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Trial record 2 of 3 for:    RHB-104

Open Label Efficacy and Safety of Anti-MAP (Mycobacterium Avium Ssp. Paratuberculosis) Therapy in Adult Crohn's Disease (MAPUS2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03009396
Recruitment Status : Enrolling by invitation
First Posted : January 4, 2017
Last Update Posted : January 19, 2018
Sponsor:
Information provided by (Responsible Party):

Study Description
Brief Summary:
An open label extension to the RHB-104-01 Study.

Condition or disease Intervention/treatment Phase
Crohn Disease Drug: RHB-104 Phase 3

Detailed Description:
An Open Label Phase III Study to Assess the Efficacy and Safety of Fixed-Dose Combination RHB-104 in Subjects with Active Crohn's Disease Despite 26 Weeks of Participation in the MAP US RHB-104-01 Study.

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open Label Study to Assess the Efficacy and Safety of Fixed-Dose Combination RHB-104 in Subjects With Active Crohn's Disease Despite 26 Weeks of Participation in the MAP US RHB-104-01 Study
Actual Study Start Date : March 18, 2017
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : October 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Crohn's Disease
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: Active therapy
RHB-104; a fixed-dose combination of 95 mg clarithromycin, 45 mg rifabutin, and 10 mg clofazimine
Drug: RHB-104
RHB-104; a fixed-dose combination of 95 mg clarithromycin, 45 mg rifabutin, and 10 mg clofazimine


Outcome Measures

Primary Outcome Measures :
  1. Remission [ Time Frame: 16 weeks ]
    Reduction of the total Crohn's Disease Activity Index (CDAI) score to less than 150


Secondary Outcome Measures :
  1. Time to remission [ Time Frame: Baseline through week 52 ]
    The time (weeks after randomization) that a subject first records a state of remission.

  2. Duration of remission [ Time Frame: Baseline through week 52 ]
    The time that a subject is in a state of remission.

  3. Maintenance of Remission [ Time Frame: Baseline through week 52 ]
    Remission in a subject from week 16 through week 52.

  4. Duration of response [ Time Frame: Baseline through week 52 ]
    The time that a subject is in a state of response.

  5. Time to response [ Time Frame: Baseline through week 52 ]
    The time (weeks after randomization) that a subject first records a state of response.


Other Outcome Measures:
  1. MAP Detection at Baseline [ Time Frame: Baseline ]
    Proportion of subjects with a MAP positive blood PCR assay at baseline

  2. Changes in MAP blood status [ Time Frame: Baseline through week 52 ]
    Changes in MAP blood status by polymerase chain reaction (PCR)

  3. CDEIS Changes in Those Subjects Who Undergo Colonoscopy [ Time Frame: 16 and 52 weeks ]
    Change from baseline in the mean Crohn's Disease Endoscopic Index of Severity (CDEIS) after 16 and 52 weeks of treatment

  4. SES-CD Changes in Those Subjects Who Undergo Colonoscopy [ Time Frame: 16 and 52 weeks ]
    Change from baseline in the mean Simple Endoscopic Activity Score (SES-CD) after 16 and 52 weeks of treatment

  5. CDEIS and SES-CD comparison in Those Subjects Who Undergo Colonoscopy [ Time Frame: 52 weeks ]
    Success rates of (∆CDEIS and SES-CD) defined by 25% and 50% improvements

  6. CDEIS and SES-CD correlation among those Subjects Who Undergo Colonoscopy [ Time Frame: 16 and 52 weeks ]
    Correlation between the change from baseline in the endoscopic index (∆SES-CD) and the clinical index (∆CDAI) after 16 and 52 weeks of treatment

  7. Endoscopic Changes in Those Subjects Who Undergo Colonoscopy [ Time Frame: 52 weeks ]
    Comparison of success rates of (∆CDEIS) defined by 25% and by 50% improvements in SES-CD vs CDAI defined response

  8. Change in Inflammatory Bowel Disease Quality of Life [ Time Frame: 16, 26 and 52 weeks ]
    Change in Inflammatory Bowel Disease Questionnaire (IBDQ) and Short Form 36 (SF-36)

  9. Change in inflammatory markers [ Time Frame: Baseline through 52 weeks ]
    Changes from baseline in a serum markers of inflammation: C-reactive Protein (CRP) and fecal calprotectin

  10. Safety [ Time Frame: 52 weeks ]
    Number of subjects with adverse events as a measure of safety and tolerability


Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 76 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed fully informed consent provided as per this protocol.
  • Participation in RHB-104-01 for 26 weeks, and a Crohn's Disease Activity Index (CDAI) score of ≥ 150 at Visit Week 26.

OR

  • More than 26 weeks, with a CDAI ≥150 at Visit Week 26 and all subsequent visits, and subject is between Week 26 and 52 within 4 weeks (28 days) of site activation (e.g. Subject with CDAI = 249 at week 26 and who is at week 38 at the time of site's activation for RHB-104-04 has a 4-week window to be enrolled in the open label study via the Optional Screening Visit)
  • Current treatment with at least one of the following therapies which may be discontinued by the investigator as clinically indicated after 8 weeks of open label RHB-104 treatment:

    • Oral 5-acetyl salicylic acid (5-ASA) compounds
    • Azathioprine or 6-mercaptopurine (6-MP) or methotrexate
    • Infliximab or adalimumab OR Current treatment with corticosteroid therapy which must begin tapering after 4 weeks of treatment with open label RHB-104 (Refer to Appendix 13)
  • White blood cell count ≥ 3.5x109 at screening (RHB-104-01 Visit Week 26 visit or Optional Screening visit)
  • Subject agrees to use the following effective contraceptive methods

    • diaphragm, cervical cap, contraceptive sponge or condom) with spermicidal foam/gel/cream/suppository
    • IUD (intrauterine device) /IUS (intrauterine system)
    • progestogen injection (Depo-Provera®) throughout the study and for at least 6 weeks after last study drug administration, unless subject or partner of subject is post-menopausal or otherwise incapable of becoming pregnant by reason of surgery or tubal ligation, or has had a vasectomy. Post-menopausal is defined as having experienced 12 consecutive months without menstruation.

In regions where local regulatory contraceptive requirements differ, the ICF (Informed Consent Form) will reflect local policies.

Exclusion Criteria:

  1. Positive stool results for C. difficile.
  2. Currently diagnosed or history of uveitis confirmed by either an ophthalmologist or optometrist.
  3. Treatment with any medication that causes QT prolongation or Torsades de Pointes, including but not limited to: amiodarone, amitriptyline, astemizole, cisapride, citalopram dose greater than 20 mg/day, dihydroergotamine, disopyramide, dofetilide, dronedarone, ergotamine, ibutilide, ondansetron or other 5-HT3 (5-hydroxytryptamine) receptor antagonists, pimozide, procainamide, quinidine, quinine, quinolones, ranolazine, risperidone, sotalol, terfenadine and tolterodine. QT prolonging drugs may be referenced at the CredibleMeds® web site: https://crediblemeds.org/index.php/drugsearch/
  4. Treatment with the following CYP3A4 interactive medications: alfentanyl, alprazolam, amlodipine, anti-retroviral agents, apixaban, aprepitant, aripiprazole, atorvastatin, boceprevir, buspirone, carbamazepine, carvedilol, colchicine, cyclosporine, digoxin, diltiazem, estrogens, felodipine, fluconazole, fluvoxamine, grapefruit juice, haloperidol, ketoconazole, lovastatin, lurasidone, metoprolol, nefazodone, nifedipine, nisoldipine, nitrendipine, propranol, roflumilast, simvastatin, St. John's wort, and voriconazole.
  5. Any evidence of any newly diagnosed significant hematological, hepatic, renal, cardiac, pulmonary, metabolic, neurological, psychiatric or other disease (e.g. porphyria) that might interfere with subject's ability to safely enter and or complete the study requirements.
  6. Females who have a positive pregnancy test or are lactating.
  7. Refusal to sign the study informed consent form.
  8. Inability to be able to adequately communicate with the investigator or their respective designee and/or comply with the requirements of the entire study.
  9. Clinically significant abnormalities of hematology or biochemistry as confirmed by repeat testing based on investigator's discretion, including but not limited to, elevations greater than 2 times the upper limit of normal of Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP) or creatinine clearance less than 60 ml/min at screening via estimated Cockcroft-Gault formula:

    Creatinine Clearance = [140 - age in years] * weight (kg) / 72 * Serum Creatinine (mg/dl) [multiply estimated rate by 0.85 for women], using actual body weight.

  10. QTcF (shortening of the QT interval in the heart rate) >450ms in males and QTcF>460ms in females, bundle branch block, or major ST or T wave abnormalities that make the assessment of the QT impossible.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03009396


Locations
United States, California
Digestive Care Associates, Inc., 1000 Laurel Street
San Carlos, California, United States, 94070
United States, Georgia
Gastrointestinal Specialists of Georgia PC 711 Canton Rd. #300
Marietta, Georgia, United States, 30060
United States, Kansas
Cotton-O'Neil Clinical Research Center, 720 SW Lane St.
Topeka, Kansas, United States, 66606
United States, Maryland
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, Tennessee
ClinSearch 6035 Shallowford Road Suite 109
Chattanooga, Tennessee, United States, 37421
Canada, British Columbia
Discovery Clinical Services Ltd., 601 A Discovery St.
Victoria, British Columbia, Canada, V8T 5G4
Israel
Ha'Emek Medical Center, Institute of Gastroenterology and Liver diseases, 21 Yitshak Rabin Boulevard
Afula, Israel, 1834111
Gastroenterology Institute, Division of Medicine, Hadassah - Hebrew University Medical Center POB 12000
Jerusalem, Israel, 91120
Meir Medial Center, 59 Tchemacovsky St.
Kfar-Saba, Israel, 44281
New Zealand
Christchurch Hospital, 2 Riccarton Rd.
Christchurch, Canterbury, New Zealand, 80011
Waikato Hospital, Department of Gastroenterology, Level B1, Menzies Building, Pembroke Street
Hamilton, Waikato, New Zealand, 3240
Poland
NZOZ Specjalistyczne Centrum Gastrologii GASTROMED, Wiejska 81
Białystok, Poland, 15-351
Samodzielny Publiczny Zakład Opieki Zdrowotnej MSW W Gdańsku Oddział Gastroenterologiczny, Ul. Kartuska 4/6
Gdansk, Poland, 80-104
UNICARDIA Specjalistyczne Centrum Leczenia Chorob Serca i Naczyn & UNIMEDICA. Specjalistyczne Centrum Medyczne Sp. z o.o., Kluczborska 15
Kraków, Poland, 31-271
Wojewodzki Szpital Kliniczny w Olsztynie Oddzial Gastroenterologiczny, Zolnierska 18
Olsztyn, Poland, 10-561
EuroMedis sp. z.o.o., Al. Powstancow Wielkopolskich 33a
Szczecin, Poland, 70-111
Centralny Szpital Kliniczny MSW w Warszawie. Klinika Chorob Wewnetrznych i Gastroenterologii, Woloska 137,
Warsaw, Poland, 02-507
ARS MEDICA s.c., Powstancow Slaskich 56A/2
Wroclaw, Poland, 53-333
Serbia
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 Kragujevac, Zmaj Jovina 30
Kragujevac, Serbia, 34000
Sponsors and Collaborators
RedHill Biopharma Limited
Investigators
Study Director: Ira N Kalfus, MD RedHill Biopharma Ltd.
Principal Investigator: David Y Graham, MD Department of Medicine / Gastroenterology, Baylor College of Medicine, Houston
More Information

Additional Information:
Responsible Party: RedHill Biopharma Limited
ClinicalTrials.gov Identifier: NCT03009396     History of Changes
Other Study ID Numbers: RHB-104-04
First Posted: January 4, 2017    Key Record Dates
Last Update Posted: January 19, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by RedHill Biopharma Limited:
Crohn's Disease,
moderate to severe
remission
Mycobacterium avium paratuberculosis
antibiotic

Additional relevant MeSH terms:
Crohn Disease
Mycobacterium avium-intracellulare Infection
Paratuberculosis
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Mycobacterium Infections, Nontuberculous
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections