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

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

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.

Study Overview

• Status: Completed
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Drug: MMX mesalamine/ mesalazine

• Study Type: Interventional
• Enrollment (Actual): 759
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Bonheiden, Belgium, 2820
    • Imelda General Hospital
  • Kortrijk, Belgium, 8500
    • Vzw Az Groeninge
  • Roeselare, Belgium, 8800
    • Heilig Hart ziekenhuis vzw Roeselare-Menen
• Canada
  • Quebec, Canada, G1S 4L8
    • CHAUQ- Hopital du Saint-Sacrement
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • McMaster University Medical Centre
    • Toronto, Ontario, Canada, M3N 2V7
      • Toronto Digestive Disease Associates, Inc.
  • Quebec
    • Montreal, Quebec, Canada, H3A 1A1
      • Royal Victoria Hospital
    • Quebec City, Quebec, Canada, G2B 5S1
      • Alpha Recherche Clinique
• Colombia
  • Antioquia
    • Medellin, Antioquia, Colombia
      • Hospital Pablo Tobon Uribe
    • Medellin, Antioquia, Colombia
      • Promotora Medica Las Americas S.A.
  • Atlantico
    • Barranquilla, Atlantico, Colombia
      • Ugasend S.A.
  • Cundinamarca
    • Bogota, Cundinamarca, Colombia
      • FOQUS, Centro de Investigacion Clinica
• Czechia
  • Ceske Budejovice, Czechia, 37001
    • Private Gastroenterology Centre
  • Ceske Budejovice, Czechia, 390 01
    • Derma Plus s.r.o. Gastroenterology
  • Hradec Kralove, Czechia, 50012
    • Hepato-Gastroenterology HK s.r.o.
  • Jablonec nad Nisou, Czechia, 46660
    • Nemocnice Jablonec nad Nisou
  • Plzen, Czechia, 30460
    • Faculty hospital Plzen- Lochotin
  • Prague, Czechia, 14021
    • IKEM (Institute klinicke a experimentalni mediciny)
  • Prague 7, Czechia, 17004
    • Klinicke Centrum ISCARE I.V.F.
  • Tabor, Czechia, 39003
    • Nemocnice Tabor a.s.
  • Usti nad Labem, Czechia, 40113
    • Massarykova Nemocnice-Masaryk Hospital
  • Usti nad Orlici, Czechia, 56218
    • Orlickoustecka nemocnice a.s. (Hospital)
• France
  • Bordeaux, France, 33075
    • Hôpital Saint André
  • Clermont-Ferrand, France, 63003
    • CHU Estaing
  • Nantes, France, 44000
    • CHU Nantes- Hôtel Dieu
• Germany
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover/ Zentrum Innere Medizin/Gastroenterologie
  • Lueneburg, Germany, 21339
    • Stawdtisches Klinikum Lueneburg Gastroenterologie
• Hungary
  • Debrecen, Hungary, H-4032
    • Debreceni Egyetem Orvos-es Egeszsegtudomanyi Centrum III. sz. Belgyogyazati Klinika
  • Gyula, Hungary, 5700
    • Bekes Megyei Kepviselotestulet Pandy Kalman Korhaza, Endoszkopos laboratorium
  • Miskolc, Hungary, H-3526
    • Borsod-Abauj-Zemplen Megyei Korhaz es Egyrtrmi Oktato Korhaz, II. Belgyogyaszat
  • Mosonmagyarovar, Hungary, 9200
    • Karolina Korhaz, Belgyogyaszat es Gasztroenterologia
  • Vac, Hungary, H-2600
    • Javorszky Odon Varosi Korhaz, Gasztroenterologia
• India
  • Andhra Pradesh
    • Hyderabad, Andhra Pradesh, India, 500082
      • Asian institute of Gastroenterology
    • Visakhapatnam, Andhra Pradesh, India, 530002
      • Manikya Institute of Gastroenterology & Hepatology
  • Assam
    • Guwahati, Assam, India, 781006
      • Institute of Digestive & Liver Diseases
  • Gujarat
    • Ahmedabad, Gujarat, India, 380006
      • Mehta Hospital
  • Kamataka
    • Mangalore, Kamataka, India, 575001
      • Kasturba Medical College Hospital
  • Kerala
    • Thiruvananthapuram, Kerala, India, 695607
      • Sree Gokulam Medical College and Research Foundation
  • Maharashtra
    • Nagpur, Maharashtra, India, 440 012
      • Gastroenterology & Endoscopy Centre
    • Pune, Maharashtra, India, 411004
      • Sahyandri Speciality Hospital
    • Pune, Maharashtra, India, 411030
      • Poona Hospital & Research Centre
  • Punjab
    • Ludhiana, Punjab, India, 141001
      • Dayanand Medical College and Hospital
  • Rajasthan
    • Jaipur, Rajasthan, India, 302001
      • S R Kalla Memorial Gastro & General Hospital
    • Jaipur, Rajasthan, India, 302017
      • Dr. Nijhawan Clinic
  • UP
    • Lucknow, UP, India, 226003
      • Chhatrapati Shahuji Maharaj Medical University
• Ireland
  • Dublin, Ireland, 9
    • Beaumont Hospital
  • Dublin, Ireland, 24
    • Adelaide and Meath Hospital
  • Dublin, Ireland, 4
    • St Vincents' University Hospital
• Poland
  • Lodz, Poland, 90-302
    • NZOZ Centrum Medyczne Szpital Sw. Rodziny
  • Poznan, Poland, 61-485
    • NZOZ Centrum Medyczne HCP
  • Sopot, Poland, 81-756
    • Endoskopia Sp z o.o.
  • Torun, Poland, 80-100
    • Indyw. Spec. Prakt. Lek. w Dziedzinie Chirurgii Ogolnej i Gastroenterologii
  • Warszawa, Poland, 03-580
    • NZOZ Vivamed
  • Wroclaw, Poland, 50-023
    • LexMedica
  • Wroclaw, Poland, 54-144
    • EMC Instytut Medyczny SA
• Romania
  • Bucharest, Romania, 022328
    • Institutul Clinic Fundeni
  • Bucharest, Romania, 020475
    • Clinical Hospital "Dr. I. Cantacuzino"
  • Bucharest, Romania, 050098
    • Emergency University Clinical Hospital Bucuresti
  • Timisoara, Romania, 300002
    • Policlinic Algomed SRL
  • Timisoara, Romania, 300593
    • Policlinica "Dr. Citu" SRL
  • Mures
    • Targu Mures, Mures, Romania, 540461
      • CMI de Gastroenterologie
• South Africa
  • Port Elizabeth, South Africa, 6057
    • Greenacres Hospital
  • Free State
    • Bloemfontein, Free State, South Africa, 9301
      • Rose Park Hospital Boanerges CC Trials
  • KwaZulu Natal
    • Durban, KwaZulu Natal, South Africa, 4091
      • Parklands Medical Centre
  • KwaZulu- Natal
    • Durban, KwaZulu- Natal, South Africa, 4001
      • St. Augustine's Hospital
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7708
      • Kingsbury Hospital
    • Cape Town, Western Cape, South Africa, 7500
      • Panorama Medi-Clinic
    • Cape Town, Western Cape, South Africa, 7530
      • Louis Leipoldt Medical Centre
• Spain
  • Madrid, Spain, 28006
    • Hospital Universitario La Princesa
• United Kingdom
  • Middlesex
    • Harrow, Middlesex, United Kingdom, HA1 3UJ
      • St Mark's Hospital
  • Oxfordshire
    • Headington, Oxfordshire, United Kingdom, OX3 9DU
      • John Radcliffe Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Birmingham Gastroenterology Associates, PC
  • California
    • Anaheim, California, United States, 92801
      • Advanced Clinical Research Institute
    • Garden Grove, California, United States, 92840
      • Digestive & Liver Disease Specialists
    • Long Beach, California, United States, 90822
      • Long Beach VA Medical Center
    • San Diego, California, United States, 92103
      • Clinical Applications Laboratories, Inc.
  • Connecticut
    • Bristol, Connecticut, United States, 06010
      • Conneticut Gastroenterolgy Institute
  • Florida
    • Jacksonville, Florida, United States, 32256
      • Borland-Groover Clinic
    • New Smyrna Beach, Florida, United States, 32168
      • United Medical Research
    • Palm Harbor, Florida, United States, 34684
      • Advances Gastroenterology Associates
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Atlanta Gastroenterology Associates, Llc
    • Marietta, Georgia, United States, 30067
      • Atlanta Gastroenterology Associates
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
    • Moline, Illinois, United States, 61265
      • Midwest Clinical Research Associates
  • Iowa
    • Davenport, Iowa, United States, 52807
      • Gastrointestinal Clinic of Quad Cities
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • New Orleans Research Institute
    • Monroe, Louisiana, United States, 71201
      • Delta Research Partners
    • Shreveport, Louisiana, United States, 71103
      • Louisiana Research Center, LLC
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • Digestive Disorders Associates
    • Baltimore, Maryland, United States, 21229
      • Digestive Disease Associates
  • Michigan
    • Troy, Michigan, United States, 48098
      • Center for Digestive Health
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Mexico, Missouri, United States, 65265
      • Center for Digestive & Liver Disease, Inc.
  • New York
    • Great Neck, New York, United States, 11021
      • Long Island Clinical Research Associates, LLP
    • Setauket, New York, United States, 11733
      • Gastrointestinal Research Associates
  • North Carolina
    • Greensboro, North Carolina, United States, 27402
      • LeBauer Research Associates
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Ohio Gastroenterolgy and Liver Intstitute
  • Pennsylvania
    • Lancaster, Pennsylvania, United States, 17604
      • Regional Gastroenterology Associates of Lancaster, Ltd.
  • Tennessee
    • Kingsport, Tennessee, United States, 37660
      • Gastroenterology Associates, LLC
  • Texas
    • Houston, Texas, United States, 77090
      • S.D. Khan
    • San Antonio, Texas, United States, 78229
      • Gastroenterology Clinic of San Antonio, PA
  • Utah
    • Sandy, Utah, United States, 84070
      • Colon and Rectal Disease Center
    • Sandy, Utah, United States, 84094
      • Physicians Research Option, LLC
  • Virginia
    • Alexandria, Virginia, United States, 22304
      • Alexandria Clinical Research
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Wisconsin Center for Advances Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MMX mesalamine/ mesalazine	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects in Complete Remission at Month 12 of Maintenance Phase	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).	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects in Clinical Remission at Month 12 of Maintenance Phase	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).	12 months
Relapse in Ulcerative Colitis at Month 12 of Maintenance Phase	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.	12 months
Percentage of Subjects With Mucosal Healing at 12 Months of Maintenance Phase	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).	12 months
Improvement in Rectal Bleeding Score During the Acute Phase	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).	3 and 8 weeks
Improvement in Stool Frequency Symptoms During the Acute Phase	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).	3 and 8 weeks
Percentage of Subjects in Complete Remission at Week 8 of Acute Phase	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).	8 Weeks
Percentage of Subjects in Partial Remission at Week 8 of Acute Phase	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).	8 weeks

Collaborators and Investigators

• Sponsor: Shire

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 29, 2010
• Primary Completion (Actual): December 7, 2012
• Study Completion (Actual): December 7, 2012

Study Registration Dates

• First Submitted: May 13, 2010
• First Submitted That Met QC Criteria: May 13, 2010
• First Posted (Estimate): May 14, 2010

Study Record Updates

• Last Update Posted (Actual): June 9, 2021
• Last Update Submitted That Met QC Criteria: May 25, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Mesalamine
• Other Study ID Numbers: SPD476-409; 2009-017044-13 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)