E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subjects will be enrolled suffering from active, moderate to severe Crohn´s disease with a history of small or large bowel disease, with or without colonic disease. Their screening Crohn´s Disease Activity Index (CDAI) shall be between 250 and 450 inclusive and their fasting serum CRP concentration shall be above 7.5 mg/L. |
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MedDRA Classification |
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 efficacy objective of the induction period (first 12 weeks) of this study is to determine the effect on Crohn’s disease severity as measured by Crohn’s Disease Activity Index (CDAI) scores of three doses regimens of CCX282-B compared with placebo, administered orally once daily for up to twelve consecutive weeks to subjects with moderate to severe Crohn’s disease. The primary efficacy objective of the maintenance period (last 36 weeks) of this study is to determine the effect of CCX282-B compared to placebo on maintenance of response as measured by CDAI over a 36-week period. |
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E.2.2 | Secondary objectives of the trial |
Induction Period: -Safety and tolerability of 3 dose of oral regimens of CCX282-B compared with Placebo for up to 12 consecutive weeks -Effect of CCX282-B compared with placebo on: .Histopathological and endoscopic visual appearance of the ileal and colonic Mucosa .Health-related quality of life using Short Form-36 version 2 .Serum C-reactive protein concentrations .Dose-response relationship for effects of 3 dose regimens of CCX282-B on CD activity .If CCX282-B compared with placebo results in reduction in glucocorticoid use .Population pharmacokinetic profile of CCX282-B in subject with moderate to severe CD Maintenance Period: -Safety and tolerability of 250 mg twice daily oral CCX282-B compared with placebo for up to 36 consecutive weeks -Effect of CCX282-B compared with placebo on: .Health-related quality of life using Short Form-36 version 2 .Serum C-reactive protein concentrations .if glucocorticoid use reduced in CCX282-B group versus placebo
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
The subject must meet all of the following inclusion criteria in order to enter the study:
1. The subject is male or female, at least 18 years of age.
2. At study entry the subject has active, moderate to severe Crohn’s disease (documented by X rays or colonoscopy) with evidence of small bowel and/or colonic disease. CDAI at study entry must be between 250 and 450, inclusive. Fasting serum CRP concentration during the Screening period must be above 7.5 mg/L.
3. If the subject has been receiving therapy for Crohn’s disease (methotrexate, azathioprine, 6-mercaptopurine, and/or up to 20 mg per day of prednisone or prednisone-equivalent), s/he must be on a stable regimen of this medication(s) beginning at least four weeks prior to study entry and is expected to continue on a stable dose of these medications throughout at least the first 196 days. Glucocorticoid doses could be tapered after the Study Day 57 visit, and must be tapered after the Study Day 113 visit. 5-ASA therapy for Crohn’s disease is allowed during the study.
4. No more than 100 cm of the subject’s small bowel has been resected.
5. If a female of childbearing potential, or if a male whose partner is a woman of childbearing potential, the subject must agree to use adequate contraception during the 364 days of the study drug administration. Adequate contraception is defined as use by the female partner of any form of hormonal contraception or intra-uterine device, or use by at least one of the partners of a barrier method of contraception witn a spermicide. Promise of abstinence alone is not considered adequate contraception.
6. The subject is willing and able to provide written Informed Consent prior to screening and to comply with the requirements of the study protocol.
7. If taking oral antibiotics chronically, the subject must have been using these continuously for at least 1 month prior to randomization and at stable doses for at least 2 weeks prior to randomization.
All subjects who complete the 12-week induction period of the study will be eligible to enter the active treatment period. Subjects who are in the 28-day follow-up period at the time of implementation of Amendment 1 of the protocol, will also be allowed to enter the 4-week active treatment period following their Day 113F visit. These subjects may come in early for their Day 113F visit. Subjects who have completed the study by the time of implementation of Amendment 1 of the protocol, will also be allowed to enter the 4-week active treatment period, if they are within 3 months after completing the study. These subjects must come to the study center for a Day 113F2 visit. All subjects must sign written informed consent to continue in the active treatment period of the study.
The subject must meet all the following criteria to continue in the maintenance period of the study: 1. CDAI decrease from baseline (measured during screening period) to Day 113 of at least 70 points; 2. If the subject has been receiving therapy for Crohn’s disease (methotrexate, azathioprine, 6-mercaptopurine, and/or up to 20 mg per day of prednisone or prednisone-equivalent), s/he must be on a stable regimen of this medication(s) from Day 113 through at least Day 197. Glucocorticoid doses must be tapered starting at the Study Day 113 visit (see section 9.4.6). 5-ASA therapy for Crohn’s disease is allowed during the study. 3. If a female of childbearing potential, or if a male whose partner is a woman of childbearing potential, the subject must agree to use adequate contraception during the 364 days of the study drug administration. Adequate contraception is defined as use by the female partner of any form of hormonal contraception or intra-uterine device, or use by at least one of the partners of a barrier method of contraception with a spermicide. Promise of abstinence alone is not considered adequate contraception.
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E.4 | Principal exclusion criteria |
Subjects who meet any of the following exclusion criteria may not enter the study:
1. If female, the subject is pregnant or has a positive pregnancy test, or is breast feeding; 2. Medical history of hypersensitivity to any of the components of the CCX282-B formulation (microcrystalline cellulose, polyvinyl pyrrolidone, sodium lauryl sulphate, colloidal silicon dioxide, crospovidone, or sodium stearyl fumarate); 3. The subject used cyclosporine, tacrolimus, sirolimus or mycophenolate mofetil and/or greater than 20 mg prednisone or a prednisone-equivalent during the 4 weeks prior to study entry; 4. The subject received treatment with a TNF inhibitor (e.g., infliximab or adalimumab) or natalizumab within 12 weeks prior to study entry; 5. The subject has received parenteral glucocorticoids or corticotrophin within 4 weeks prior to study entry; 6. The subject received an experimental treatment for Crohn’s disease within 4 weeks prior to study entry; 7. The subject has a known symptomatic obstructive stricture, had bowel surgery (other than appendectomy) within 12 weeks prior to randomization and/or the subject is planned or deemed likely to require abdominal surgery related to Crohn’s disease during the study period; 8. Subjects with ileostomies, colostomies, or rectal pouches; 9. The subject has evidence of short bowel syndrome requiring enteral or parenteral nutritional supplementation or total parenteral nutrition; 10. The subject has evidence of hepatitis B, hepatitis C, and/or the human immunodeficiency virus (HIV) infection based on virology tests; 11. The subject has evidence of active tuberculosis. Chest radiographs may be acquired to rule out tuberculosis. Alternatively a screening test could be done (tuberculin skin test, QuantiFERON-TB Gold test, or T-SPOT™.TB test) to rule out TB. If the screening test is positive, chest radiographs must be obtained to rule out TB. 12. The subject has a history of any infection requiring intravenous antibiotics, a serious local infection (e.g., cellulitis or abscess), systemic infection (e.g., pneumonia, septicemia), or gastrointestinal infection within 12 weeks of randomization; 13. Has a diagnosis of ulcerative or indeterminate colitis; 14. The subject has a history or presence of illicit drug use and/or alcohol abuse within the year prior to study entry; 15. The subject has a history or presence of any form of cancer within the 5 years prior to study entry, with the exception of excised basal cell or squamous cell carcinoma of the skin, or cervical carcinoma in situ or breast carcinoma in situ that has been excised or resected completely and is without evidence of local recurrence or metastasis, and 16. The subject has a history or presence of any medical or psychiatric condition or disease, or laboratory abnormality that, in the opinion of the Investigator, may place the subject at unacceptable risk for study participation and may prevent the subject from completing the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
For the induction period of the study, the primary efficacy endpoint is the attainment of a clinical response (defined as a decrease from baseline in CDAI score of at least 70) at Day 57.
For the maintenance period of the study, the primary efficacy endpoint is the attainment of a CDAI delta 70 response at the end of the active treatment period (Day 113) AND maintenance of the CDAI response at Study Day 365 (Day 197 for the interim analysis). Loss of CDAI response during the maintenance period is defined as a CDAI increase, at any time, of more than 70 points from the Day 113 value and an absolute CDAI value above 250, at any time, or the need for intervention after Day 113.
Since there is no comparator group for the active treatment period, results from this period will only be summarized descriptively. This will include a summary of the CDAI and CRP changes during the active treatment period, as well as tapering/discontinuation of corticosteroid use during the active treatment period.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
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 | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
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.8.3 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 57 |
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 | Information not present in EudraCT |
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 |
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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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Last visit of last patient |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 1 |