E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Ulcerative Colitis in pediatric subjects |
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E.1.1.1 | Medical condition in easily understood language |
Ulcerative Colitis in pediatric subjects |
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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 | 14.1 |
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 |
To evaluate the PK of golimumab in pediatric subjects aged 2 through 17 years with moderately to severely active UC.
To evaluate the safety of golimumab in pediatric subjects aged 2 through 17 years with moderately to severely active UC.
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of golimumab induction (ie, short-term therapy) in pediatric subjects aged 2 through 17 years with moderately to severely active UC. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Children aged 2 to 17 years of either gender.
• Have moderately to severely active ulcerative colitis (UC), defined as a baseline Mayo score of 6 to 12, inclusive.
• Had UC diagnosed, or was referred to the investigator to establish a diagnosis of UC, at least 2 weeks prior to screening.
• Have the diagnosis of UC confirmed by a previous biopsy (tissue or cell sample) or results from a biopsy conducted at the screening endoscopy procedure that is consistent with a diagnosis of UC.
• Have a Mayo endoscopy subscore ≥ 2 at screening sigmoidoscopy (procedure to examine the large intestine) [indicative of moderately to severely active UC]. A sigmoidoscopy performed within 2 weeks prior to baseline but before informed consent is obtained may be considered the screening sigmoidoscopy if performed by an investigator at the site.
• Prior or current medication for UC must include at least 1 of the following: a) current treatment with at least 1 of the following therapies: oral or intravenous corticosteroids, or the immunomodulators 6-MP or azathioprine (AZA); or b) have a history of failure to respond to or tolerate, or have a medical contraindication to, at least 1 of the following therapies: oral or intravenous corticosteroids or the immunomodulators 6-MP or AZA; or c) currently have or have had a history of corticosteroid dependency (ie, an inability to successfully taper corticosteroids without a return of the symptoms of UC); or d) have required more than 3 courses of oral or intravenous corticosteroids in the past year. |
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E.4 | Principal exclusion criteria |
• Have severe extensive colitis as evidenced by investigator judgment that the participant is likely to require a colectomy within 12 weeks of baseline; or symptom complex at screening or baseline visits that includes at least 4 of the following: 1) diarrhea with ≥ 6 bowel movements/day with macroscopic blood in stool; 2) focal severe or rebound abdominal tenderness; 3) persistent fever (≥ 37.5°C); 4) tachycardia (> 90 beats/minute); or 5) anemia (hemoglobin < 8.5 g/dL).
• Have UC limited to the rectum only or to < 20 cm of the colon.
• Presence of a stoma (a medical opening in the abdomen).
• Presence or history of a fistula (an abnormal passageway between two organs of the body).
• Have severe, fixed symptomatic stenosis (narrowing) of the large or small intestine. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Serum golimumab concentration at Week 6
• Area under the curve (of serum concentrations) for golimumab from Week 0 to Week 6 (AUC0-6 weeks) |
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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) |
• Number of adverse events up to Week 126
• Physical examination assessments up to Week 126
• Injection-site reactions up to Week 126
• Vital signs assessments up to Week 126
• Clinical laboratory tests up to Week 126
• Early detection of active tuberculosis up to Week 126
• Clinical response at Week 6
• Clinical remission at Week 6 as measured by the Mayo score, which includes stool frequency, rectal bleeding, endoscopy findings, and physician’s global assessment
• Pediatric Ulcerative Colitis Activity Index (PUCAI) remission up to Week 110. The PUCAI score includes abdominal pain, rectal bleeding, stool consistency, number of stools, nocturnal bowel movement, and activity level.
• Mucosal healing at Week 6 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Open-Label Study to Assess the Safety and Pharmacokinetics |
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E.7.2 | Therapeutic exploratory (Phase II) | No |
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 | 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 | No |
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 | 1 |
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 | 15 |
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 |
Austria |
Belgium |
Canada |
Denmark |
France |
Germany |
Israel |
Netherlands |
Poland |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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 end of study is defined as the completion of the final visit for the last subject 16 weeks after his or her last administration of study agent in the study. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 14 |
E.8.9.2 | In all countries concerned by the trial years | 10 |