Study to evaluate whether a fixed-dose of RHB-104 is safe and effective in subjects suffering from moderate to Severely 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: 28 February 2019
• Main ID: EUCTR2015-001179-36-SK
• Date of registration: 21/11/2016
• 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 to Severely 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 to Severely Active Crohn’s Disease. - RHB-104-01
• Date of first enrolment: 13/01/2017
• Target sample size: 324
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-001179-36
• 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

Australia, Bulgaria, Canada, Czech Republic, Israel, New Zealand, Poland, Romania, Serbia, Slovakia, United States

Contacts

• Name: Medical Director - Ira Kalfus
• Affiliation: RedHill Biopharma Ltd.

• Name: Medical Director - Ira Kalfus
• Affiliation: RedHill Biopharma Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
•Males and females 18 to 75 years of age.
•Signed fully informed consent provided as per this protocol.
•Diagnosis of Crohn’s Disease confirmed by endoscopy or radiography and/or histology at least 6 months prior to randomization into the study.
•CD involving the ileum and/or colon
•Moderately to severely active CD (Crohn’s Disease Activity Index (CDAI) score of = 220 and =450) at baseline.
•Current treatment with at least one of the following therapies:
- Oral 5-aminosalicylic acid (5-ASA) compounds. Dose must be stable for at least 4 weeks before baseline.
- Corticosteroid therapy. Dose must be stable for at least 2 weeks before baseline.
- Azathioprine or 6-mercaptopurine (6-MP) or methotrexate. Dose must be stable for at least 8 weeks before baseline.
- Infliximab or adalimumab. Dose must be stable for at least 14 weeks before baseline.
• White blood cell count = 3.5x10 exp 9 at screening.
• 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 (MRE or CTE) or endoscopic confirmation of the presence of active CD within 5 weeks of screening visit.
•Subject agrees to use the following effective contraceptive methods only
- diaphragm, cervical cap, contraceptive sponge or condom with
spermicidal foam/gel/cream/suppository
- IUD/IUS
- 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. In regions where local regulatory contraceptive requirements differ, the ICF will reflect local policies.

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 288
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 36

Exclusion criteria:
•Crohn’s Disease involvement isolated to the mouth, upper gastrointestinal tract, or anus.
•History of total colectomy with ileorectal anastomosis or a proctocolectomy.
•Presence of active fistulizing Crohn’s Disease or healed fistula within 2 months prior to screening.
•Subject has postoperative stoma, ostomy, or ileoanal pouch.
•Subject has short bowel syndrome.
•Subject is scheduled for surgical bowel resection.
•Subject has known symptomatic obstructive strictures or bowel perforation in the 6 months prior to screening.
•Change in dose or discontinuation of oral 5-aminosalicylic acid (5-ASA) compounds less than 4 weeks prior to baseline.
•Change in dose or discontinuation of corticosteroids less than 2 weeks prior to baseline.
•Change in dose or discontinuation of azathioprine, 6-mercaptopurine (6-MP) or methotrexate less than 8 weeks prior to baseline.
•Change in dose or discontinuation of infliximab or adalimumab less than 14 weeks prior to baseline.
•Treatment with vedolizumab less than 120 days prior to baseline or biological therapies (apart from infliximab or adalimumab) less than 60 days prior to baseline.
•Previous treatment with rifabutin and/or clofazimine.
•Oral or parenteral antibiotics in the 4 weeks prior to baseline (topical antibiotics are permitted).
•Treatment with probiotics (excluding yogurt and yogurt-derived products) in the 4 weeks prior to baseline.
•Females who have a positive pregnancy test or are lactating.



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

Health Condition(s) or Problem(s) studied

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

Moderately to Severely Active Crohn's Disease
MedDRA version: 20.0 Level: PT Classification code 10011401 Term: Crohn's disease System Organ Class: 10017947 - Gastrointestinal disorders

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)

Secondary Objective: Assess whether subjects randomized to receive RHB-104 have a higher
probability of being in a state of
1) response at the 26 week assessment
2) remission at the 52 week assessment
3) remission in assessments from week 26 through week 52
4) remission at the 16 week assessment
5) steroid free remission at the 52 week assessment (subjects must be
maintained off steroids for 3 weeks in order to be determined to be in
steroid free remission e.g. by week 49.)
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.

Timepoint(s) of evaluation of this end point: Week 26

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.

Secondary Outcome(s)

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

Timepoint(s) of evaluation of this end point: Week 26

Secondary ID(s)

2015-001179-36-PL

RHB-104-01

Source(s) of Monetary Support

RedHill Biopharma Ltd.

Ethics review

Status: Approved
Approval date:
Contact: