E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderately to Severely Active Crohn's Disease |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10011401 |
E.1.2 | Term | Crohn's disease |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Title: Colonoscopy, Biopsy and Crohn's Disease Endocopic Index of Severity (CDEIS/SES-CD) sub-study.
Objectives:
- Change from baseline in the mean Crohn's Disease Endoscopic Index of
Severity (CDEIS and SES-CD) after 26 weeks of treatment
- Correlation between the change from baseline in the endoscopis index
(ΔCDEIS and ΔSES-CD) and the clinical index (ΔCDAI) after 26 weeks of
treatment
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E.3 | Principal 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.
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E.4 | Principal 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
Remission (primary outcome measure) – Remission in a subject is defined as a CDAI score of <150. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Response - A response in the individual subject is defined as reduction in CDAI score of ≥100 from Baseline |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 34 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Bulgaria |
Canada |
Czech Republic |
Israel |
New Zealand |
Poland |
Romania |
Serbia |
Slovakia |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |