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

Ulcerative Colitis Clinical Trial

— PACE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02093663
• Other study ID #: SPD476-319
• Secondary ID: 2013-001744-65
• Status: Completed
• Phase: Phase 3
• Start date: December 12, 2014
• Est. completion date: November 28, 2018

Study information

• Verified date: May 2021
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 107
• Est. completion date: November 28, 2018
• Est. primary completion date: November 28, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years to 17 Years

Eligibility

Inclusion Criteria:

1. 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.

2. Subject's parent/LAR demonstrates an understanding, ability, and willingness to fully comply with study procedures and restrictions.

3. Male and female children and adolescents aged 5-17 years, inclusive.

4. Body weight 18-90kg.

5. 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.

6. 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.

7. Subject is able to swallow the investigational product whole.

Double-blind Acute Phase:

8. 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.

9. 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:

10. Partial UC-DAI =1 (rectal bleeding=0, stool frequency =1, and PGA=0) at the Baseline Visit.

Exclusion Criteria:

1. Severe UC (defined by PGA=3).

2. Crohn's disease, bleeding disorders, active peptic ulcer disease, or UC known to be confined to the rectum (isolated rectal proctitis).

3. Asthma, only if known to be 5 ASA sensitive.

4. Positive stool culture for enteric pathogens (including Salmonella, Shigella, Yersinia, Aeromonas, Plesiomonas, or Campylobacter). Clostridium difficile toxin, ova, or parasites present.

5. Systemic or rectal corticosteroid use within 4 weeks prior to the Screening Visit. Topical, intranasal, or inhaled use is not exclusionary.

6. Immunomodulator (6-mercaptopurine, azathioprine) use within 6 weeks prior to the Screening Visit.

7. History of biologic (eg, anti-tumor necrosis factor agents, integrin receptor antagonists) use at any time.

8. Antibiotic use within 7 days prior to the Screening Visit.

9. 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.

10. Prebiotic/probiotic use within 7 days prior to the Screening Visit. Yogurt products are permitted.

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

Drug:
• MMX Mesalamine/Mesalazine (Low Dose)
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.
• MMX Mesalamine/Mesalazine (High Dose)
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.

Locations

Country	Name	City	State
Canada	University of Alberta Pediatric Gastroenterology & Nutrition	Edmonton	Alberta
Hungary	Szent Janos Korhaz És Észak-budai Egyesitett Korha	Budapest
Hungary	Bekes Megyei Pandy Kalman Korhaz	Gyula
Hungary	Baz Megyei Korhaz Es Egyetemi Oktatokorhaz	Miskolc
Hungary	Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktato Korhaz	Nyiregyhaza
Hungary	Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont	Szeged
Israel	Soroka Medical Center	Be'er Sheva
Israel	Rambam Health Corporation	Haifa
Israel	Shaare Zedek Medical Center	Jerusalem
Israel	Schneider Medical Centre	Petach Tikva
Poland	Uniwersytecki Dzieciecy Szpital Kliniczny im. Ludwika Zamenhofa	Bialystok
Poland	Klinika Pediatrii Gastroenterologii I Zywienia	Krakow
Poland	Klinika Gastroenterologii I Pediatrii	Lodz
Poland	Wojewodzki Specjalistyczny Szpital Dzieciecy	Olsztyn
Poland	Gabinet Lekarski-Bartosz Korczowski	Rzeszow
Poland	Oddzial Gastroenterologii I Hepatologii	Warszawa
Poland	Uniwersytecki Szpital Kliniczny We Wroclawiu	Wroclaw
Slovakia	Detská fakultná nemocnica s poliklinikou	Banska Bystrica
Slovakia	University Children's Hospital	Bratislava
Slovakia	Univerzitna Nemocnica Martin	Martin
United Kingdom	Alder Hey Children's Hospital	Liverpool
United Kingdom	Barts Health NHS Trust, Royal London Hospital	London
United Kingdom	Great Ormond Street Hospital	London
United Kingdom	King's College Hospital	London
United States	John Hopkins	Baltimore	Maryland
United States	University of Maryland Children's Hospital	Baltimore	Maryland
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	University of Minnesota Children's Hospital	Minneapolis	Minnesota
United States	Newton Wellesley Hospital	Newton	Massachusetts
United States	Carilion Medical Center	Roanoke	Virginia
United States	Mayo Clinic Gastroenterology	Rochester	Minnesota
United States	Texas Digestive Disease Consultants	Southlake	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Shire

Countries where clinical trial is conducted

United States,  Canada,  Hungary,  Israel,  Poland,  Slovakia,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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