Efficacy and Safety of Anti-MAP Therapy in Adult Crohn's Disease (MAPUS)

November 29, 2020 updated by: RedHill Biopharma Limited

A Randomized, Double Blind, Placebo-controlled, Multicenter, Parallel Group Study to Assess the Efficacy and Safety of Fixed-dose Combination RHB-104 in Subjects With Moderately to Severely Active Crohn's Disease

The investigators hypothesize that RHB-104 will have greater efficacy than placebo in Crohn's disease.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

A Randomized, Double Blind, Placebo-controlled, Multicenter, Parallel Group Study to Assess the Efficacy and Safety of Fixed-dose Combination RHB-104 in Subjects with Moderately to Severely Active Crohn's Disease.

Study Type

Interventional

Enrollment (Actual)

331

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • New South Wales
      • Bankstown, New South Wales, Australia, 2200
        • Bankstown Hospital, Level 3, Department of Gastroenterology, Eldridge Road
      • Concord, New South Wales, Australia, 2139
        • Department of Gastroenterology and Hepatology, Concord Hospital, Hospital Road
      • Kingswood, New South Wales, Australia, 2747
        • Nepean Hospital, Derby Street
      • Liverpool, New South Wales, Australia, 2170
        • Department of Gastroenterology, Level 1, Clinic 123, New Clinical Building, Liverpool Hospital, Elizabeth St.
    • Queensland
      • Herston, Queensland, Australia, 4029
        • Department of Gastroenterology and Hepatology, Level 9, Ned Hanlon Building, Royal Brisbane and Women's Hospital Corner Butterfield Street and Bowen Bridge Street
      • South Brisbane, Queensland, Australia, 4101
        • Mater Hospital Brisbane, Department of Gastroenterology, Raymond Terrace
    • Victoria
      • Ballarat, Victoria, Australia, 3350
        • Ballarat Health Services, Drummond St North
      • Box Hill, Victoria, Australia, 3128
        • Department of Gastroenterology, Eastern Health, ECRU, Level 2, 5 Arnold Street
      • Malvern, Victoria, Australia, 3144
        • Department of Gastroenterology and Hepatology, Cabrini Medical Centre, 183 Wattletree Road
      • Plovdiv, Bulgaria, 4002
        • MHAT "Sv. Karidad" EAD, Department of Internal Medicine / Gastroenterology, endocrinology and metabolic disorders, 23А, Nikola Vaptsarov Blvd
      • Sliven, Bulgaria, 8800
        • MHAT "Hadzhi Dimitar" OOD, Department of Internal Medicine / Gastroenterology and Endocrinology, 5, Dimitar Pehlivanov str.
      • Sofia, Bulgaria, 1432
        • UMHAT "Sv. Ivan Rilski" EAD; Clinic of Gastroenterology, 15, Akad. Ivan Geshov Blvd.,
      • Sofia, Bulgaria, 1784
        • ACIBADEM CITY CLINIC UNIVERSITY HOSPITAL EOOD, Oncology Center, Clinic of Gastroenterology, 66 A, Tsarigradsko shosse Blvd
      • Varna, Bulgaria, 9020
        • DCC "Mladost-M Varna" OOD, office 528 V, 15, Republika Blvd.
    • British Columbia
      • Victoria, British Columbia, Canada, V8T 5G4
        • Discovery Clinical Services Ltd. 601 A Discovery St.
    • Ontario
      • Toronto, Ontario, Canada, M5G 1X5
        • Mount Sinai Hospital, 600 University Avenue, Suite 445
    • Quebec
      • Montreal, Quebec, Canada, H3G 1A4
        • Montreal General Hospital Digestive Lab Research Institute McGill University Health Center, 1650 Cedar Avenue C10.145
    • Saskatchewan
      • Saskatoon, Saskatchewan, Canada, S7N 0W8
        • University of Saskatchewan Royal University Hospital, 103 Hospital Drive IBD Clinical Trials Unit Rm 2658
      • Horovice, Czechia, 268 31
        • Nemocnice Horovice, NH Hospital, a.s., Chirurgicke oddeleni, K Nemocnici 1106
      • Hradec Kralove, Czechia, 500 02
        • Gastroenterologie s.r.o., Manesova 646,
      • Hradec Kralove, Czechia, 50012
        • HEPATO-GASTROENTEROLOGIE HK, s.r.o., Trida Edvarda Benese 1549/34
      • Praha, Czechia, 17000
        • IBD centrum / ISCARE IVF a.s., Jankovcova 1569/2c
      • Praha 3, Czechia, 13000
        • EGK s.r.o., Sanatorium sv. Anny, Gastroenterologicke oddeleni, Lucni 7a/2776,
      • Trebovice, Czechia, 722 00
        • ARTROSCAN, s.r.o., Gastroenterologicka ambulance, 5114 Trebovicka, Ostrava
      • Usti nad Labem, Czechia, 401 13
        • Krajska zdravotni, a.s., Masarykova nemocnice o.z. Gastroenterologie, Socialni pece 3316/12A
      • Be'er Ya'aqov, Israel, 70300
        • Assaf HaRofeh Medical Center, Gastroenterology Department, Harofeh Medical Center
      • Haifa, Israel, 31048
        • Bnaizion Medical Center, Golomb 47
      • Holon, Israel, 58100
        • The E. Wolfson Medical Center, 62 Halohamim Str.
      • Jerusalem, Israel, 91031
        • Shaare Zedek Medical Center, Beith Street
      • Jerusalem, Israel, 91120
        • Ein Karem Medical Center, Kiryat Hadassah
      • Kfar-Saba, Israel, 44281
        • Meir, 59 Tchemacovsky St
      • Nahariya, Israel, 1210001
        • Galilee Medical Center, P.O.B. 21
      • Nazareth, Israel, 16100
        • Holy Family Hospital, Namsawi St. POB 8
      • Petach-Tikva, Israel, 49100
        • RMC Beilinson Hospital, 39 Jabotinsky Street
      • Tel Aviv, Israel, 64239
        • Sourasky Medical Center, 6 Weizman Street
      • Auckland, New Zealand, 0620
        • Shakespeare Specialist Group, North Shore, Suite 3, 181 Shakespeare Road, Milford Takapuna
      • Christchurch, New Zealand, 4710
        • Christchurch Hospital
      • Dunedin, New Zealand, 9054
        • Gastroenterology Unit, Southern District Health Board, 201 Great King Street,
      • Hamilton, New Zealand, 3240
        • Department of Gastroenterology,Waikato Hospital
      • Tauranga, New Zealand, 3112
        • Clinical Trials Unit, Tauranga Hospital,
      • Bialystok, Poland, 15-351
        • NZOZ Specjalistyczne Centrum Gastrologii GASTROMED Wiejska 81
      • Gdańsk, Poland, 80-104
        • SP ZOZ MSWiA w Gdańsku, Oddział Gastroenterologiczny, ul. Kartuska 4/6
      • Krakow, Poland, 31-271
        • UNICARDIA Specjalistyczne Centrum Leczenia Chorob Serca i Naczyn & UNIMEDICA Specjalistyczne Centrum Medyczne Sp. z o.o. Kluczborska 15
      • Olsztyn, Poland, 10-561
        • Wojewodzki Szpital Kliniczny w Olsztynie Oddzial Gastroenterologiczny Żołnierska 18
      • Sopot, Poland, 81-756
        • ENDOSKOPIA sp. z o.o. B. Chrobrego 6/8
      • Szczecin, Poland, 70-111
        • EuroMedis sp. z.o.o., ul. Powstanców Wielkopolskich 33a
      • Torun, Poland, 87-100
        • "GASTROMED" Kopon, Zmudzinski i wspolnicy sp. j., Specjalistyczne Centrum Gastroskopii i Endoskopii, Specjalistyczne Gabinety Lekarskie Grudziadzka 11
      • Warszawa, Poland, 02-507
        • Centralny Szpital Kliniczny MSW w Warszawie Klinika Chorob Wewnetrznych i Gastroenterologii Woloska 137
      • Wroclaw, Poland, 53-333
        • ARS MEDICA s.c. Rybak Maria, Rybak Zbigniew, Powstancow Slaskich 56A/2
      • Łódź, Poland, 90-302
        • Centrum Medyczne Szpital Sw. Rodziny Sp. z o.o. Wigury 19
      • Belgrade, Serbia, 11000
        • : Clinic for Gastroenterology and Hepatology, Clinical Center of Serbia Koste Todorovica 2
      • Belgrade, Serbia, 11000
        • Clinical Department of Gastroenterology and Hepatology, Clinic for Internal Diseases, Clinical Hospital Center Zvezdara Dimitrija Tucovica 161
      • Belgrade, Serbia, 11080
        • Department of Gastroenterology and Hepatology, Clinical Hospital Center Zemun Vukova 9
      • Kragujevac, Serbia, 34000
        • : Center for Gastroenterohepatology, Clinic for Internal Medicine, Clinical Center of Kragujevac Zmaj Jovina 30
      • Novi Sad, Serbia, 21000
        • : Clinic of Gastroenterology and Hepatology, Clinical Center of Vojvodina Hajduk Veljkova 1
      • Bratislava, Slovakia, 82606
        • Univerzitna nemocnica Bratislava - Nemocnica Ružinov, V. Interná klinika LFUK a UNB, Gastroenterologické a hepatologické oddelenie, Ruzinovska 6
      • Bratislava, Slovakia, 851 07
        • Univerzitná nemocnica Bratislava - Nemocnica sv. Cyrila a Metoda Gastroenterologická klinika SZU a UNB Antolská 11
      • Brezno, Slovakia, 97701
        • Breznianske centrum gastroenterologie, s.r.o. Banisko 1
      • Martin, Slovakia, 036 01
        • PIGEAS s.r.Prieložtek 1, o.,
      • Nitra, Slovakia, 949 01
        • KM Management spol. s.r.o., Gastroenterologické a hepatologické centrum Nitra, Špitálska 13
    • Arizona
      • Tucson, Arizona, United States, 85710
        • Del Sol Research Management, 850 N Knob Road
    • California
      • Anaheim, California, United States, 92801
        • Associated Gastroenterology Medical Group, 1211 W. La Palmak Ave, Suite 303
      • La Mirada, California, United States, 90638
        • Medvin Clinical Research, 15627 Imperial Highway,
      • San Carlos, California, United States, 94070
        • Digestive Care Associates, Inc., 1000 Laurel St.
      • Ventura, California, United States, 93003
        • Ventura Clinical Trials, 1835 Knoll Drive
    • Connecticut
      • Hamden, Connecticut, United States, 06518
        • Medical Research Center of Connecticut, LLC
    • Florida
      • Aventura, Florida, United States, 33180
        • Innovative Medical Research of South Florida, 2999 NE 191 St., Suite 330
      • Clearwater, Florida, United States, 33765
        • Clinical Research of West Florida
      • Lauderdale Lakes, Florida, United States, 33319
        • Sunrise Medical Research, Inc. 4700 N. State Road Building A, Suite 111
      • Naples, Florida, United States, 34102
        • Gastroenterology Group of Naples, 1064 Goodlette Road
      • New Port Richey, Florida, United States, 34653
        • Advanced Research Institute Inc., 7114 Congress Street
      • Orlando, Florida, United States, 32802
        • Endoscopic Research, Inc., 1817 North Mills Avenue
      • Port Orange, Florida, United States, 32127
        • Advanced Medical Research Center, 1690 Dunlawton Ave., Suite 110
    • Georgia
      • Decatur, Georgia, United States, 30033
        • Atlanta Center for Gastroenterology 2665 North Decatur Road Suite 550
      • Marietta, Georgia, United States, 30060
        • Gastrointestinal Specialists of Georgia PC, 711 Canton Rd. Suite 300
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
      • Urbana, Illinois, United States, 61801
        • The Carle Foundation, 611 West Park Street
    • Kansas
      • Topeka, Kansas, United States, 66606
        • Cotton-O'Neil Clinical Research Center, 720 SW Lane St.
    • Maryland
      • Annapolis, Maryland, United States, 21401
        • Investigative Clinical Research, 612 Ridgely Avenue, Suite 401,
      • Chevy Chase, Maryland, United States, 20815
        • Chevy Chase Clinical Research, 5550 Friendship Blvd.
    • Massachusetts
      • Brockton, Massachusetts, United States, 02302-2926
        • Commonwealth Clinical Studies, 189 Quincy St.
    • Michigan
      • Troy, Michigan, United States, 48098
        • Center for Digestive Health
      • Wyoming, Michigan, United States, 49519
        • West Michigan Clinical Research Center, 2093 Health Dr. SW, Suite 201
    • Missouri
      • Belton, Missouri, United States, 64012
        • Ehrhardt Clinical Research, LLC, 108 Congress Street
    • New Jersey
      • Egg Harbor Township, New Jersey, United States, 08324
        • AGA Clinical Research Associates, Inc., 3205 Fire Road
      • Teaneck, New Jersey, United States, 07666
        • Holy Name Medical Center, 718 Teaneck Road
    • New York
      • Bronx, New York, United States, 10467
        • Montefiore Medical Center, 111 East 210th Street
      • Great Neck, New York, United States, 11021
        • North Shore Long Island Jewish Medical Group, 600 Northern Boulevard, Suite 111
      • Great Neck, New York, United States, 11021
        • NYU Langone Long Island , 1000 Northern Boulevard, Suite 160
      • New York, New York, United States, 10016
        • Manhattan Medical Research Practice PLLC, 215 Lexington Avenue, 21st Floor
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • University of North Carolina Center for inflammatory Bowel Diseases, CB 7080, 130 Mason Farm Road, 4151 Bioinformatics Bldg.
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • Ohio GI and Liver Institute, 2925 Vernon Place 100
      • Cincinnati, Ohio, United States, 45249
        • Ohio GI and Liver Institute
    • Tennessee
      • Chattanooga, Tennessee, United States, 37421
        • ClinSearch, 6035 Shallowford Road, Suite 109
    • Texas
      • Fort Sam Houston, Texas, United States, 78284
        • Brooke Army Medical Center, 3551 Roger Brooke Drive
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine, 7200 Cambridge Street Suite 180.184, 10th Floor
      • Houston, Texas, United States, 77030
        • University of Texas Health Sciences Center at Houston, 6431 Fannin Street, Medical School Bldg 4-234
      • Humble, Texas, United States, 77036
        • Spring Gastroenterology Associates, 8901 FM 1960 West
      • Richardson, Texas, United States, 75082
        • DHAT Research Institute / Digestive Health Associates of Texas 3600 Shire Blvd, Suite 106
      • San Antonio, Texas, United States, 78215
        • Digestive Disease Center, 621 Camden Street, Suite 202
      • Tyler, Texas, United States, 75701
        • Tyler Research Institute, 1720 S. Beckham
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Gasteroenterology Associates of Northern Virgina, 3028 Javier Road
      • Richmond, Virginia, United States, 23249
        • McGuire DVAMC, 1201 Broad Rock Boulevard

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

  1. Signed fully informed consent provided as per this protocol.
  2. Diagnosis of Crohn's Disease confirmed by endoscopy or radiography and/or histology at least 6 months prior to randomization into the study.
  3. CD involving the ileum and/or colon
  4. Moderately to severely active CD (Crohn's Disease Activity Index (CDAI) score of greater than or equal to 220 and less than or equal to 450) at baseline.
  5. Current treatment with at least one of the following therapies:

    A. Oral 5-acetyl salicylic acid (5-ASA) compounds. Dose must be stable for at least 4 weeks before baseline.

    B. Corticosteroid therapy. Dose must be stable for at least 2 weeks before baseline.

    C. Azathioprine or 6-mercaptopurine (6-MP) or methotrexate. Dose must be stable for at least 8 weeks before baseline.

    D. Infliximab or adalimumab. Dose must be stable for at least 14 weeks before baseline.

  6. White blood cell count greater than or equal to 3.5 x 109 at screening.
  7. Active Crohn's disease, defined by at least one of the following: C-reactive protein greater than Upper Limit of Normal (ULN) at screening, fecal calprotectin greater than Upper Limit of Normal (ULN) at screening, OR radiographic (MRE or CTE) or endoscopic confirmation of the presence of active CD within 5 weeks of screening visit. .
  8. Subject agrees to use barrier contraceptive methods (i.e. diaphragm, cervical cap, contraceptive sponge or condom) with spermicidal foam/gel/cream/suppository, IUD/IUS or progestogen injection (Depo-Provera®) throughout the study and for at least 6 weeks after last study drug administration, unless subject is post-menopausal or otherwise incapable of becoming pregnant by reason of surgery or tubal ligation, or has had a vasectomy. In regions where local regulatory contraceptive requirements differ, the ICF will reflect local policies.

Exclusion Criteria

  1. Crohn's Disease involvement isolated to the mouth, upper gastrointestinal tract, or anus.
  2. History of total colectomy with ileorectal anastomosis or a proctocolectomy.
  3. Presence of active fistulizing Crohn's Disease or healed fistula within 2 months prior to screening.
  4. Subject has postoperative stoma, ostomy, or ileoanal pouch.
  5. Subject has short bowel syndrome.
  6. Subject is scheduled for surgical bowel resection.
  7. Subject has known symptomatic obstructive strictures or bowel perforation in the 6 months prior to screening.
  8. Change in dose or discontinuation of oral 5-acetyl salicylic acid (5-ASA) compounds less than 4 weeks prior to baseline.
  9. Change in dose or discontinuation of corticosteroids less than 2 weeks prior to baseline.
  10. Change in dose or discontinuation of azathioprine, 6-mercaptopurine (6-MP) or methotrexate less than 8 weeks prior to baseline.
  11. Change in dose or discontinuation of infliximab or adalimumab less than 14 weeks prior to baseline.
  12. Treatment with vedolizumab less than 120 days prior to baseline or biological therapies (apart from infliximab or adalimumab) less than 60 days prior to baseline.
  13. Previous treatment with rifabutin and/or clofazimine.
  14. Oral or parenteral antibiotics in the 4 weeks prior to baseline (topical antibiotics are permitted).
  15. Treatment with probiotics (excluding yogurt and yogurt-derived products) in the 4 weeks prior to baseline.
  16. Females who have a positive pregnancy test or are lactating.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: RHB-104
5 RHB-104 capsules administered orally BID
95 mg clarithromycin, 45 mg rifabutin, and 10 mg clofazimine
Placebo Comparator: Placebo
5 placebo capsules administered orally BID
5 placebo capsules administered orally BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Remission at Week 26
Time Frame: Week 26
Reduction of the total Crohn's Disease Activity Index (CDAI) score to less than 150. Lower CDAI scores indicate a better outcome.
Week 26

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response at Week 26
Time Frame: Week 26
Reduction of Crohn's Disease Activity Index (CDAI) score by a minimum of 100 points. Lower CDAI scores indicate a better outcome.
Week 26
Remission at Week 52
Time Frame: Week 52
Reduction of the total Crohn's Disease Activity Index (CDAI) score to less than 150. Lower CDAI scores indicate a better outcome.
Week 52
Durable Remission Week 26 Through Week 52
Time Frame: Week 26 through week 52
When a subject is in remission with a maximum CDAI score of 149 at every visit from Week 26 through and including Week 52
Week 26 through week 52
Remission at Week 16
Time Frame: Week 16
Reduction of the total Crohn's Disease Activity Index (CDAI) score to less than 150. Lower CDAI scores indicate a better outcome.
Week 16
Steroid Free Remission at Week 52
Time Frame: Week 52
Subjects who are maintained off steroids for a minimum of 3 weeks
Week 52

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of Remission
Time Frame: Baseline through week 52
Number of weeks that a subject is in a state of remission. Subjects who experienced remission and continued to be in remission at the time of their last CDAI assessment are censored at the date of their last CDAI assessment.
Baseline through week 52
Duration of Response
Time Frame: Baseline through week 52
Number of weeks a subject is in a state of response. Subjects who experienced response and continued to be in response at the time of their last CDAI assessment are censored at the date of their last CDAI assessment.
Baseline through week 52
Time to Remission
Time Frame: Baseline through week 52
[Date of first observed remission (CDAI score < 150) - Date of first dose or date of randomization if not dosed + 1] / 7 Days. Subjects who never experienced remission during the study are censored at the date of their last CDAI assessment.
Baseline through week 52
Time to Response
Time Frame: Baseline through week 52
[Date of first observed response (a reduction from baseline of ≥ 100 in CDAI score) - Date of first dose or date of randomization if not dosed + 1] / 7 Days. Subjects who never experienced response during the study are censored at the date of their last CDAI assessment.
Baseline through week 52
Durable Remission Week 16 Through Week 52
Time Frame: Week 16 through week 52
Remission in a subject from week 16 through week 52.
Week 16 through week 52
Response at Week 16
Time Frame: Week 16
Reduction of Crohn's Disease Activity Index (CDAI) score by a minimum of 100 points. Lower CDAI scores indicate a better outcome.
Week 16
Cardiac Safety
Time Frame: Week 26
Change-from-baseline to week 26 in QTcF (based on cardiac safety report)
Week 26
Cardiac Safety
Time Frame: Baseline through week 52
Placebo-corrected change-from-baseline to week 52 in QTcF (based on cardiac safety report)
Baseline through week 52

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: David Y. Graham, MD, Department of Medicine/Gastroenterology, Baylor College of Medicine, Houston

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2013

Primary Completion (Actual)

May 1, 2018

Study Completion (Actual)

August 1, 2019

Study Registration Dates

First Submitted

September 19, 2013

First Submitted That Met QC Criteria

September 23, 2013

First Posted (Estimate)

September 26, 2013

Study Record Updates

Last Update Posted (Actual)

December 8, 2020

Last Update Submitted That Met QC Criteria

November 29, 2020

Last Verified

June 1, 2020

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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