Study to evaluate whether a fixed-dose of RHB-104 is safe and effective in subjects suffering from moderate Crohn’s disease. Subjects will be separated in two groups that will be treated in parallel to receive study drug or placebo. Neither the treating physician nor the subject will be aware of the actual treatment received.

• Register: EUCTR
• Last refreshed on: 29 August 2016
• Main ID: EUCTR2014-004108-31-HU
• Date of registration: 28/04/2015
• Prospective Registration: Yes
• Primary sponsor: RedHill Biopharma Ltd.
• Public title: Study to evaluate whether a fixed-dose of RHB-104 is safe and effective in subjects suffering from moderate Crohn’s disease. Subjects will be separated in two groups that will be treated in parallel to receive study drug or placebo. Neither the treating physician nor the subject will be aware of the actual treatment received.
• Scientific title: A Phase III 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 Active Crohn’s Disease - MAP EU
• Date of first enrolment: 27/08/2015
• Target sample size: 360
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-004108-31
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Czech Republic, Germany, Hungary, Ireland, Netherlands, Russian Federation, Slovakia, Spain, Ukraine, United Kingdom

Contacts

• Name: Medical Director
• Affiliation: RedHill Biopharma Ltd.

• Name: Medical Director
• Affiliation: RedHill Biopharma Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Males and females 18 to 75 years of age.
2. Able to adequately communicate with the investigator or their respective designee and/or comply with the requirements of the entire study.
3. Be willing to provide written informed consent (IC) as evidenced by signature on an informed consent document approved by an institutional review board (IRB) or independent ethics committee (IEC).
4. Diagnosis of Crohn’s disease confirmed by endoscopy or radiography and/or histology at least 6 months prior to randomization into the study.
5. CD involving the ileum and/or colon.
6. Moderately active Crohn’s Disease Activity Index (CDAI) score of =220 and =450 at Visit 1.
7. Treatment with at least one of the following therapies at screening:
- Oral 5-acetyl salicylic acid (5-ASA) compounds: Dose must be stable for at least 4 weeks
- Corticosteroid therapy: Dose must be stable for at least 2 weeks
- Azathioprine or 6-mercaptopurine (6-MP) or methotrexate: Dose must be stable for at least 8 weeks
- Infliximab or adalimumab: Dose must be stable for at least 8 weeks
8. White blood cell count = 3.5x10^9 at screening.
9. Active Crohn’s disease, defined by at least one of the following: C-reactive protein > Upper Limit of Normal (ULN) at screening, fecal calprotectin > Upper Limit of Normal (ULN) at screening, OR radiographic (CTE or MRE) OR endoscopic with photographic confirmation of the presence of active CD within 4 weeks of screening visit. Upon approval of the medical monitor, screening colonoscopy and baseline visit may be performed up to 6 weeks after the screening visit.
10. Subject agrees to use barrier contraceptive methods (i.e. diaphragm, cervical cap, contraceptive sponge or condom) with spermicidal foam/gel/cream/suppository, or IUD 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 330
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

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. Subject has postoperative stoma, ostomy, or ileoanal pouch.
4. Any fistulizing Crohn’s Disease other than asymptomatic internal fistulae, simple (non- draining) perianal fistulae without inflammation or healed fistula.
5. Subject has short bowel syndrome.
6. Subject is scheduled for surgical bowel resection or is anticipated to require surgical intervention for CD during the study.
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 screening.
9. Change in dose or discontinuation of corticosteroids less than 2 weeks prior to screening.
10. Change in dose or discontinuation of azathioprine, 6-mercaptopurine (6-MP) or methotrexate less than 4 weeks prior to screening
11. Treatment with vedolizumab < 120 days prior to screening or other biological therapies (infliximab, adalimumab are allowed at a stable dose for at least 8 weeks) < 60 days prior to screening.
12. Treatment with any medication that causes QT prolongation or Torsades de Pointes within 7 days prior to initiation of study drug.
13. Treatment with the outlined medications within 7 days prior to initiation of study drug.
14. Previous treatment with amiodarone.
15. Previous treatment with rifabutin and/or clofazimine.
16. Oral or parenteral antibiotics in the 4 weeks prior to screening (topical antibiotics are permitted).
17. Treatment with probiotics (excluding yogurt and yogurt-derived products) in the 4 weeks prior to screening.
18. Concomitant use of cyclosporine administered within the previous 8 weeks prior to screening.
19. Chronic use of oral or systemic corticosteroid therapy for other disease(s) e.g. pulmonary diseases. Stable inhaled corticosteroids are permitted.
20. Adverse reaction or hypersensitivity to the study drug or any medications related to the study drug.
21. Positive stool results for C. difficile, other pathogens including ova, or parasites.
22. Positive serology for Hepatitis B, Hepatitis C, or HIV.
• If positive history of previously treated Hepatitis C, but HCV PCR is undetectable off medications for at least 6 months prior to screening, and treating hepatologist or infectious disease specialist believes the subject is cured – subject may be enrolled
23. History of:
• Atypical mycobacterial infections (other than MAP)
• Active tuberculosis requiring treatment in the past 3 years
24. Positive or indeterminate QuantiFERON TB Gold test:
• In the presence of clinical signs/symptoms of TB or high risk of TB infection
25. Currently diagnosed or history of uveitis confirmed by either an ophthalmologist or optometrist.
26. Evidence of any significant hematological, hepatic, renal, cardiac, pulmonary, metabolic, neurological, psychiatric or other disease that might interfere with subject’s ability to safely enter and or complete the study requirements.
27. History of malignancy within the past five years prior to screening except for basal cell carcinoma of the skin or carcinoma in situ of the cervix that has been treated with no evidence of recurrence.
28. Current treatment with total parenteral nutrition.
29. Females who have a positive pregnancy test or are lactating.
30. Hi

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Moderately Active Crohn's Disease
MedDRA version: 18.0 Level: PT Classification code 10011401 Term: Crohn's disease System Organ Class: 10017947 - Gastrointestinal disorders

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Intervention(s)

Product Code: RHB-104
Pharmaceutical Form: Capsule
INN or Proposed INN: Clarithromycin
CAS Number: 81103-11-9
Other descriptive name: CLARITHROMYCIN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 95-
INN or Proposed INN: Rifabutin
CAS Number: 72559-06-9
Other descriptive name: RIFABUTIN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 45-
INN or Proposed INN: Clofazimine
CAS Number: 2030-63-9
Other descriptive name: CLOFAZIMINE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: The primary objective is to assess whether subjects randomized to receive RHB-104 have a higher probability of being in a state of remission at the 26-week assessment as compared to subjects randomized to receive placebo.

Primary end point(s): Remission (primary outcome measure) – Remission in a subject is defined as a CDAI score of <150.

Secondary Objective: Assess whether subjects randomized to receive RHB-104 have a higher probability of being in a state of response at 26 weeks as compared to subjects randomized to receive placebo.

Timepoint(s) of evaluation of this end point: 26 weeks and 52 weeks

Secondary Outcome(s)

Secondary end point(s): Response - A response in the individual subject is defined as reduction in CDAI score of =100 from Visit 1

Timepoint(s) of evaluation of this end point: Visit 1, 26 weeks and 52 weeks

Secondary ID(s)

RHB-104-03

Source(s) of Monetary Support

RedHill Biopharma Ltd.