Clinical trial NCT01951326: Efficacy and Safety of Anti-MAP Therapy in Adult Crohn's Disease
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Crohn's Disease
Keywords: Crohn's Disease
moderate to severe
remission
MAP
antibiotic
Lead sponsor: RedHill Biopharma Limited
Sponsor class: INDUSTRY
First posted: 2013-09-26
Enrollment: 331
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility 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.

Primary outcomes:
measure: Remission at Week 26
timeFrame: Week 26
Secondary outcomes:
measure: Response at Week 26
timeFrame: Week 26
measure: Remission at Week 52
timeFrame: Week 52
measure: Durable Remission Week 26 Through Week 52
timeFrame: Week 26 through week 52
measure: Remission at Week 16
timeFrame: Week 16
measure: Steroid Free Remission at Week 52
timeFrame: Week 52
Other outcomes:
measure: Duration of Remission
timeFrame: Baseline through week 52
measure: Duration of Response
timeFrame: Baseline through week 52
measure: Time to Remission
timeFrame: Baseline through week 52
measure: Time to Response
timeFrame: Baseline through week 52
measure: Durable Remission Week 16 Through Week 52
timeFrame: Week 16 through week 52
measure: Response at Week 16
timeFrame: Week 16
measure: Cardiac Safety
timeFrame: Week 26
measure: Cardiac Safety
timeFrame: Baseline through week 52
Locations:
city: Tucson
country: United States
facility: Del Sol Research Management, 850 N Knob Road
state: Arizona
city: Anaheim
country: United States
facility: Associated Gastroenterology Medical Group, 1211 W. La Palmak Ave, Suite 303
state: California
city: La Mirada
country: United States
facility: Medvin Clinical Research, 15627 Imperial Highway,
state: California
city: San Carlos
country: United States
facility: Digestive Care Associates, Inc., 1000 Laurel St.
state: California
city: Ventura
country: United States
facility: Ventura Clinical Trials, 1835 Knoll Drive
state: California
city: Hamden
country: United States
facility: Medical Research Center of Connecticut, LLC
state: Connecticut
city: Aventura
country: United States
facility: Innovative Medical Research of South Florida, 2999 NE 191 St., Suite 330
state: Florida
city: Clearwater
country: United States
facility: Clinical Research of West Florida
state: Florida
city: Lauderdale Lakes
country: United States
facility: Sunrise Medical Research, Inc. 4700 N. State Road Building A, Suite 111
state: Florida
city: Naples
country: United States
facility: Gastroenterology Group of Naples, 1064 Goodlette Road
state: Florida
city: New Port Richey
country: United States
facility: Advanced Research Institute Inc., 7114 Congress Street
state: Florida
city: Orlando
country: United States
facility: Endoscopic Research, Inc., 1817 North Mills Avenue
state: Florida
city: Port Orange
country: United States
facility: Advanced Medical Research Center, 1690 Dunlawton Ave., Suite 110
state: Florida
city: Decatur
country: United States
facility: Atlanta Center for Gastroenterology 2665 North Decatur Road Suite 550
state: Georgia
city: Marietta
country: United States
facility: Gastrointestinal Specialists of Georgia PC, 711 Canton Rd. Suite 300
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Urbana
country: United States
facility: The Carle Foundation, 611 West Park Street
state: Illinois
city: Topeka
country: United States
facility: Cotton-O'Neil Clinical Research Center, 720 SW Lane St.
state: Kansas
city: Annapolis
country: United States
facility: Investigative Clinical Research, 612 Ridgely Avenue, Suite 401,
state: Maryland
city: Chevy Chase
country: United States
facility: Chevy Chase Clinical Research, 5550 Friendship Blvd.
state: Maryland
city: Brockton
country: United States
facility: Commonwealth Clinical Studies, 189 Quincy St.
state: Massachusetts
city: Troy
country: United States
facility: Center For Digestive Health
state: Michigan
city: Wyoming
country: United States
facility: West Michigan Clinical Research Center, 2093 Health Dr. SW, Suite 201
state: Michigan
city: Belton
country: United States
facility: Ehrhardt Clinical Research, LLC, 108 Congress Street
state: Missouri
city: Egg Harbor Township
country: United States
facility: AGA Clinical Research Associates, Inc., 3205 Fire Road
state: New Jersey
city: Teaneck
country: United States
facility: Holy Name Medical Center, 718 Teaneck Road
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center, 111 East 210th Street
state: New York
city: Great Neck
country: United States
facility: North Shore Long Island Jewish Medical Group, 600 Northern Boulevard, Suite 111
state: New York
city: Great Neck
country: United States
facility: NYU Langone Long Island , 1000 Northern Boulevard, Suite 160
state: New York
city: New York
country: United States
facility: Manhattan Medical Research Practice PLLC, 215 Lexington Avenue, 21st Floor
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina Center for inflammatory Bowel Diseases, CB 7080, 130 Mason Farm Road, 4151 Bioinformatics Bldg.
state: North Carolina
city: Cincinnati
country: United States
facility: Ohio GI and Liver Institute, 2925 Vernon Place 100
state: Ohio
city: Cincinnati
country: United States
facility: Ohio GI and Liver Institute
state: Ohio
city: Chattanooga
country: United States
facility: ClinSearch, 6035 Shallowford Road, Suite 109
state: Tennessee
city: Fort Sam Houston
country: United States
facility: Brooke Army Medical Center, 3551 Roger Brooke Drive
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine, 7200 Cambridge Street Suite 180.184, 10th Floor
state: Texas
city: Houston
country: United States
facility: University of Texas Health Sciences Center at Houston, 6431 Fannin Street, Medical School Bldg 4-234
state: Texas
city: Humble
country: United States
facility: Spring Gastroenterology Associates, 8901 FM 1960 West
state: Texas
city: Richardson
country: United States
facility: DHAT Research Institute / Digestive Health Associates of Texas 3600 Shire Blvd, Suite 106
state: Texas
city: San Antonio
country: United States
facility: Digestive Disease Center, 621 Camden Street, Suite 202
state: Texas
city: Tyler
country: United States
facility: Tyler Research Institute, 1720 S. Beckham
state: Texas
city: Fairfax
country: United States
facility: Gasteroenterology Associates of Northern Virgina, 3028 Javier Road
state: Virginia
city: Richmond
country: United States
facility: McGuire DVAMC, 1201 Broad Rock Boulevard
state: Virginia
city: Bankstown
country: Australia
facility: Bankstown Hospital, Level 3, Department of Gastroenterology, Eldridge Road
state: New South Wales
city: Concord
country: Australia
facility: Department of Gastroenterology and Hepatology, Concord Hospital, Hospital Road
state: New South Wales
city: Kingswood
country: Australia
facility: Nepean Hospital, Derby Street
state: New South Wales
city: Liverpool
country: Australia
facility: Department of Gastroenterology, Level 1, Clinic 123, New Clinical Building, Liverpool Hospital, Elizabeth St.
state: New South Wales
city: Herston
country: Australia
facility: Department of Gastroenterology and Hepatology, Level 9, Ned Hanlon Building, Royal Brisbane and Women's Hospital Corner Butterfield Street and Bowen Bridge Street
state: Queensland
city: South Brisbane
country: Australia
facility: Mater Hospital Brisbane, Department of Gastroenterology, Raymond Terrace
state: Queensland
city: Ballarat
country: Australia
facility: Ballarat Health Services, Drummond St North
state: Victoria
city: Box Hill
country: Australia
facility: Department of Gastroenterology, Eastern Health, ECRU, Level 2, 5 Arnold Street
state: Victoria
city: Malvern
country: Australia
facility: Department of Gastroenterology and Hepatology, Cabrini Medical Centre, 183 Wattletree Road
state: Victoria
city: Plovdiv
country: Bulgaria
facility: MHAT "Sv. Karidad" EAD, Department of Internal Medicine / Gastroenterology, endocrinology and metabolic disorders, 23А, Nikola Vaptsarov Blvd
city: Sliven
country: Bulgaria
facility: MHAT "Hadzhi Dimitar" OOD, Department of Internal Medicine / Gastroenterology and Endocrinology, 5, Dimitar Pehlivanov str.
city: Sofia
country: Bulgaria
facility: UMHAT "Sv. Ivan Rilski" EAD; Clinic of Gastroenterology, 15, Akad. Ivan Geshov Blvd.,
city: Sofia
country: Bulgaria
facility: ACIBADEM CITY CLINIC UNIVERSITY HOSPITAL EOOD, Oncology Center, Clinic of Gastroenterology, 66 A, Tsarigradsko shosse Blvd
city: Varna
country: Bulgaria
facility: DCC "Mladost-M Varna" OOD, office 528 V, 15, Republika Blvd.
city: Victoria
country: Canada
facility: Discovery Clinical Services Ltd. 601 A Discovery St.
state: British Columbia
city: Toronto
country: Canada
facility: Mount Sinai Hospital, 600 University Avenue, Suite 445
state: Ontario
city: Montreal
country: Canada
facility: Montreal General Hospital Digestive Lab Research Institute McGill University Health Center, 1650 Cedar Avenue C10.145
state: Quebec
city: Saskatoon
country: Canada
facility: University of Saskatchewan Royal University Hospital, 103 Hospital Drive IBD Clinical Trials Unit Rm 2658
state: Saskatchewan
city: Horovice
country: Czechia
facility: Nemocnice Horovice, NH Hospital, a.s., Chirurgicke oddeleni, K Nemocnici 1106
city: Hradec Kralove
country: Czechia
facility: Gastroenterologie s.r.o., Manesova 646,
city: Hradec Kralove
country: Czechia
facility: HEPATO-GASTROENTEROLOGIE HK, s.r.o., Trida Edvarda Benese 1549/34
city: Praha 3
country: Czechia
facility: EGK s.r.o., Sanatorium sv. Anny, Gastroenterologicke oddeleni, Lucni 7a/2776,
city: Praha
country: Czechia
facility: IBD centrum / ISCARE IVF a.s., Jankovcova 1569/2c
city: Trebovice
country: Czechia
facility: ARTROSCAN, s.r.o., Gastroenterologicka ambulance, 5114 Trebovicka, Ostrava
city: Usti nad Labem
country: Czechia
facility: Krajska zdravotni, a.s., Masarykova nemocnice o.z. Gastroenterologie, Socialni pece 3316/12A
city: Be'er Ya'aqov
country: Israel
facility: Assaf HaRofeh Medical Center, Gastroenterology Department, Harofeh Medical Center
city: Haifa
country: Israel
facility: Bnaizion Medical Center, Golomb 47
city: Holon
country: Israel
facility: The E. Wolfson Medical Center, 62 Halohamim Str.
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center, Beith Street
city: Jerusalem
country: Israel
facility: Ein Karem Medical Center, Kiryat Hadassah
city: Kfar-Saba
country: Israel
facility: Meir, 59 Tchemacovsky St
city: Nahariya
country: Israel
facility: Galilee Medical Center, P.O.B. 21
city: Nazareth
country: Israel
facility: Holy Family Hospital, Namsawi St. POB 8
city: Petach-Tikva
country: Israel
facility: RMC Beilinson Hospital, 39 Jabotinsky Street
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center, 6 Weizman Street
city: Auckland
country: New Zealand
facility: Shakespeare Specialist Group, North Shore, Suite 3, 181 Shakespeare Road, Milford Takapuna
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
city: Dunedin
country: New Zealand
facility: Gastroenterology Unit, Southern District Health Board, 201 Great King Street,
city: Hamilton
country: New Zealand
facility: Department of Gastroenterology,Waikato Hospital
city: Tauranga
country: New Zealand
facility: Clinical Trials Unit, Tauranga Hospital,
city: Bialystok
country: Poland
facility: NZOZ Specjalistyczne Centrum Gastrologii GASTROMED Wiejska 81
city: Gdańsk
country: Poland
facility: SP ZOZ MSWiA w Gdańsku, Oddział Gastroenterologiczny, ul. Kartuska 4/6
city: Krakow
country: Poland
facility: UNICARDIA Specjalistyczne Centrum Leczenia Chorob Serca i Naczyn & UNIMEDICA Specjalistyczne Centrum Medyczne Sp. z o.o. Kluczborska 15
city: Olsztyn
country: Poland
facility: Wojewodzki Szpital Kliniczny w Olsztynie Oddzial Gastroenterologiczny Żołnierska 18
city: Sopot
country: Poland
facility: ENDOSKOPIA sp. z o.o. B. Chrobrego 6/8
city: Szczecin
country: Poland
facility: EuroMedis sp. z.o.o., ul. Powstanców Wielkopolskich 33a
city: Torun
country: Poland
facility: "GASTROMED" Kopon, Zmudzinski i wspolnicy sp. j., Specjalistyczne Centrum Gastroskopii i Endoskopii, Specjalistyczne Gabinety Lekarskie Grudziadzka 11
city: Warszawa
country: Poland
facility: Centralny Szpital Kliniczny MSW w Warszawie Klinika Chorob Wewnetrznych i Gastroenterologii Woloska 137
city: Wroclaw
country: Poland
facility: ARS MEDICA s.c. Rybak Maria, Rybak Zbigniew, Powstancow Slaskich 56A/2
city: Łódź
country: Poland
facility: Centrum Medyczne Szpital Sw. Rodziny Sp. z o.o. Wigury 19
city: Belgrade
country: Serbia
facility: : Clinic for Gastroenterology and Hepatology, Clinical Center of Serbia Koste Todorovica 2
city: Belgrade
country: Serbia
facility: Clinical Department of Gastroenterology and Hepatology, Clinic for Internal Diseases, Clinical Hospital Center Zvezdara Dimitrija Tucovica 161
city: Belgrade
country: Serbia
facility: Department of Gastroenterology and Hepatology, Clinical Hospital Center Zemun Vukova 9
city: Kragujevac
country: Serbia
facility: : Center for Gastroenterohepatology, Clinic for Internal Medicine, Clinical Center of Kragujevac Zmaj Jovina 30
city: Novi Sad
country: Serbia
facility: : Clinic of Gastroenterology and Hepatology, Clinical Center of Vojvodina Hajduk Veljkova 1
city: Bratislava
country: Slovakia
facility: Univerzitna nemocnica Bratislava - Nemocnica Ružinov, V. Interná klinika LFUK a UNB, Gastroenterologické a hepatologické oddelenie, Ruzinovska 6
city: Bratislava
country: Slovakia
facility: Univerzitná nemocnica Bratislava - Nemocnica sv. Cyrila a Metoda Gastroenterologická klinika SZU a UNB Antolská 11
city: Brezno
country: Slovakia
facility: Breznianske centrum gastroenterologie, s.r.o. Banisko 1
city: Martin
country: Slovakia
facility: PIGEAS s.r.Prieložtek 1, o.,
city: Nitra
country: Slovakia
facility: KM Management spol. s.r.o., Gastroenterologické a hepatologické centrum Nitra, Špitálska 13
Study officials:
affiliation: RedHill Biopharma
name: Ira N Kalfus, MD
role: STUDY_DIRECTOR
affiliation: Department of Medicine/Gastroenterology, Baylor College of Medicine, Houston
name: David Y. Graham, MD
role: PRINCIPAL_INVESTIGATOR
References: