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

NCT ID: NCT01951326

Last Updated: 2020-12-08

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

331 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-09-30

Study Completion Date

2019-08-31

Brief Summary

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

Detailed Description

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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.

Conditions

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Crohn's Disease

Keywords

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Crohn's Disease moderate to severe remission MAP antibiotic

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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RHB-104

5 RHB-104 capsules administered orally BID

Group Type ACTIVE_COMPARATOR

RHB-104

Intervention Type DRUG

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

Placebo

5 placebo capsules administered orally BID

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

5 placebo capsules administered orally BID

Interventions

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RHB-104

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

Intervention Type DRUG

Placebo

5 placebo capsules administered orally BID

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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RedHill Biopharma Limited

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ira N Kalfus, MD

Role: STUDY_DIRECTOR

RedHill Biopharma

David Y. Graham, MD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

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Del Sol Research Management, 850 N Knob Road

Tucson, Arizona, United States

Site Status

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

Anaheim, California, United States

Site Status

Medvin Clinical Research, 15627 Imperial Highway,

La Mirada, California, United States

Site Status

Digestive Care Associates, Inc., 1000 Laurel St.

San Carlos, California, United States

Site Status

Ventura Clinical Trials, 1835 Knoll Drive

Ventura, California, United States

Site Status

Medical Research Center of Connecticut, LLC

Hamden, Connecticut, United States

Site Status

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

Aventura, Florida, United States

Site Status

Clinical Research of West Florida

Clearwater, Florida, United States

Site Status

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

Lauderdale Lakes, Florida, United States

Site Status

Gastroenterology Group of Naples, 1064 Goodlette Road

Naples, Florida, United States

Site Status

Advanced Research Institute Inc., 7114 Congress Street

New Port Richey, Florida, United States

Site Status

Endoscopic Research, Inc., 1817 North Mills Avenue

Orlando, Florida, United States

Site Status

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

Port Orange, Florida, United States

Site Status

Atlanta Center for Gastroenterology 2665 North Decatur Road Suite 550

Decatur, Georgia, United States

Site Status

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

Marietta, Georgia, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

The Carle Foundation, 611 West Park Street

Urbana, Illinois, United States

Site Status

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

Topeka, Kansas, United States

Site Status

Investigative Clinical Research, 612 Ridgely Avenue, Suite 401,

Annapolis, Maryland, United States

Site Status

Chevy Chase Clinical Research, 5550 Friendship Blvd.

Chevy Chase, Maryland, United States

Site Status

Commonwealth Clinical Studies, 189 Quincy St.

Brockton, Massachusetts, United States

Site Status

Center For Digestive Health

Troy, Michigan, United States

Site Status

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

Wyoming, Michigan, United States

Site Status

Ehrhardt Clinical Research, LLC, 108 Congress Street

Belton, Missouri, United States

Site Status

AGA Clinical Research Associates, Inc., 3205 Fire Road

Egg Harbor, New Jersey, United States

Site Status

Holy Name Medical Center, 718 Teaneck Road

Teaneck, New Jersey, United States

Site Status

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

Great Neck, New York, United States

Site Status

NYU Langone Long Island , 1000 Northern Boulevard, Suite 160

Great Neck, New York, United States

Site Status

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

New York, New York, United States

Site Status

Montefiore Medical Center, 111 East 210th Street

The Bronx, New York, United States

Site Status

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

Chapel Hill, North Carolina, United States

Site Status

Ohio GI and Liver Institute, 2925 Vernon Place 100

Cincinnati, Ohio, United States

Site Status

Ohio GI and Liver Institute

Cincinnati, Ohio, United States

Site Status

ClinSearch, 6035 Shallowford Road, Suite 109

Chattanooga, Tennessee, United States

Site Status

Brooke Army Medical Center, 3551 Roger Brooke Drive

Fort Sam Houston, Texas, United States

Site Status

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

Houston, Texas, United States

Site Status

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

Houston, Texas, United States

Site Status

Spring Gastroenterology Associates, 8901 FM 1960 West

Humble, Texas, United States

Site Status

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

Richardson, Texas, United States

Site Status

Digestive Disease Center, 621 Camden Street, Suite 202

San Antonio, Texas, United States

Site Status

Tyler Research Institute, 1720 S. Beckham

Tyler, Texas, United States

Site Status

Gasteroenterology Associates of Northern Virgina, 3028 Javier Road

Fairfax, Virginia, United States

Site Status

McGuire DVAMC, 1201 Broad Rock Boulevard

Richmond, Virginia, United States

Site Status

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

Bankstown, New South Wales, Australia

Site Status

Department of Gastroenterology and Hepatology, Concord Hospital, Hospital Road

Concord, New South Wales, Australia

Site Status

Nepean Hospital, Derby Street

Kingswood, New South Wales, Australia

Site Status

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

Liverpool, New South Wales, Australia

Site Status

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

Site Status

Mater Hospital Brisbane, Department of Gastroenterology, Raymond Terrace

South Brisbane, Queensland, Australia

Site Status

Ballarat Health Services, Drummond St North

Ballarat, Victoria, Australia

Site Status

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

Box Hill, Victoria, Australia

Site Status

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

Malvern, Victoria, Australia

Site Status

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

Plovdiv, , Bulgaria

Site Status

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

Sliven, , Bulgaria

Site Status

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

Sofia, , Bulgaria

Site Status

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

Sofia, , Bulgaria

Site Status

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

Varna, , Bulgaria

Site Status

Discovery Clinical Services Ltd. 601 A Discovery St.

Victoria, British Columbia, Canada

Site Status

Mount Sinai Hospital, 600 University Avenue, Suite 445

Toronto, Ontario, Canada

Site Status

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

Montreal, Quebec, Canada

Site Status

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

Saskatoon, Saskatchewan, Canada

Site Status

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

Hořovice, , Czechia

Site Status

Gastroenterologie s.r.o., Manesova 646,

Hradec Králové, , Czechia

Site Status

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

Hradec Králové, , Czechia

Site Status

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

Prague, , Czechia

Site Status

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

Prague, , Czechia

Site Status

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

Třebovice, , Czechia

Site Status

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

Ústí nad Labem, , Czechia

Site Status

Assaf HaRofeh Medical Center, Gastroenterology Department, Harofeh Medical Center

Be’er Ya‘aqov, , Israel

Site Status

Bnaizion Medical Center, Golomb 47

Haifa, , Israel

Site Status

The E. Wolfson Medical Center, 62 Halohamim Str.

Holon, , Israel

Site Status

Shaare Zedek Medical Center, Beith Street

Jerusalem, , Israel

Site Status

Ein Karem Medical Center, Kiryat Hadassah

Jerusalem, , Israel

Site Status

Meir, 59 Tchemacovsky St

Kfar Saba, , Israel

Site Status

Galilee Medical Center, P.O.B. 21

Nahariya, , Israel

Site Status

Holy Family Hospital, Namsawi St. POB 8

Nazareth, , Israel

Site Status

RMC Beilinson Hospital, 39 Jabotinsky Street

Petah Tikva, , Israel

Site Status

Sourasky Medical Center, 6 Weizman Street

Tel Aviv, , Israel

Site Status

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

Auckland, , New Zealand

Site Status

Christchurch Hospital

Christchurch, , New Zealand

Site Status

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

Dunedin, , New Zealand

Site Status

Department of Gastroenterology,Waikato Hospital

Hamilton, , New Zealand

Site Status

Clinical Trials Unit, Tauranga Hospital,

Tauranga, , New Zealand

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NZOZ Specjalistyczne Centrum Gastrologii GASTROMED Wiejska 81

Bialystok, , Poland

Site Status

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

Gdansk, , Poland

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

Krakow, , Poland

Site Status

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

Lodz, , Poland

Site Status

Wojewodzki Szpital Kliniczny w Olsztynie Oddzial Gastroenterologiczny Żołnierska 18

Olsztyn, , Poland

Site Status

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

Sopot, , Poland

Site Status

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

Szczecin, , Poland

Site Status

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

Torun, , Poland

Site Status

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

Warsaw, , Poland

Site Status

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

Wroclaw, , Poland

Site Status

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

Belgrade, , Serbia

Site Status

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

Belgrade, , Serbia

Site Status

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

Belgrade, , Serbia

Site Status

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

Kragujevac, , Serbia

Site Status

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

Novi Sad, , Serbia

Site Status

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

Bratislava, , Slovakia

Site Status

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

Bratislava, , Slovakia

Site Status

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

Brezno, , Slovakia

Site Status

PIGEAS s.r.Prieložtek 1, o.,

Martin, , Slovakia

Site Status

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

Nitra, , Slovakia

Site Status

Countries

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

References

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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.

Reference Type DERIVED
PMID: 39199994 (View on PubMed)

Provided Documents

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Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Related Links

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Other Identifiers

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RHB-104-01

Identifier Type: -

Identifier Source: org_study_id