Clinical trial NCT02093663: Safety and Efficacy of MMX Mesalamine/Mesalazine in Pediatric Subjects With Mild to Moderate Ulcerative Colitis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Ulcerative Colitis
Keywords: Mild
Moderate
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2014-03-21
Enrollment: 107
Sex: ALL
Minimum age (years): 5
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Clinical Response During Double-Blind Acute Phase at Week 8
timeFrame: Week 8
measure: Number of Participants With Clinical Response During Double-blind Maintenance Phase at Week 26
timeFrame: Week 26
Secondary outcomes:
measure: Number of Participants With Clinical and Endoscopic Response During Double Blind Acute Phase at Week 8 Using Central Reading
timeFrame: Week 8
measure: Number of Participants With Clinical and Endoscopic Response During Double Blind Acute Phase at Week 8 Using Local Reading
timeFrame: Week 8
measure: Change From Baseline in Daily Ulcerative Colitis Scale (DUCS) Score During Double-Blind Acute Phase
timeFrame: Baseline to Week 8
measure: Number of Participants With Improvement in Pediatric Ulcerative Colitis Activity Index (PUCAI) Score During Double-blind Acute Phase at Week 8
timeFrame: Week 8
measure: Number of Participants With Clinical and Endoscopic Response During Double-Blind Maintenance Phase at Week 26 Using Central Reading
timeFrame: Week 26
measure: Number of Participants With Clinical and Endoscopic Response During Double-Blind Maintenance Phase at Week 26 Using Local Reading
timeFrame: Week 26
measure: Change From Baseline in Daily Ulcerative Colitis Scale (DUCS) Score During Double-Blind Maintenance Phase
timeFrame: Baseline, Week 13, and Week 26
measure: Number of Participants With Remission at Pediatric Ulcerative Colitis Activity Index (PUCAI) Score During Double-Blind Maintenance Phase at Week 26
timeFrame: Week 26
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: University of Maryland Children's Hospital
state: Maryland
city: Baltimore
country: United States
facility: John Hopkins
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Newton
country: United States
facility: Newton Wellesley Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota Children's Hospital
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Gastroenterology
state: Minnesota
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
city: Southlake
country: United States
facility: Texas Digestive Disease Consultants
state: Texas
city: Roanoke
country: United States
facility: Carilion Medical Center
state: Virginia
city: Edmonton
country: Canada
facility: University of Alberta Pediatric Gastroenterology & Nutrition
state: Alberta
city: Budapest
country: Hungary
facility: Szent Janos Korhaz És Észak-budai Egyesitett Korha
city: Gyula
country: Hungary
facility: Bekes Megyei Pandy Kalman Korhaz
city: Miskolc
country: Hungary
facility: Baz Megyei Korhaz Es Egyetemi Oktatokorhaz
city: Nyiregyhaza
country: Hungary
facility: Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktato Korhaz
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
city: Be'er Sheva
country: Israel
facility: Soroka Medical Center
city: Haifa
country: Israel
facility: Rambam Health Corporation
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Petach Tikva
country: Israel
facility: Schneider Medical Centre
city: Bialystok
country: Poland
facility: Uniwersytecki Dzieciecy Szpital Kliniczny im. Ludwika Zamenhofa
city: Krakow
country: Poland
facility: Klinika Pediatrii Gastroenterologii I Zywienia
city: Lodz
country: Poland
facility: Klinika Gastroenterologii I Pediatrii
city: Olsztyn
country: Poland
facility: Wojewodzki Specjalistyczny Szpital Dzieciecy
city: Rzeszow
country: Poland
facility: Gabinet Lekarski-Bartosz Korczowski
city: Warszawa
country: Poland
facility: Oddzial Gastroenterologii I Hepatologii
city: Wrocław
country: Poland
facility: Uniwersytecki Szpital Kliniczny We Wrocławiu
city: Banska Bystrica
country: Slovakia
facility: Detská fakultná nemocnica s poliklinikou
city: Bratislava
country: Slovakia
facility: University Children's Hospital
city: Martin
country: Slovakia
facility: Univerzitna Nemocnica Martin
city: Liverpool
country: United Kingdom
facility: Alder Hey Children's Hospital
city: London
country: United Kingdom
facility: Barts Health NHS Trust, Royal London Hospital
city: London
country: United Kingdom
facility: King's College Hospital
city: London
country: United Kingdom
facility: Great Ormond Street Hospital
Study officials:
affiliation: Takeda
name: Shire Director
role: STUDY_DIRECTOR
References: