colorectal cancer surveillance.
-The subject may be receiving a therapeutic dose of the following drugs:
– Oral 5-aminosalicylic (5-ASA) compounds.
– Oral corticosteroid therapy (prednisone or equivalent steroid at a dose ≤50 mg/day).
– Topical (rectal) treatment with 5-ASA or corticosteroids.
– Probiotics (eg, Saccharomyces boulardii).
– Antidiarrheals (eg, loperamide, diphenoxylate with atropine) for control of chronic diarrhea.
– Antibiotics used for treatment of CD (eg, ciprofloxacin, metronidazole).
– Azathioprine, 6-mercaptopurine, or methotrexate provided the subject was receiving this medication during prior participation in Study MLN0002-2003. |
|
| E.4 | Principal exclusion criteria |
-The subject is female and is lactating or pregnant.
-The subject has hypersensitivity or allergies to vedolizumab or any of its excipients.
-The subject has withdrawn from Study MLN0002-2003.
-The subject has developed any new unstable or uncontrolled cardiovascular, heart failure moderate to severe (New York Class Association III or IV), pulmonary, hepatic, renal, gastrointestinal, genitourinary, hematological, coagulation, immunological, endocrine/metabolic, neurological, or other medical disorder that, in the opinion of the investigator, would confound the study results or compromise subject safety.
-The subject has a positive progressive multifocal leukoencephalopathy (PML) subjective symptom checklist prior to the administration of the first dose of study drug.
-The subject currently requires major surgical intervention for UC or CD (eg, bowel resection), or is anticipated to require major surgical intervention for UC or CD during the study.
-The subject has other serious comorbidities that will limit their ability to complete the study. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary endpoint for this study is percentage of subjects with treatment-emergent adverse events (TEAEs).
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Monitored throughout the study |
|
| E.5.2 | Secondary end point(s) |
The secondary endpoints for this study are:
- Percentage of UC subjects who, at Week 32, achieve and maintain clinical response based on complete Mayo score, as defined by a continued reduction in complete Mayo score of ≥3 points from the baseline (at initiation of MLN0002-2003) and continued decrease in rectal bleeding subscore of ≥1 point from baseline, or absolute rectal bleeding subscore of ≤1 point at Week 32.
- Percentage of CD subjects who, at Week 32, achieve and maintain clinical response as defined by a 50% reduction in SES-CD score on endoscopy compared to the baseline endoscopy (at initiation of MLN0002-2003); and continued reduction in CDAI that is a ≥70 point decrease from the baseline CDAI score at the initiation of MLN0002- 2003.
- Time to major IBD-related events (hospitalizations, surgeries, or procedures).
- Changes from Baseline in IMPACT-III (where translations are available) total and subscale scores at Week 24 and every 24 weeks, thereafter.
- Height velocity at Week 48 and every 48 weeks, thereafter.
- Change from Baseline in height, weight, and body mass index (BMI) at Week 24 and every 24 weeks, thereafter.
- Percentage of subjects achieving Tanner stage V at or before age 16 years (females) or 17 years (males). |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Monitored throughout the study |
|
| 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 | No |
| E.6.7 | Pharmacodynamic | No |
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | No |
| 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 | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| At week 40 the blinding will be lifted. |
|
| 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 | Yes |
| E.8.2.3.1 | Comparator description |
| Vedolizumab to be tested at doses of 300mg, 200mg, 150 mg and 100mg |
|
| 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 | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 28 |
| 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 |
| Belgium |
| Canada |
| France |
| Germany |
| Hungary |
| Israel |
| Netherlands |
| Poland |
| Ukraine |
| United Kingdom |
| United States |
|
| 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
|
| Final Safety Visit 18 weeks after last dose of study drug and participate in a long-term follow-up safety survey by telephone 6 months after the last dose of study drug. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 7 |
| E.8.9.1 | In the Member State concerned months | 7 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 7 |
| E.8.9.2 | In all countries concerned by the trial months | 7 |
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