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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)

This study is currently recruiting participants.
Verified December 2016 by RedHill Biopharma Limited
Sponsor:
ClinicalTrials.gov Identifier:
NCT03009396
First Posted: January 4, 2017
Last Update Posted: September 21, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
RedHill Biopharma Limited
  Purpose
An open label extension to the RHB-104-01 Study.

Condition Intervention Phase
Crohn Disease Drug: RHB-104 Phase 3

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by RedHill Biopharma Limited:

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


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

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

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

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

  • 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:
  • MAP Detection at Baseline [ Time Frame: Baseline ]
    Proportion of subjects with a MAP positive blood PCR assay at baseline

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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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)

  • 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

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


Estimated Enrollment: 100
Actual Study Start Date: March 18, 2017
Estimated Study Completion Date: October 2019
Estimated Primary Completion Date: June 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.
  Eligibility

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


Contacts
Contact: Ira N Kalfus, MD 917 817 7517 ira@redhillbio.com
Contact: Clara Fehrmann, MS clara@redhillbio.com

Locations
United States, California
Digestive Care Associates, Inc., 1000 Laurel Street Recruiting
San Carlos, California, United States, 94070
Contact: Scott Levenson, MD    650-596-8800    scottlevenson@sbcglobal.net   
Principal Investigator: Scott Levenson, MD         
United States, Georgia
Gastrointestinal Specialists of Georgia PC 711 Canton Rd. #300 Recruiting
Marietta, Georgia, United States, 30060
Contact: September Wynne    678-819-4221    sayers@gigeorgia.com   
Principal Investigator: Aasim Sheikh, MD         
United States, Kansas
Cotton-O'Neil Clinical Research Center, 720 SW Lane St. Not yet recruiting
Topeka, Kansas, United States, 66606
Contact: Amy Neeley    785-270-4885    aneeley@stormontvail.org   
Principal Investigator: Thomas Welton, MD         
United States, Maryland
Chevy Chase Clinical Research, 5550 Friendship Blvd. Not yet recruiting
Chevy Chase, Maryland, United States, 20815
Contact: Erin Klepeis, BS, MSHS    301-652-5520    erin.klepeis@capitaldigestivecare.com   
Principal Investigator: Robert Hardi, MD,AGAF,CPI         
United States, Massachusetts
Commonwealth Clinical Studies, 189 Quincy St. Recruiting
Brockton, Massachusetts, United States, 02302-2926
Contact: Estelle Crowley    508-588-9900      
Principal Investigator: Mark Finkelstein, MD         
United States, Tennessee
ClinSearch 6035 Shallowford Road Suite 109 Recruiting
Chattanooga, Tennessee, United States, 37421
Contact: Vickie Leathers    423-648-4554    vleathers@clinsearch-us.com   
Principal Investigator: Richard Krause, MD         
Canada, British Columbia
Discovery Clinical Services Ltd., 601 A Discovery St. Not yet recruiting
Victoria, British Columbia, Canada, V8T 5G4
Contact: Lisa Warke    250-386-0023    lwarke@dresearch.ca   
Principal Investigator: Denis Petrunia, MD         
Israel
Ha'Emek Medical Center, Institute of Gastroenterology and Liver diseases, 21 Yitshak Rabin Boulevard Recruiting
Afula, Israel, 1834111
Contact: Ayelet Arzi    972-4-6495646    ayelet_ar@clalit.org.il   
Principal Investigator: Eran Zittan, MD         
Gastroenterology Institute, Division of Medicine, Hadassah - Hebrew University Medical Center POB 12000 Recruiting
Jerusalem, Israel, 91120
Contact: Nilly Fardian    972 2 6777595    nillyfardi@gmail.com   
Principal Investigator: Eran Israeli, MD         
Meir Medial Center, 59 Tchemacovsky St. Recruiting
Kfar-Saba, Israel, 44281
Contact: Rinat Yassur Berkovich    +972 9 7471017    rinat.yassur@clalit.org.il   
Principal Investigator: Fred Konikoff, MD         
Poland
Wojewodzki Szpital Kliniczny w Olsztynie Oddzial Gastroenterologiczny, Zolnierska 18 Recruiting
Olsztyn, Poland, 10-561
Contact: Ana Wos, MD    +48 515 320823    annawos1982@gmail.com   
Principal Investigator: Tomasz Arlukowicz, MD, PhD         
EuroMedis sp. z.o.o., Al. Powstancow Wielkopolskich 33a Recruiting
Szczecin, Poland, 70-111
Contact: Wojciech Marlicz, MD, PhD    +48 91 813 6322    marlicz@hotmail.com   
Principal Investigator: Wojciech Marlicz, MD, PhD         
ARS MEDICA s.c., Powstancow Slaskich 56A/2 Recruiting
Wroclaw, Poland, 53-333
Contact: Barbara Wozniak-Stolarska, MD    48 71 373 8929    basiastolarska@interia.pl   
Principal Investigator: Barbara Wozniak-Stolarska, MD         
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 Submitted: December 26, 2016
First Posted: January 4, 2017
Last Update Posted: September 21, 2017
Last Verified: December 2016
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


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