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

NCT ID: NCT02093663

Last Updated: 2021-06-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 107 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-12-12
• Study Completion Date: 2018-11-28

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.

Conditions

Ulcerative Colitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

MMX Mesalamine/Mesalazine (Low Dose)

Intervention Type: DRUG

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.

Group Type: EXPERIMENTAL

MMX Mesalamine/Mesalazine (High Dose)

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Other Intervention Names

Lialda; Mezavant; Mezavant; Lialda

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.

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shire

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Shire Director

Role: STUDY_DIRECTOR

Takeda

Locations

University of Maryland Children's Hospital

Baltimore, Maryland, United States

John Hopkins

Baltimore, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Newton Wellesley Hospital

Newton, Massachusetts, United States

University of Minnesota Children's Hospital

Minneapolis, Minnesota, United States

Mayo Clinic Gastroenterology

Rochester, Minnesota, United States

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Texas Digestive Disease Consultants

Southlake, Texas, United States

Carilion Medical Center

Roanoke, Virginia, United States

University of Alberta Pediatric Gastroenterology & Nutrition

Edmonton, Alberta, Canada

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

Nyíregyháza, , Hungary

Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont

Szeged, , Hungary

Soroka Medical Center

Beersheba, , Israel

Rambam Health Corporation

Haifa, , Israel

Shaare Zedek Medical Center

Jerusalem, , Israel

Schneider Medical Centre

Petah Tikva, , Israel

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

Rzeszów, , Poland

Oddzial Gastroenterologii I Hepatologii

Warsaw, , Poland

Uniwersytecki Szpital Kliniczny We Wrocławiu

Wroclaw, , Poland

Detská fakultná nemocnica s poliklinikou

Banská Bystrica, , Slovakia

University Children's Hospital

Bratislava, , Slovakia

Univerzitna Nemocnica Martin

Martin, , Slovakia

Alder Hey Children's Hospital

Liverpool, , United Kingdom

Barts Health NHS Trust, Royal London Hospital

London, , United Kingdom

King's College Hospital

London, , United Kingdom

Great Ormond Street Hospital

London, , United Kingdom

Countries

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

References

Croft NM, Korczowski B, Kierkus J, Caballero B, Thakur MK. Safety and efficacy of multimatrix mesalamine in paediatric patients with mild-to-moderate ulcerative colitis: a phase 3, randomised, double-blind study. EClinicalMedicine. 2023 Oct 6;65:102232. doi: 10.1016/j.eclinm.2023.102232. eCollection 2023 Nov.

Reference Type: DERIVED

PMID: 37855022 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2013-001744-65

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

SPD476-319

Identifier Type: -

Identifier Source: org_study_id