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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03009396
• Date of registration: 26/12/2016
• Prospective Registration: Yes
• Primary sponsor: RedHill Biopharma Limited
• Public title: Open Label Efficacy and Safety of Anti-MAP (Mycobacterium Avium Ssp. Paratuberculosis) Therapy in Adult Crohn's Disease MAPUS2
• Scientific 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
• Date of first enrolment: March 18, 2017
• Target sample size: 54
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03009396
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Canada, Czechia, Israel, New Zealand, Poland, Serbia, United States

Contacts

• Name: Ira N Kalfus, MD
• Affiliation: RedHill Biopharma Limited

• Name: David Y Graham, MD
• Affiliation: Department of Medicine / Gastroenterology, Baylor College of Medicine, Houston

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: 76 Years
Gender: All

Health Condition(s) or Problem(s) studied

Crohn Disease

Intervention(s)

Drug: RHB-104; a fixed-dose combination of 95 mg clarithromycin, 45 mg rifabutin, and 10 mg clofazimine

Primary Outcome(s)

Remission [Time Frame: 16 weeks]

Secondary Outcome(s)

Duration of remission [Time Frame: Baseline through week 52]

Time to response [Time Frame: Baseline through week 52]

Duration of response [Time Frame: Baseline through week 52]

Maintenance of Remission [Time Frame: Baseline through week 52]

Time to remission [Time Frame: Baseline through week 52]

Secondary ID(s)

RHB-104-04

Source(s) of Monetary Support

Please refer to primary and secondary sponsors