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

Crohn's Disease Clinical Trial

— MAPUS  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01951326
• Other study ID #: RHB-104-01
• Status: Completed
• Phase: Phase 3
• Start date: September 2013
• Est. completion date: August 2019

Study information

• Verified date: June 2020
• Source: RedHill Biopharma Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 331
• Est. completion date: August 2019
• Est. primary completion date: May 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Crohn Disease
• Crohn's Disease

Intervention

Drug:
• RHB-104
95 mg clarithromycin, 45 mg rifabutin, and 10 mg clofazimine
• Placebo
5 placebo capsules administered orally BID

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
RedHill Biopharma Limited

Countries where clinical trial is conducted

United States,  Australia,  Bulgaria,  Canada,  Czechia,  Israel,  New Zealand,  Poland,  Serbia,  Slovakia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Duration of Remission	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
Other	Duration of Response	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
Other	Time to Remission	[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
Other	Time to Response	[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
Other	Durable Remission Week 16 Through Week 52	Remission in a subject from week 16 through week 52.	Week 16 through week 52
Other	Response at 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
Other	Cardiac Safety	Change-from-baseline to week 26 in QTcF (based on cardiac safety report)	Week 26
Other	Cardiac Safety	Placebo-corrected change-from-baseline to week 52 in QTcF (based on cardiac safety report)	Baseline through week 52
Primary	Remission at 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	Response at 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
Secondary	Remission at 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
Secondary	Durable Remission 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
Secondary	Remission at 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
Secondary	Steroid Free Remission at Week 52	Subjects who are maintained off steroids for a minimum of 3 weeks	Week 52

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