Ability to Maintain or Achieve Clinical and Endoscopic Remission With MMX Mesalamine Once Daily in Adults With Ulcerative Colitis

• ClinicalTrials.gov Identifier: NCT01124149
• Recruitment Status: Completed
• First Posted: May 14, 2010
• Results First Posted: December 2, 2013
• Last Update Posted: June 9, 2021
• Sponsor: Shire
• Information provided by (Responsible Party): Takeda ( Shire )

Tracking Information

• First Submitted Date: May 13, 2010
• First Posted Date: May 14, 2010
• Results First Submitted Date: September 30, 2013
• Results First Posted Date: December 2, 2013
• Last Update Posted Date: June 9, 2021
• Actual Study Start Date: June 29, 2010
• Actual Primary Completion Date: December 7, 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 25, 2021)

Percentage of Subjects in Complete Remission at Month 12 of Maintenance Phase [ Time Frame: 12 months ]

Complete remission was defined as a modified Ulcerative Colitis Disease Activity Index (UC-DAI) <=1 with a score of 0 for rectal bleeding and stool frequency and at least a 1-point reduction in endoscopy score from baseline. The modified UC-DAI score is the sum of the scores of 4 parameters (stool frequency, rectal bleeding, endoscopy score, and physician global assessment), each scoring between 0 and 3, making 12 the worst score. Endoscopy score (mucosal appearance) ranges from 0-3 (0 = normal, 1 = mild , 2 = moderate, 3 = severe). Rectal bleeding is assessed on a scale from 0-3 (0 = no rectal bleeding, 1 = streaks of blood, 2 = obvious blood, 3 = mostly blood). Stool frequency is assessed on a scale of 0-2 (0 = 0-1 more than normal per day, 1 = 2-3 more than normal per day, 2 = 4 or more than normal per day).

• Original Primary Outcome Measures (submitted: May 13, 2010): Score on ulcerative colitis (UC) rating scale [ Time Frame: 12 months ]

Current Secondary Outcome Measures (submitted: May 25, 2021)

• Percentage of Subjects in Clinical Remission at Month 12 of Maintenance Phase [ Time Frame: 12 months ]
  Clinical remission was defined as a score of 0 for rectal bleeding and stool frequency. Rectal bleeding is assessed on a scale from 0-3 (0 = no rectal bleeding, 1 = streaks of blood, 2 = obvious blood, 3 = mostly blood). Stool frequency is assessed on a scale of 0-2 (0 = 0-1 more than normal per day, 1 = 2-3 more than normal per day, 2 = 4 or more than normal per day).
• Relapse in Ulcerative Colitis at Month 12 of Maintenance Phase [ Time Frame: 12 months ]
  Relapse was defined in the Maintenance Phase as the need for alternative treatment for UC (including surgery); subjects were classified as having a relapse if they had withdrawn from the study due to a lack of efficacy.
• Percentage of Subjects With Mucosal Healing at 12 Months of Maintenance Phase [ Time Frame: 12 months ]
  Subjects with mucosal healing were defined as subjects who had an endoscopy score <=1. Endoscopy score (mucosal appearance) ranges from 0-3 (0 = normal, 1 = mild , 2 = moderate, 3 = severe).
• Improvement in Rectal Bleeding Score During the Acute Phase [ Time Frame: 3 and 8 weeks ]
  Improvement was defined as at least a 1-point reduction in the rectal bleeding score from baseline at each assessment point. Rectal bleeding is assessed on a scale from 0-3 (0 = no rectal bleeding, 1 = streaks of blood, 2 = obvious blood, 3 = mostly blood).
• Improvement in Stool Frequency Symptoms During the Acute Phase [ Time Frame: 3 and 8 weeks ]
  Improvement was defined as at least a 1-point reduction in the stool frequency score from baseline at each assessment point. Stool frequency is assessed on a scale of 0-2 (0 = 0-1 more than normal per day, 1 = 2-3 more than normal per day, 2 = 4 or more than normal per day).
• Percentage of Subjects in Complete Remission at Week 8 of Acute Phase [ Time Frame: 8 Weeks ]
  Complete (clinical and endoscopic) remission was defined as a modified UC-DAI <=1 with a score of 0 for rectal bleeding and stool frequency and at least a 1-point reduction in endoscopy score from baseline. The modified UC-DAI score is the sum of the scores of 4 parameters (stool frequency, rectal bleeding, endoscopy score, and physician global assessment), each scoring between 0 and 3, making 12 the worst score. Endoscopy score (mucosal appearance) ranges from 0-3 (0 = normal, 1 = mild , 2 = moderate, 3 = severe). Rectal bleeding is assessed on a scale from 0-3 (0 = no rectal bleeding, 1 = streaks of blood, 2 = obvious blood, 3 = mostly blood). Stool frequency is assessed on a scale of 0-2 (0 = 0-1 more than normal per day, 1 = 2-3 more than normal per day, 2 = 4 or more than normal per day).
• Percentage of Subjects in Partial Remission at Week 8 of Acute Phase [ Time Frame: 8 weeks ]
  Partial remission was defined as a modified UC-DAI <=3 with a combined stool frequency and rectal bleeding score of <=1 and not in complete remission. The modified UC-DAI score is the sum of the scores of 4 parameters (stool frequency, rectal bleeding, endoscopy score, and physician global assessment), each scoring between 0 and 3, making 12 the worst score. Endoscopy score (mucosal appearance) ranges from 0-3 (0 = normal, 1 = mild , 2 = moderate, 3 = severe). Rectal bleeding is assessed on a scale from 0-3 (0 = no rectal bleeding, 1 = streaks of blood, 2 = obvious blood, 3 = mostly blood). Stool frequency is assessed on a scale of 0-2 (0 = 0-1 more than normal per day, 1 = 2-3 more than normal per day, 2 = 4 or more than normal per day).

Original Secondary Outcome Measures (submitted: May 13, 2010)

• To compare the percentage of subjects in clinical remission at 12 months between subjects who were in complete remission and subjects who were in partial remission at the end of 8 weeks acute treatment. [ Time Frame: 12 months ]
• To compare the time to relapse between subjects who were in complete remission and subjects who were in partial remission at the end of 8 weeks acute treatment. [ Time Frame: 12 months ]
• Compare percent of subjects who achieve or maintain mucosal healing (endoscopy score less than or equal to 1) at 12 months between subjects who were in complete remission and subjects who were in partial remission at the end of 8 weeks acute treatment. [ Time Frame: 12 months ]
• To assess the improvement in symptoms at 3 and 8 weeks of acute treatment. [ Time Frame: 3 and 8 weeks ]
• To assess the percentage of subjects who achieve complete remission at the end of 8 weeks acute treatment. [ Time Frame: 8 weeks ]
• To assess the safety and tolerability of MMX mesalamine/mesalazine. [ Time Frame: Ongoing ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Ability to Maintain or Achieve Clinical and Endoscopic Remission With MMX Mesalamine Once Daily in Adults With Ulcerative Colitis
• Official Title: A Phase 4, Open-label, Multicenter, Prospective Study to Evaluate the Effect of Remission Status on the Ability to Maintain or Achieve Clinical and Endoscopic Remission During a 12-Month, Long-term Maintenance Phase With 2.4g/Day MMX Mesalamine/Mesalazine Once Daily in Adult Subjects With Ulcerative Colitis
• Brief Summary: This study was designed to evaluate if subjects who achieve complete remission after 8 weeks of acute therapy with MMX mesalamine/mesalazine 4.8g/day given QD have better long-term outcomes and remain in remission longer compared with subjects who demonstrate only partial remission after acute therapy with MMX mesalamine/mesalazine 4.8g/day given QD. Therefore, subjects who achieve either complete or partial remission will enter into a 12-month maintenance phase, during which they will receive MMX mesalamine/mesalazine 2.4g/day given QD. Remission status for the 2 groups will be evaluated and compared at the end of this 12-month maintenance period. The data obtained from this study will provide scientifically meaningful information to demonstrate that achieving complete remission (clinical and endoscopic remission) is important for a better long-term prognosis, or that the current paradigm of symptomatic treatment is appropriate.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Ulcerative Colitis

Intervention

Drug: MMX mesalamine/ mesalazine

4.8g/day given QD (four 1.2g tablets) for 8 weeks, 2.4g/day given QD (two 1.2g tablets) for 12 months

Other Names:

• Lialda
• Mezavant
• Mezavant XL
• Mezavant LP

Study Arms

Experimental: MMX mesalamine/ mesalazine

Intervention: Drug: MMX mesalamine/ mesalazine

Publications *

• Stevens TW, Gecse K, Turner JR, de Hertogh G, Rubin DT, D'Haens GR. Diagnostic Accuracy of Fecal Calprotectin Concentration in Evaluating Therapeutic Outcomes of Patients With Ulcerative Colitis. Clin Gastroenterol Hepatol. 2021 Nov;19(11):2333-2342. doi: 10.1016/j.cgh.2020.08.019. Epub 2020 Aug 13.
• Willian MK, D'Haens G, Yarlas A, Joshi AV. Changes in health-related quality of life and work-related outcomes for patients with mild-to-moderate ulcerative colitis receiving short-term and long-term treatment with multimatrix mesalamine: a prospective, open-label study. J Patient Rep Outcomes. 2018 Apr 27;2:22. doi: 10.1186/s41687-018-0046-5. eCollection 2018 Dec.
• Yarlas A, D'Haens G, Willian MK, Teynor M. Health-Related Quality of Life and Work-Related Outcomes for Patients With Mild-to-Moderate Ulcerative Colitis and Remission Status Following Short-Term and Long-Term Treatment With Multimatrix Mesalamine: A Prospective, Open-Label Study. Inflamm Bowel Dis. 2018 Jan 18;24(2):450-463. doi: 10.1093/ibd/izx041.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 8, 2019): 759
• Original Estimated Enrollment (submitted: May 13, 2010): 695
• Actual Study Completion Date: December 7, 2012
• Actual Primary Completion Date: December 7, 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Adults aged 18 or older
2. Male, or non-pregnant, non-lactating female who agrees to comply with any applicable contraceptive requirements of the protocol
3. Diagnosis of active mild to moderate UC (acute flare or newly diagnosed)
4. Stable maintenance therapy of 5-ASA less than or equal to 3.2 g/day (excluding MMX mesalamine/mesalazine), if 5-ASA is being taken at the onset of acute flare.

Exclusion Criteria:

1. Severe UC
2. Acute flare with onset greater than >6 weeks prior to baseline while on maintenance therapy. There is no limit to the onset of flare prior to baseline if the flare is untreated.
3. Acute flare while on maintenance MMX mesalamine/mesalazine (Lialda, Mezavant, Mezavant XL, Mezavant LP)
4. Unsuccessfully treated current acute flare using steroids or 5-ASA doses >3.2 g/day
5. Acute flare on a 5-ASA maintenance therapy of >3.2 g/day
6. Systemic or rectal steroids use within the 4 weeks prior to screening or immunosuppressants within the last 6 weeks prior to screening
7. History of biologic (anti-TNF agent) use
8. Antibiotic use or repeated use (>3 consecutive days of use at doses above the prescribed over-the-counter dose) of any anti-inflammatory drugs, including non-steroidal anti-inflammatory drugs such as aspirin, COX-2 inhibitors or ibuprofen, within 7 days prior to screening. However, prophylactic use of a stable dose of aspirin up to 325mg/day for cardiac disease is permitted
9. Current or recurrent disease, other than UC, that could affect the colon, the action, absorption, or disposition of the IMP, or clinical or laboratory assessments

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Canada, Colombia, Czechia, France, Germany, Hungary, India, Ireland, Poland, Romania, South Africa, Spain, United Kingdom, United States
• Removed Location Countries: Brazil, Czech Republic

Administrative Information

• NCT Number: NCT01124149
• Other Study ID Numbers: SPD476-409; 2009-017044-13 ( EudraCT Number )
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• URL: https://vivli.org/ourmember/takeda/

• Current Responsible Party: Takeda ( Shire )
• Original Responsible Party: Timothy Whitaker, M.D., Shire Pharmaceutical
• Current Study Sponsor: Shire
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Study Director; Takeda

• PRS Account: Takeda
• Verification Date: May 2021