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

• ClinicalTrials.gov Identifier: NCT01951326
• Recruitment Status: Completed
• First Posted: September 26, 2013
• Results First Posted: May 1, 2020
• Last Update Posted: December 8, 2020
• Sponsor: RedHill Biopharma Limited
• Information provided by (Responsible Party): RedHill Biopharma Limited

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Crohn's Disease	Drug: RHB-104; Drug: Placebo	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 331 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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 Start Date: September 2013
• Actual Primary Completion Date: May 2018
• Actual Study Completion Date: August 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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.
2. 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.
3. 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
4. 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.
5. Steroid Free Remission at Week 52 [ Time Frame: Week 52 ]
   Subjects who are maintained off steroids for a minimum of 3 weeks

Other Outcome Measures:

1. 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.
2. 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.
3. 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.
4. 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.
5. Durable Remission Week 16 Through Week 52 [ Time Frame: Week 16 through week 52 ]
   Remission in a subject from week 16 through week 52.
6. 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.
7. Cardiac Safety [ Time Frame: Week 26 ]
   Change-from-baseline to week 26 in QTcF (based on cardiac safety report)
8. Cardiac Safety [ Time Frame: Baseline through week 52 ]
   Placebo-corrected change-from-baseline to week 52 in QTcF (based on cardiac safety report)

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Arizona

Del Sol Research Management, 850 N Knob Road

Tucson, Arizona, United States, 85710

United States, California

Associated Gastroenterology Medical Group, 1211 W. La Palmak Ave, Suite 303

Anaheim, California, United States, 92801

Medvin Clinical Research, 15627 Imperial Highway,

La Mirada, California, United States, 90638

Digestive Care Associates, Inc., 1000 Laurel St.

San Carlos, California, United States, 94070

Ventura Clinical Trials, 1835 Knoll Drive

Ventura, California, United States, 93003

United States, Connecticut

Medical Research Center of Connecticut, LLC

Hamden, Connecticut, United States, 06518

United States, Florida

Innovative Medical Research of South Florida, 2999 NE 191 St., Suite 330

Aventura, Florida, United States, 33180

Clinical Research of West Florida

Clearwater, Florida, United States, 33765

Sunrise Medical Research, Inc. 4700 N. State Road Building A, Suite 111

Lauderdale Lakes, Florida, United States, 33319

Gastroenterology Group of Naples, 1064 Goodlette Road

Naples, Florida, United States, 34102

Advanced Research Institute Inc., 7114 Congress Street

New Port Richey, Florida, United States, 34653

Endoscopic Research, Inc., 1817 North Mills Avenue

Orlando, Florida, United States, 32802

Advanced Medical Research Center, 1690 Dunlawton Ave., Suite 110

Port Orange, Florida, United States, 32127

United States, Georgia

Atlanta Center for Gastroenterology 2665 North Decatur Road Suite 550

Decatur, Georgia, United States, 30033

Gastrointestinal Specialists of Georgia PC, 711 Canton Rd. Suite 300

Marietta, Georgia, United States, 30060

United States, Illinois

Rush University Medical Center

Chicago, Illinois, United States, 60612

The Carle Foundation, 611 West Park Street

Urbana, Illinois, United States, 61801

United States, Kansas

Cotton-O'Neil Clinical Research Center, 720 SW Lane St.

Topeka, Kansas, United States, 66606

United States, Maryland

Investigative Clinical Research, 612 Ridgely Avenue, Suite 401,

Annapolis, Maryland, United States, 21401

Chevy Chase Clinical Research, 5550 Friendship Blvd.

Chevy Chase, Maryland, United States, 20815

United States, Massachusetts

Commonwealth Clinical Studies, 189 Quincy St.

Brockton, Massachusetts, United States, 02302-2926

United States, Michigan

Center For Digestive Health

Troy, Michigan, United States, 48098

West Michigan Clinical Research Center, 2093 Health Dr. SW, Suite 201

Wyoming, Michigan, United States, 49519

United States, Missouri

Ehrhardt Clinical Research, LLC, 108 Congress Street

Belton, Missouri, United States, 64012

United States, New Jersey

AGA Clinical Research Associates, Inc., 3205 Fire Road

Egg Harbor Township, New Jersey, United States, 08324

Holy Name Medical Center, 718 Teaneck Road

Teaneck, New Jersey, United States, 07666

United States, New York

Montefiore Medical Center, 111 East 210th Street

Bronx, New York, United States, 10467

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

Great Neck, New York, United States, 11021

Manhattan Medical Research Practice PLLC, 215 Lexington Avenue, 21st Floor

New York, New York, United States, 10016

United States, North Carolina

University of North Carolina Center for inflammatory Bowel Diseases, CB 7080, 130 Mason Farm Road, 4151 Bioinformatics Bldg.

Chapel Hill, North Carolina, United States, 27599

United States, Ohio

Ohio GI and Liver Institute, 2925 Vernon Place 100

Cincinnati, Ohio, United States, 45219

Ohio GI and Liver Institute

Cincinnati, Ohio, United States, 45249

United States, Tennessee

ClinSearch, 6035 Shallowford Road, Suite 109

Chattanooga, Tennessee, United States, 37421

United States, Texas

Brooke Army Medical Center, 3551 Roger Brooke Drive

Fort Sam Houston, Texas, United States, 78284

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

Houston, Texas, United States, 77030

Spring Gastroenterology Associates, 8901 FM 1960 West

Humble, Texas, United States, 77036

DHAT Research Institute / Digestive Health Associates of Texas 3600 Shire Blvd, Suite 106

Richardson, Texas, United States, 75082

Digestive Disease Center, 621 Camden Street, Suite 202

San Antonio, Texas, United States, 78215

Tyler Research Institute, 1720 S. Beckham

Tyler, Texas, United States, 75701

United States, Virginia

Gasteroenterology Associates of Northern Virgina, 3028 Javier Road

Fairfax, Virginia, United States, 22031

McGuire DVAMC, 1201 Broad Rock Boulevard

Richmond, Virginia, United States, 23249

Australia, New South Wales

Bankstown Hospital, Level 3, Department of Gastroenterology, Eldridge Road

Bankstown, New South Wales, Australia, 2200

Department of Gastroenterology and Hepatology, Concord Hospital, Hospital Road

Concord, New South Wales, Australia, 2139

Nepean Hospital, Derby Street

Kingswood, New South Wales, Australia, 2747

Department of Gastroenterology, Level 1, Clinic 123, New Clinical Building, Liverpool Hospital, Elizabeth St.

Liverpool, New South Wales, Australia, 2170

Australia, Queensland

Department of Gastroenterology and Hepatology, Level 9, Ned Hanlon Building, Royal Brisbane and Women's Hospital Corner Butterfield Street and Bowen Bridge Street

Herston, Queensland, Australia, 4029

Mater Hospital Brisbane, Department of Gastroenterology, Raymond Terrace

South Brisbane, Queensland, Australia, 4101

Australia, Victoria

Ballarat Health Services, Drummond St North

Ballarat, Victoria, Australia, 3350

Department of Gastroenterology, Eastern Health, ECRU, Level 2, 5 Arnold Street

Box Hill, Victoria, Australia, 3128

Department of Gastroenterology and Hepatology, Cabrini Medical Centre, 183 Wattletree Road

Malvern, Victoria, Australia, 3144

Bulgaria

MHAT "Sv. Karidad" EAD, Department of Internal Medicine / Gastroenterology, endocrinology and metabolic disorders, 23А, Nikola Vaptsarov Blvd

Plovdiv, Bulgaria, 4002

MHAT "Hadzhi Dimitar" OOD, Department of Internal Medicine / Gastroenterology and Endocrinology, 5, Dimitar Pehlivanov str.

Sliven, Bulgaria, 8800

UMHAT "Sv. Ivan Rilski" EAD; Clinic of Gastroenterology, 15, Akad. Ivan Geshov Blvd.,

Sofia, Bulgaria, 1432

ACIBADEM CITY CLINIC UNIVERSITY HOSPITAL EOOD, Oncology Center, Clinic of Gastroenterology, 66 A, Tsarigradsko shosse Blvd

Sofia, Bulgaria, 1784

DCC "Mladost-M Varna" OOD, office 528 V, 15, Republika Blvd.

Varna, Bulgaria, 9020

Canada, British Columbia

Discovery Clinical Services Ltd. 601 A Discovery St.

Victoria, British Columbia, Canada, V8T 5G4

Canada, Ontario

Mount Sinai Hospital, 600 University Avenue, Suite 445

Toronto, Ontario, Canada, M5G 1X5

Canada, Quebec

Montreal General Hospital Digestive Lab Research Institute McGill University Health Center, 1650 Cedar Avenue C10.145

Montreal, Quebec, Canada, H3G 1A4

Canada, Saskatchewan

University of Saskatchewan Royal University Hospital, 103 Hospital Drive IBD Clinical Trials Unit Rm 2658

Saskatoon, Saskatchewan, Canada, S7N 0W8

Czechia

Nemocnice Horovice, NH Hospital, a.s., Chirurgicke oddeleni, K Nemocnici 1106

Horovice, Czechia, 268 31

Gastroenterologie s.r.o., Manesova 646,

Hradec Kralove, Czechia, 500 02

HEPATO-GASTROENTEROLOGIE HK, s.r.o., Trida Edvarda Benese 1549/34

Hradec Kralove, Czechia, 50012

EGK s.r.o., Sanatorium sv. Anny, Gastroenterologicke oddeleni, Lucni 7a/2776,

Praha 3, Czechia, 13000

IBD centrum / ISCARE IVF a.s., Jankovcova 1569/2c

Praha, Czechia, 17000

ARTROSCAN, s.r.o., Gastroenterologicka ambulance, 5114 Trebovicka, Ostrava

Trebovice, Czechia, 722 00

Krajska zdravotni, a.s., Masarykova nemocnice o.z. Gastroenterologie, Socialni pece 3316/12A

Usti nad Labem, Czechia, 401 13

Israel

Assaf HaRofeh Medical Center, Gastroenterology Department, Harofeh Medical Center

Be'er Ya'aqov, Israel, 70300

Bnaizion Medical Center, Golomb 47

Haifa, Israel, 31048

The E. Wolfson Medical Center, 62 Halohamim Str.

Holon, Israel, 58100

Shaare Zedek Medical Center, Beith Street

Jerusalem, Israel, 91031

Ein Karem Medical Center, Kiryat Hadassah

Jerusalem, Israel, 91120

Meir, 59 Tchemacovsky St

Kfar-Saba, Israel, 44281

Galilee Medical Center, P.O.B. 21

Nahariya, Israel, 1210001

Holy Family Hospital, Namsawi St. POB 8

Nazareth, Israel, 16100

RMC Beilinson Hospital, 39 Jabotinsky Street

Petach-Tikva, Israel, 49100

Sourasky Medical Center, 6 Weizman Street

Tel Aviv, Israel, 64239

New Zealand

Shakespeare Specialist Group, North Shore, Suite 3, 181 Shakespeare Road, Milford Takapuna

Auckland, New Zealand, 0620

Christchurch Hospital

Christchurch, New Zealand, 4710

Gastroenterology Unit, Southern District Health Board, 201 Great King Street,

Dunedin, New Zealand, 9054

Department of Gastroenterology,Waikato Hospital

Hamilton, New Zealand, 3240

Clinical Trials Unit, Tauranga Hospital,

Tauranga, New Zealand, 3112

Poland

NZOZ Specjalistyczne Centrum Gastrologii GASTROMED Wiejska 81

Bialystok, Poland, 15-351

SP ZOZ MSWiA w Gdańsku, Oddział Gastroenterologiczny, ul. Kartuska 4/6

Gdańsk, Poland, 80-104

UNICARDIA Specjalistyczne Centrum Leczenia Chorob Serca i Naczyn & UNIMEDICA Specjalistyczne Centrum Medyczne Sp. z o.o. Kluczborska 15

Krakow, Poland, 31-271

Wojewodzki Szpital Kliniczny w Olsztynie Oddzial Gastroenterologiczny Żołnierska 18

Olsztyn, Poland, 10-561

ENDOSKOPIA sp. z o.o. B. Chrobrego 6/8

Sopot, Poland, 81-756

EuroMedis sp. z.o.o., ul. Powstanców Wielkopolskich 33a

Szczecin, Poland, 70-111

"GASTROMED" Kopon, Zmudzinski i wspolnicy sp. j., Specjalistyczne Centrum Gastroskopii i Endoskopii, Specjalistyczne Gabinety Lekarskie Grudziadzka 11

Torun, Poland, 87-100

Centralny Szpital Kliniczny MSW w Warszawie Klinika Chorob Wewnetrznych i Gastroenterologii Woloska 137

Warszawa, Poland, 02-507

ARS MEDICA s.c. Rybak Maria, Rybak Zbigniew, Powstancow Slaskich 56A/2

Wroclaw, Poland, 53-333

Centrum Medyczne Szpital Sw. Rodziny Sp. z o.o. Wigury 19

Łódź, Poland, 90-302

Serbia

: 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, 11000

Department of Gastroenterology and Hepatology, Clinical Hospital Center Zemun Vukova 9

Belgrade, Serbia, 11080

: Center for Gastroenterohepatology, Clinic for Internal Medicine, Clinical Center of Kragujevac Zmaj Jovina 30

Kragujevac, Serbia, 34000

: Clinic of Gastroenterology and Hepatology, Clinical Center of Vojvodina Hajduk Veljkova 1

Novi Sad, Serbia, 21000

Slovakia

Univerzitna nemocnica Bratislava - Nemocnica Ružinov, V. Interná klinika LFUK a UNB, Gastroenterologické a hepatologické oddelenie, Ruzinovska 6

Bratislava, Slovakia, 82606

Univerzitná nemocnica Bratislava - Nemocnica sv. Cyrila a Metoda Gastroenterologická klinika SZU a UNB Antolská 11

Bratislava, Slovakia, 851 07

Breznianske centrum gastroenterologie, s.r.o. Banisko 1

Brezno, Slovakia, 97701

PIGEAS s.r.Prieložtek 1, o.,

Martin, Slovakia, 036 01

KM Management spol. s.r.o., Gastroenterologické a hepatologické centrum Nitra, Špitálska 13

Nitra, Slovakia, 949 01

Sponsors and Collaborators

RedHill Biopharma Limited

Investigators

• Study Director: Ira N Kalfus, MD; RedHill Biopharma
• Principal Investigator: David Y. Graham, MD; Department of Medicine/Gastroenterology, Baylor College of Medicine, Houston

  Study Documents (Full-Text)

Documents provided by RedHill Biopharma Limited:

Statistical Analysis Plan  [PDF] April 5, 2018

Study Protocol  [PDF] September 29, 2017

More Information

Additional Information:

Related Info 

• Responsible Party: RedHill Biopharma Limited
• ClinicalTrials.gov Identifier: NCT01951326
• Other Study ID Numbers: RHB-104-01
• First Posted: September 26, 2013
• Results First Posted: May 1, 2020
• Last Update Posted: December 8, 2020
• Last Verified: June 2020

Keywords provided by RedHill Biopharma Limited:

Crohn's Disease; moderate to severe; remission; MAP; antibiotic

Additional relevant MeSH terms:

Crohn Disease; Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases