Safety and Efficacy of MMX Mesalamine/Mesalazine in Pediatric Subjects With Mild to Moderate Ulcerative Colitis

Study Overview
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Brief Summary
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To assess clinical response to MMX mesalamine/mesalazine between a low and high dose in children and adolescents aged 5-17 years with mild to moderate Ulcerative Colitis (UC) or who are in remission.

Official Title
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A Phase 3, Multicenter, Randomized, Double-blind Study to Determine the Safety and Efficacy of MMX Mesalamine/Mesalazine in Pediatric Subjects With Mild to Moderate Ulcerative Colitis, in Both Acute and Maintenance Phases

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: MMX Mesalamine/Mesalazine (Low Dose)
* Drug: MMX Mesalamine/Mesalazine (High Dose)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to voluntarily provide written, signed, and dated (personally or via a legally authorized representative [LAR]) informed consent or assent as applicable to participate in the study. Subject's parent/LAR demonstrates an understanding, ability, and willingness to fully comply with study procedures and restrictions. Male and female children and adolescents aged 5-17 years, inclusive. Body weight 18-90kg. Male, or non-pregnant, non-lactating female who agrees to comply with any applicable contraceptive requirements of the protocol or females of non-childbearing potential. Diagnosed with mild to moderate UC, established by sigmoidoscopy or colonoscopy with compatible histology. Screened subjects may also have an unconfirmed diagnosis of mild to moderate UC; however the diagnosis of mild to moderate UC must have been established by sigmoidoscopy or colonoscopy with compatible histology prior to baseline visit. Subject is able to swallow the investigational product whole. Double-blind Acute Phase: Partial UC-DAI score ≥2 (a combined rectal bleeding and stool frequency score ≥1 and PGA=1 or 2) at the Baseline Visit, for which 5-ASA would be used as part of normal treatment. If the subject is on 5-ASA treatment prior to study entry, then the dose must be stable. Stable therapy is defined as no change in dose, or no initiation of 5-ASA, from the onset of the current acute flare through discontinuation of therapy (required at the Baseline Visit). Double-blind Maintenance Phase: Partial UC-DAI ≤1 (rectal bleeding=0, stool frequency ≤1, and PGA=0) at the Baseline Visit. Exclusion Criteria: Severe UC (defined by PGA=3). Crohn's disease, bleeding disorders, active peptic ulcer disease, or UC known to be confined to the rectum (isolated rectal proctitis). Asthma, only if known to be 5 ASA sensitive. Positive stool culture for enteric pathogens (including Salmonella, Shigella, Yersinia, Aeromonas, Plesiomonas, or Campylobacter). Clostridium difficile toxin, ova, or parasites present. Systemic or rectal corticosteroid use within 4 weeks prior to the Screening Visit. Topical, intranasal, or inhaled use is not exclusionary. Immunomodulator (6-mercaptopurine, azathioprine) use within 6 weeks prior to the Screening Visit. History of biologic (eg, anti-tumor necrosis factor agents, integrin receptor antagonists) use at any time. Antibiotic use within 7 days prior to the Screening Visit. Any anti-inflammatory drugs, not including 5-ASA treatment but including non-steroidal anti-inflammatory drugs such as aspirin, COX-2 inhibitors or ibuprofen, within 7 days prior to the Screening Visit unless used at over-the-counter levels for <3 days. However, prophylactic use of a stable dose of aspirin up to 325mg/day for cardiac disease is permitted. Prebiotic/probiotic use within 7 days prior to the Screening Visit. Yogurt products are permitted.

Ages Eligible for Study
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Minimum Age: 5 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MMX Mesalamine/Mesalazine (Low Dose)<br>Once daily, tablets - the amount depends on the participants weight; 900 milligram per day (mg/day) for participants weighing 18 kg to less than or equal to (<=) 23 kilograms (kg); 1200 mg/day for participants weighing greater than (>) 23 kg to <= 35 kg; 1800 mg/day for participants weighing > 35 kg to <= 50 kg; 2400 mg/day for participants weighing > 50 kg to <= 90 kg. | Drug: MMX Mesalamine/Mesalazine (Low Dose)<br>* Once daily, tablets - the amount depends on the participants weight; 900 milligram per day (mg/day) for participants weighing 18 kg to less than or equal to (<=) 23 kilograms (kg); 1200 mg/day for participants weighing greater than (>) 23 kg to <= 35 kg; 1800 mg/day for participants weighing > 35 kg to <= 50 kg; 2400 mg/day for participants weighing > 50 kg to <= 90 kg.<br>* Other names: Mezavant;|
| Experimental: MMX Mesalamine/Mesalazine (High Dose)<br>Once daily, tablets - the amount depends on the participants weight;1800 mg/day for participants weighing 18 kg to <= 23 kg; 2400 mg/day for participants weighing > 23 kg to <= 35 kg; 3600 mg/day for participants weighing > 35 kg to <= 50 kg; 4800 mg/day for participants weighing > 50 kg to <= 90 kg. | Drug: MMX Mesalamine/Mesalazine (High Dose)<br>* Once daily, tablets - the amount depends on the participants weight;1800 mg/day for participants weighing 18 kg to <= 23 kg; 2400 mg/day for participants weighing > 23 kg to <= 35 kg; 3600 mg/day for participants weighing > 35 kg to <= 50 kg; 4800 mg/day for participants weighing > 50 kg to <= 90 kg.<br>* Other names: Lialda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Clinical Response During Double-Blind Acute Phase at Week 8 | Clinical response was defined as partial ulcerative colitis disease activity index (UC-DAI) score < or =1 with rectal bleeding = 0, stool frequency < or =1, and physician's global assessment (PGA = 0). Number of participants with clinical response were reported. | Week 8 | 
| Number of Participants With Clinical Response During Double-blind Maintenance Phase at Week 26 | Clinical response was defined as partial UC-DAI <=1 with (rectal bleeding = 0, stool frequency < or =1, and PGA = 0). Number of participants who had maintained clinical response were reported. | Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Clinical and Endoscopic Response During Double Blind Acute Phase at Week 8 Using Central Reading | Clinical and endoscopic response was defined as UC-DAI <=2 with rectal bleeding = 0 and stool frequency <=1, and PGA = 0, and with mucosal healing (endoscopy score <=1) at least a 1 point reduction in endoscopy score from baseline based on central reading. Participants with missing data at week 8 were assumed not to had a clinical response. Participants who completed week 8 but did not have central reading endoscopies at both baseline and week 8 were excluded. Number of participants with clinical and endoscopic response were reported. | Week 8 | 
| Number of Participants With Clinical and Endoscopic Response During Double Blind Acute Phase at Week 8 Using Local Reading | Clinical and endoscopic response was defined as UC-DAI < or =2 with rectal bleeding = 0 and stool frequency < or =1, and PGA = 0, and with mucosal healing (endoscopy score < or =1) at least a 1 point reduction in endoscopy score from baseline based on local reading. Participants with missing data at week 8 were assumed not to had a clinical response. Participants who completed week 8 but did not have local reading endoscopies at both baseline and week 8 were excluded. Number of participants with clinical and endoscopic response were reported. | Week 8 | 
| Change From Baseline in Daily Ulcerative Colitis Scale (DUCS) Score During Double-Blind Acute Phase | DUCS score was to measure 7 specific signs or symptom and one impact (abdominal pain, nocturnal stool, daytime stool, blood in stool, diarrhea, urgency, tiredness) of UC with each item score ranged from 0 (worst) to 10 (best) with the overall score ranged from 0 (worst) to 70 (best) based on the responses. Change in the DUCS score from baseline to Week 8 during DBA phase were reported. | Baseline to Week 8 | 
| Number of Participants With Improvement in Pediatric Ulcerative Colitis Activity Index (PUCAI) Score During Double-blind Acute Phase at Week 8 | PUCAI was a physician-administered measure that focuses on 6 key signs and symptoms of UC and activity limitations producing a total score ranging from 0-85 with higher scores being worse. Recommended cut-off scores to differentiate disease activity are < 10 (remission); 11-30 (mild); 31-64 (moderate) and > 65 (severe). Participants with an improvement (change of greater than or equal to [> or =] 20 points) in PUCAI score. Number of participants with improvement in PUCAI score during Double-blind Acute Phase at Week 8 were reported. | Week 8 | 
| Number of Participants With Clinical and Endoscopic Response During Double-Blind Maintenance Phase at Week 26 Using Central Reading | Clinical and endoscopic response was defined as UC-DAI < or =2 with rectal bleeding=0, stool frequency < or =1, PGA=0, and with mucosal healing (endoscopy score < or =1) based on central reading at Week 26. Number of participants with clinical and endoscopic response during double-blind maintenance phase at Week 26 using central reading were reported. | Week 26 | 
| Number of Participants With Clinical and Endoscopic Response During Double-Blind Maintenance Phase at Week 26 Using Local Reading | Clinical and endoscopic response was defined as UC-DAI < or = 2 with rectal bleeding=0, stool frequency < or = 1, PGA=0, and with mucosal healing (endoscopy score < or = 1) based on local reading. Number of participants who had maintained clinical and endoscopic response during double-blind maintenance phase at week 26 using local reading were reported. | Week 26 | 
| Change From Baseline in Daily Ulcerative Colitis Scale (DUCS) Score During Double-Blind Maintenance Phase | DUCS score was to measure 7 specific signs or symptom and one impact (abdominal pain, nocturnal stool, daytime stool, blood in stool, diarrhea, urgency, tiredness) of UC with each score range from 0 (worst) to 10 (best) with the overall score ranging from 0 (worst) to 70 (best) based on the responses. Change from Baseline in DUCS score during double-blind maintenance phase at week 13 and Week 26 wwere reported. | Baseline, Week 13, and Week 26 | 
| Number of Participants With Remission at Pediatric Ulcerative Colitis Activity Index (PUCAI) Score During Double-Blind Maintenance Phase at Week 26 | PUCAI was a physician-administered measure that focuses on 6 key signs and symptoms of UC and activity limitations producing a total score ranging from 0-85 with higher scores being worse. Recommended cut-off scores to differentiate disease activity are < 10 (remission); 11-30 (mild); 31-64 (moderate) and > 65 (severe). Number of participants with remission at PUCAI score during double-blind maintenance phase at week 26 were reported. | Week 26 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mild, Moderate