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

NCT01951326 | Completed Phase 3 Results DMC

• 1 other identifier: RHB-104-01
• Study Type: interventional
• Target: 331
• Locations: 10 countries
• Sites: 103

Brief Summary

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

Conditions

Crohn's Disease

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Response at Week 26

  Week 26

• Remission at Week 52

  Week 52

• Durable Remission Week 26 Through Week 52

  Week 26 through week 52

• Remission at Week 16

  Week 16

• Steroid Free Remission at Week 52

  Week 52

Other Outcomes (8)

• Duration of Remission

  Baseline through week 52

• Duration of Response

  Baseline through week 52

• Time to Remission

  Baseline through week 52

Study Arms (2)

RHB-104

ACTIVE COMPARATOR

5 RHB-104 capsules administered orally BID

Drug: RHB-104

Placebo

PLACEBO COMPARATOR

5 placebo capsules administered orally BID

Drug: Placebo

Interventions

RHB-104 DRUG

95 mg clarithromycin, 45 mg rifabutin, and 10 mg clofazimine

RHB-104

Placebo DRUG

5 placebo capsules administered orally BID

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed fully informed consent provided as per this protocol.
• Diagnosis of Crohn's Disease confirmed by endoscopy or radiography and/or histology at least 6 months prior to randomization into the study.
• CD involving the ileum and/or colon
• 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.
• 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.
• White blood cell count greater than or equal to 3.5 x 109 at screening.
• 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. .
• 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.

You may not qualify if:

• Crohn's Disease involvement isolated to the mouth, upper gastrointestinal tract, or anus.
• History of total colectomy with ileorectal anastomosis or a proctocolectomy.
• Presence of active fistulizing Crohn's Disease or healed fistula within 2 months prior to screening.
• Subject has postoperative stoma, ostomy, or ileoanal pouch.
• Subject has short bowel syndrome.
• Subject is scheduled for surgical bowel resection.
• Subject has known symptomatic obstructive strictures or bowel perforation in the 6 months prior to screening.
• Change in dose or discontinuation of oral 5-acetyl salicylic acid (5-ASA) compounds less than 4 weeks prior to baseline.
• Change in dose or discontinuation of corticosteroids less than 2 weeks prior to baseline.
• Change in dose or discontinuation of azathioprine, 6-mercaptopurine (6-MP) or methotrexate less than 8 weeks prior to baseline.
• Change in dose or discontinuation of infliximab or adalimumab less than 14 weeks prior to baseline.
• 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.
• Previous treatment with rifabutin and/or clofazimine.
• Oral or parenteral antibiotics in the 4 weeks prior to baseline (topical antibiotics are permitted).
• Treatment with probiotics (excluding yogurt and yogurt-derived products) in the 4 weeks prior to baseline.

Sponsors & Collaborators

• RedHill Biopharma Limited: lead

Study Sites (103)

Del Sol Research Management, 850 N Knob Road

Tucson, Arizona, 85710, United States

Location

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

Anaheim, California, 92801, United States

Location

Medvin Clinical Research, 15627 Imperial Highway,

La Mirada, California, 90638, United States

Location

Digestive Care Associates, Inc., 1000 Laurel St.

San Carlos, California, 94070, United States

Location

Ventura Clinical Trials, 1835 Knoll Drive

Ventura, California, 93003, United States

Location

Medical Research Center of Connecticut, LLC

Hamden, Connecticut, 06518, United States

Location

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

Aventura, Florida, 33180, United States

Location

Clinical Research of West Florida

Clearwater, Florida, 33765, United States

Location

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

Lauderdale Lakes, Florida, 33319, United States

Location

Gastroenterology Group of Naples, 1064 Goodlette Road

Naples, Florida, 34102, United States

Location

Advanced Research Institute Inc., 7114 Congress Street

New Port Richey, Florida, 34653, United States

Location

Endoscopic Research, Inc., 1817 North Mills Avenue

Orlando, Florida, 32802, United States

Location

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

Port Orange, Florida, 32127, United States

Location

Atlanta Center for Gastroenterology 2665 North Decatur Road Suite 550

Decatur, Georgia, 30033, United States

Location

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

Marietta, Georgia, 30060, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

The Carle Foundation, 611 West Park Street

Urbana, Illinois, 61801, United States

Location

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

Topeka, Kansas, 66606, United States

Location

Investigative Clinical Research, 612 Ridgely Avenue, Suite 401,

Annapolis, Maryland, 21401, United States

Location

Chevy Chase Clinical Research, 5550 Friendship Blvd.

Chevy Chase, Maryland, 20815, United States

Location

Commonwealth Clinical Studies, 189 Quincy St.

Brockton, Massachusetts, 02302-2926, United States

Location

Center For Digestive Health

Troy, Michigan, 48098, United States

Location

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

Wyoming, Michigan, 49519, United States

Location

Ehrhardt Clinical Research, LLC, 108 Congress Street

Belton, Missouri, 64012, United States

Location

AGA Clinical Research Associates, Inc., 3205 Fire Road

Egg Harbor, New Jersey, 08324, United States

Location

Holy Name Medical Center, 718 Teaneck Road

Teaneck, New Jersey, 07666, United States

Location

North Shore Long Island Jewish Medical Group, 600 Northern Boulevard, Suite 111

Great Neck, New York, 11021, United States

Location

NYU Langone Long Island , 1000 Northern Boulevard, Suite 160

Great Neck, New York, 11021, United States

Location

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

New York, New York, 10016, United States

Location

Montefiore Medical Center, 111 East 210th Street

The Bronx, New York, 10467, United States

Location

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

Chapel Hill, North Carolina, 27599, United States

Location

Ohio GI and Liver Institute, 2925 Vernon Place 100

Cincinnati, Ohio, 45219, United States

Location

Ohio GI and Liver Institute

Cincinnati, Ohio, 45249, United States

Location

ClinSearch, 6035 Shallowford Road, Suite 109

Chattanooga, Tennessee, 37421, United States

Location

Brooke Army Medical Center, 3551 Roger Brooke Drive

Fort Sam Houston, Texas, 78284, United States

Location

Baylor College of Medicine, 7200 Cambridge Street Suite 180.184, 10th Floor

Houston, Texas, 77030, United States

Location

University of Texas Health Sciences Center at Houston, 6431 Fannin Street, Medical School Bldg 4-234

Houston, Texas, 77030, United States

Location

Spring Gastroenterology Associates, 8901 FM 1960 West

Humble, Texas, 77036, United States

Location

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

Richardson, Texas, 75082, United States

Location

Digestive Disease Center, 621 Camden Street, Suite 202

San Antonio, Texas, 78215, United States

Location

Tyler Research Institute, 1720 S. Beckham

Tyler, Texas, 75701, United States

Location

Gasteroenterology Associates of Northern Virgina, 3028 Javier Road

Fairfax, Virginia, 22031, United States

Location

McGuire DVAMC, 1201 Broad Rock Boulevard

Richmond, Virginia, 23249, United States

Location

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

Bankstown, New South Wales, 2200, Australia

Location

Department of Gastroenterology and Hepatology, Concord Hospital, Hospital Road

Concord, New South Wales, 2139, Australia

Location

Nepean Hospital, Derby Street

Kingswood, New South Wales, 2747, Australia

Location

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

Liverpool, New South Wales, 2170, Australia

Location

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, 4029, Australia

Location

Mater Hospital Brisbane, Department of Gastroenterology, Raymond Terrace

South Brisbane, Queensland, 4101, Australia

Location

Ballarat Health Services, Drummond St North

Ballarat, Victoria, 3350, Australia

Location

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

Box Hill, Victoria, 3128, Australia

Location

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

Malvern, Victoria, 3144, Australia

Location

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

Plovdiv, 4002, Bulgaria

Location

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

Sliven, 8800, Bulgaria

Location

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

Sofia, 1432, Bulgaria

Location

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

Sofia, 1784, Bulgaria

Location

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

Varna, 9020, Bulgaria

Location

Discovery Clinical Services Ltd. 601 A Discovery St.

Victoria, British Columbia, V8T 5G4, Canada

Location

Mount Sinai Hospital, 600 University Avenue, Suite 445

Toronto, Ontario, M5G 1X5, Canada

Location

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

Montreal, Quebec, H3G 1A4, Canada

Location

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

Saskatoon, Saskatchewan, S7N 0W8, Canada

Location

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

Hořovice, 268 31, Czechia

Location

Gastroenterologie s.r.o., Manesova 646,

Hradec Králové, 500 02, Czechia

Location

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

Hradec Králové, 50012, Czechia

Location

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

Prague, 13000, Czechia

Location

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

Prague, 17000, Czechia

Location

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

Třebovice, 722 00, Czechia

Location

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

Ústí nad Labem, 401 13, Czechia

Location

Assaf HaRofeh Medical Center, Gastroenterology Department, Harofeh Medical Center

Be’er Ya‘aqov, 70300, Israel

Location

Bnaizion Medical Center, Golomb 47

Haifa, 31048, Israel

Location

The E. Wolfson Medical Center, 62 Halohamim Str.

Holon, 58100, Israel

Location

Shaare Zedek Medical Center, Beith Street

Jerusalem, 91031, Israel

Location

Ein Karem Medical Center, Kiryat Hadassah

Jerusalem, 91120, Israel

Location

Meir, 59 Tchemacovsky St

Kfar Saba, 44281, Israel

Location

Galilee Medical Center, P.O.B. 21

Nahariya, 1210001, Israel

Location

Holy Family Hospital, Namsawi St. POB 8

Nazareth, 16100, Israel

Location

RMC Beilinson Hospital, 39 Jabotinsky Street

Petah Tikva, 49100, Israel

Location

Sourasky Medical Center, 6 Weizman Street

Tel Aviv, 64239, Israel

Location

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

Auckland, 0620, New Zealand

Location

Christchurch Hospital

Christchurch, 4710, New Zealand

Location

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

Dunedin, 9054, New Zealand

Location

Department of Gastroenterology,Waikato Hospital

Hamilton, 3240, New Zealand

Location

Clinical Trials Unit, Tauranga Hospital,

Tauranga, 3112, New Zealand

Location

NZOZ Specjalistyczne Centrum Gastrologii GASTROMED Wiejska 81

Bialystok, 15-351, Poland

Location

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

Gdansk, 80-104, Poland

Location

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

Krakow, 31-271, Poland

Location

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

Lodz, 90-302, Poland

Location

Wojewodzki Szpital Kliniczny w Olsztynie Oddzial Gastroenterologiczny Żołnierska 18

Olsztyn, 10-561, Poland

Location

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

Sopot, 81-756, Poland

Location

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

Szczecin, 70-111, Poland

Location

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

Torun, 87-100, Poland

Location

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

Warsaw, 02-507, Poland

Location

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

Wroclaw, 53-333, Poland

Location

: Clinic for Gastroenterology and Hepatology, Clinical Center of Serbia Koste Todorovica 2

Belgrade, 11000, Serbia

Location

Clinical Department of Gastroenterology and Hepatology, Clinic for Internal Diseases, Clinical Hospital Center Zvezdara Dimitrija Tucovica 161

Belgrade, 11000, Serbia

Location

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

Belgrade, 11080, Serbia

Location

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

Kragujevac, 34000, Serbia

Location

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

Novi Sad, 21000, Serbia

Location

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

Bratislava, 82606, Slovakia

Location

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

Bratislava, 851 07, Slovakia

Location

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

Brezno, 97701, Slovakia

Location

PIGEAS s.r.Prieložtek 1, o.,

Martin, 036 01, Slovakia

Location

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

Nitra, 949 01, Slovakia

Location

Related Publications (1)

• Graham DY, Naser SA, Borody T, Hebzda Z, Sarles H, Levenson S, Hardi R, Arlukowicz T, Svorcan P, Fathi R, Bibliowicz A, Anderson P, McLean P, Fehrmann C, Harris MS, Zhao S, Kalfus IN. Randomized, Double-Blind, Placebo-Controlled Study of Anti-Mycobacterial Therapy (RHB-104) in Active Crohn's Disease. Antibiotics (Basel). 2024 Jul 25;13(8):694. doi: 10.3390/antibiotics13080694.

  PMID: 39199994 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Crohn Disease

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Reza Fathi, Senior VP Research and Development
• Organization: RedHill Biopharma

reza@redhillbio.com

972-(0)3-541-3131

Study Officials

• Ira N Kalfus, MD

  RedHill Biopharma

  STUDY DIRECTOR

• David Y. Graham, MD

  Department of Medicine/Gastroenterology, Baylor College of Medicine, Houston

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2013
• First Posted: September 26, 2013
• Study Start: September 1, 2013
• Primary Completion: May 1, 2018
• Study Completion: August 1, 2019
• Last Updated: December 8, 2020
• Results First Posted: May 1, 2020

Record last verified: 2020-06

Locations

BU (5); US (43); SL (5); IL (10); SE (5); PL (10); AU (9); CA (4); CZ (7); NZ (5)