A Study to Assess the Efficacy and Safety of Golimumab in Pediatric Participants With Moderately to Severely Active Ulcerative Colitis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate efficacy of golimumab in inducing clinical remission as assessed by the Mayo score, in pediatric participants with moderately to severely active ulcerative colitis (UC). In addition, the safety profile of golimumab, in pediatric participants with moderately to severely active UC will be assessed.

Official Title
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A Phase 3 Randomized, Open-Label Study to Assess the Efficacy, Safety, and Pharmacokinetics of Golimumab Treatment, a Human Anti-TNFα Monoclonal Antibody, Administered Subcutaneously in Pediatric Participants With Moderately to Severely Active Ulcerative Colitis

Conditions
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Colitis, Ulcerative

Intervention / Treatment
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* Drug: Golimumab
* Drug: Infliximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must either be currently receiving treatment with, or have a history of having failed to respond to, or have a medical contraindication to at least 1 of the following therapies: oral or intravenous corticosteroids, 6-mercaptopurine, methotrexate or azathioprine OR must either have or have had a history of corticosteroid dependency (that is an inability to successfully taper corticosteroids without a return of the symptoms of ulcerative colitis [UC]) OR required more than 3 courses of corticosteroids in the past year Moderately to severely active UC (as defined by baseline Mayo score of 6 through 12 [endoscopy {sigmoidoscopy or colonoscopy} sub score assigned by local endoscopist], inclusive), including a (sigmoidoscopy or colonoscopy) sub score greater than or equal to (>=2) If receiving enteral nutrition, must have been on a stable regimen for at least 2 weeks prior to the first administration of study intervention at Week 0. Participants who receive parenteral nutrition are not permitted to enroll in the trial No history of latent or active tuberculosis prior to screening Must be up to date with all immunizations (that is, measles, mumps, rubella, and varicella) in agreement with current local immunization guidelines for immunosuppressed participants before Week 0 Exclusion Criteria: History of liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric (including suicidality), or metabolic disturbances History of malignancy or macrophage activation syndrome or hemophagocytic lymphohistiocytosis Have UC limited to the rectum only or to <20 percent (%) of the colon Presence of a stoma Presence or history of a fistula Contraindications to the use of golimumab or infliximab or anti-tumor necrosis factor (TNF-alpha) therapy per local prescribing information

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: Golimumab<br>Participants will receive subcutaneous (SC) golimumab through Week 50. Doses will be based on body surface area. Following the Week 54 evaluations (end of main pivotal study) participants who are benefiting from golimumab at the discretion of the investigator may continue to receive SC golimumab in an extension period until end of study. | Drug: Golimumab<br>* Participants receive subcutaneous (SC) golimumab through Week 50, where doses will be based on body surface area. After the Week 54 evaluations, at the discretion of investigator, participants benefiting from continued SC golimumab will continue to receive SC golimumab in the extension until end of study.<br>|
| Experimental: Group 2: Infliximab<br>Participants will receive infliximab intravenous (IV) through Week 46. Doses will be based on body weight. After the Week 54 evaluations, participants receiving infliximab will be withdrawn from study participation and transition to local standard of care which may include continued commercially available infliximab at the discretion of their physician. | Drug: Infliximab<br>* Participants will receive infliximab intravenous (IV) through Week 46. Doses will be based on body weight. After the Week 54 evaluations, participants receiving infliximab will be withdrawn from study participation and transition to local standard of care which may include continued commercially available infliximab at the discretion of their physician.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Remission at Week 6 as Assessed by the Mayo Score | Clinical remission is defined as a Mayo score less than or equal to (<=) 2 points, with no individual sub score greater than (>) 1. The Mayo score consists of 4 sub scores (stool frequency, rectal bleeding, endoscopy findings, and physician's global assessment), each of which is rated on a scale from 0 to 3, indicating normal to severe activity. The total score is calculated as the sum of the 4 sub scores and values range from 0 to 12. A score of 3 to 5 points indicates mildly active disease; a score of 6 to 10 indicates moderately active disease; and a score of 11 to 12 indicates severe disease. | At Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symptomatic Remission at Week 54 | Symptomatic remission is defined as Mayo stool frequency subscore of 0 or 1 and a rectal bleeding subscore of 0. | At Week 54 | 
| Clinical Remission at Week 54 as Assessed by the Mayo score | Clinical remission is defined as a Mayo score <=2 points, with no individual subscore >1 (based on Mayo endoscopy subscore assigned by the local endoscopist). The Mayo score consists of 4 sub scores (stool frequency, rectal bleeding, endoscopy findings, and physician's global assessment), each of which is rated on a scale from 0 to 3, indicating normal to severe activity. The total score is calculated as the sum of the 4 sub scores and values range from 0 to 12. A score of 3 to 5 points indicates mildly active disease; a score of 6 to 10 indicates moderately active disease; and a score of 11 to 12 indicates severe disease. | At Week 54 | 
| Clinical Remission at Week 54 as Assessed by the Pediatric Ulcerative Colitis Activity Index Score (PUCAI) Score | Clinical remission is defined as a PUCAI score less than (<)10. The PUCAI is a noninvasive measure of UC disease activity. It comprises 6 scales and total score ranges between 0 and 85 points. The scales are: abdominal pain, rectal bleeding, stool consistency, number of stools, nocturnal bowel movement, and activity level. The PUCAI total score is calculated as the sum of the 6 subscores. Higher scores indicate a more severe disease. | At Week 54 | 
| Clinical Remission at Week 6 as Assessed by the PUCAI Score | Clinical remission is defined as a PUCAI score <10. The PUCAI is a noninvasive measure of ulcerative colitis (UC) disease activity. It comprises 6 scales and total score ranges between 0 and 85 points. The scales are: abdominal pain, rectal bleeding, stool consistency, number of stools, nocturnal bowel movement, and activity level. The PUCAI total score is calculated as the sum of the 6 subscores. Higher scores indicate a more severe disease. | At Week 6 | 
| Clinical Response at Week 6 as Assessed by the Mayo Score | Clinical response is defined as a decrease from baseline in the Mayo score of greater than or equal to (>=)30 percent (%) and >=3 points, with either a decrease from baseline in the rectal bleeding subscore of >=1 or a rectal bleeding subscore of 0 or 1. The Mayo score consists of 4 sub scores (stool frequency, rectal bleeding, endoscopy findings, and physician's global assessment), each of which is rated on a scale from 0 to 3, indicating normal to severe activity. The total score is calculated as the sum of the 4 sub scores and values range from 0 to 12. A score of 3 to 5 points indicates mildly active disease; a score of 6 to 10 indicates moderately active disease; and a score of 11 to 12 indicates severe disease. | At Week 6 | 
| Endoscopic Healing at Week 6 | Endoscopic healing is defined as an endoscopy subscore of the Mayo score of 0 (normal or inactive disease) or 1 (mild disease). | At Week 6 | 
| Endoscopic Healing at Week 54 | Endoscopic healing is defined as an endoscopy subscore of the Mayo score of 0 (normal or active disease) or 1 (mild disease). | At Week 54 | 
| Clinical Remission at Week 54 Assessed by the Mayo score for Participants who are in Clinical Remission at Week 6 | Clinical remission is defined as a Mayo score <=2 points, with no individual subscore >1 (based on Mayo endoscopy subscore assigned by the local endoscopist). The Mayo score consists of 4 sub scores (stool frequency, rectal bleeding, endoscopy findings, and physician's global assessment), each of which is rated on a scale from 0 to 3, indicating normal to severe activity. The total score is calculated as the sum of the 4 sub scores and values range from 0 to 12. A score of 3 to 5 points indicates mildly active disease; a score of 6 to 10 indicates moderately active disease; and a score of 11 to 12 indicates severe disease. | At Week 54 | 
| Number of Participants who were not Receiving Corticosteroids for At least 12 Weeks Prior to Week 54 and in Clinical Remission at Week 54 | Number of participants who were not receiving corticosteroids for at least 12 Weeks prior to Week 54 and in clinical remission at Week 54 will be reported. | At Week 54 |