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Trial record 3 of 12 for:    RedHill Biopharma

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 : Completed
First Posted : January 4, 2017
Last Update Posted : April 1, 2020
Sponsor:
Information provided by (Responsible Party):
RedHill Biopharma Limited

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

Condition or disease Intervention/treatment Phase
Crohn Disease Drug: RHB-104; a fixed-dose combination of 95 mg clarithromycin, 45 mg rifabutin, and 10 mg clofazimine 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 54 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Active
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
Actual Primary Completion Date : November 13, 2018
Actual Study Completion Date : August 19, 2019


Arm Intervention/treatment
Experimental: RHB-104
RHB-104; a fixed-dose combination of 95 mg clarithromycin, 45 mg rifabutin, 10 mg clofazimine
Drug: RHB-104; a fixed-dose combination of 95 mg clarithromycin, 45 mg rifabutin, and 10 mg clofazimine
For patients who are not in remission after 26 weeks in the RHB-104-01 study




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. Number of subjects with adverse events as a measure of safety and tolerability [ Time Frame: 52 weeks ]
    Comparison of adverse events and serious adverse events in the active therapy arm throughout the study compared to the placebo controlled arm.



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.


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Ages Eligible for Study:   18 Years to 76 Years   (Adult, Older Adult)
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.

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
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Sponsors and Collaborators
RedHill Biopharma Limited
Investigators
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Study Director: Ira N Kalfus, MD RedHill Biopharma Ltd.
Principal Investigator: David Y Graham, MD Department of Medicine / Gastroenterology, Baylor College of Medicine, Houston

Additional Information:
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Responsible Party: RedHill Biopharma Limited
ClinicalTrials.gov Identifier: NCT03009396    
Other Study ID Numbers: RHB-104-04
First Posted: January 4, 2017    Key Record Dates
Last Update Posted: April 1, 2020
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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:
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Paratuberculosis
Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Clarithromycin
Rifabutin
Clofazimine
Anti-Bacterial Agents
Anti-Infective Agents
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Inflammatory Agents
Leprostatic Agents