E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 |
To evaluate the efficacy of SHR0302 compared to placebo in inducing clinical remission at Week 12. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the safety and tolerability of oral SHR0302 • To evaluate the efficacy of oral SHR0302 in inducing clinical remission at different time points • To evaluate the efficacy of oral SHR0302 in inducing endoscopy response • To evaluate the change from baseline in the following biomarkers; CRP, fecal calprotectin. • To characterise the pharmacokinetics of oral SHR0302 and explore the correlation of exposure-response |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male or Female age ≥ 18 and ≤75 years of age at randomization. • Subjects with a documented at least three-month history of diagnosed ileal, colonic, or ileocolonic Crohn’s Disease at the time of randomization. • Currently having Crohn’s Disease with Crohn’s Disease Activity Index (CDAI) score ≥ 220 to ≤450. |
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E.4 | Principal exclusion criteria |
• Diagnosis of indeterminate colitis, or clinical findings suggestive of Ulcerative Colitis. • Subject with CD with stoma, gastric or ileoanal pouch, proto-colectomy or total colectomy, symptomatic stenosis or stricture, history of bowel perforation, suspected abscess; actively draining fistula. • Treatment naïve subjects diagnosed with Crohn’s disease (without previous exposure to any of the following therapies for CD treatment: 5- ASA, corticosteroids, immune-suppressants, or biological treatment). |
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E.5 End points |
E.5.1 | Primary end point(s) |
The percentage of subjects achieving clinical remission at week 12, defined as Crohn’s Disease Activity Index (CDAI) score < 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) |
- The percentage of subjects achieving clinical remission defined as mean daily stool frequency (SF) ≤2.5, and abdominal pain (AP) ≤ 1 using the Patient Reported Outcome from CDAI at week 1, 4, 8, 12, 13, 16, and 24.
- The percentage of subjects achieving clinical remission defined as PRO2 < 8 at week 1, 4, 8, 12, 13, 16, and 24.
- The percentage of subjects achieving clinical response defined as a CDAI decrease from baseline of ≥ 70 points at Week1, 4, 8, 12, 13, 16, and 24.
- The percentage of subjects achieving clinical remission, defined as CDAI of < 150 points at Week 1, 4, 8, 13, 16 and 24.
- Change from baseline in CDAI at Week1, 4, 8, 12, 13, 16 and 24.
- The percentage of subjects achieving endoscopic remission defined as Simple Endoscopy Score for Crohn’s Disease (SES-CD) score ≤ 4, with “ulcerated surface” subscore no greater than 1 in any segment at Week 12. - The percentage of subjects achieving endoscopic remission defined as Simple Endoscopy Score for Crohn's Disease (SES-CD) score of 0-2 or SES-CD score ≤ 4 and at least 2-point reduction from baseline with no subscore >1 at Week 12. - The percentage of subjects achieving endoscopic response at Week 12, defined as a reduction of Simple Endoscopy Score for Crohn's Disease (SES-CD) score by at least 50% from baseline.
- The percentage of subjects achieving mucosal healing as defined by a Simple Endoscopy Score for Crohn's Disease (SES-CD) score equal to 0 at Week 12.
- The Change from baseline in endoscopic Simple Endoscopy Score for Crohn's Disease (SES-CD) score at Week 12.
- Change from baseline in the level of biomarkers CRP, fecal calprotectin.
- The percentage of subjects achieving clinical response defined as a CDAI decrease from baseline of ≥ 100 points at week 1, 4, 8, 12, 13, 16, and 24.
- The systemic exposure of SHR0302 in steady state (i.e. concentration and area under the curve).
Safety Endpoints • To evaluate the safety and tolerability by laboratory parameters. • To evaluate the safety and tolerability by collection of AE/SAE incidence • To measure the vital signs (BP, HR, and Body temperature) • To measure total lipid profile, which includes Triglyceride, LDL and HDL. • To measure thyroid profile; TSH, free T4 and free T3. • 12 –lead ECG.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 12 (unless otherwise noted above) |
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
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 | 4 |
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 | 19 |
E.8.5 | The trial involves multiple Member States | No |
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 |
China |
Poland |
Ukraine |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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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Th end of the trial is defined as the date of the last subject’s last visit or the actual date of follow up visit/contact, whichever is later. |
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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 | 6 |
E.8.9.1 | In the Member State concerned days | 8 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 14 |