E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Ulcerative Colitis of the Rectum
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E.1.1.1 | Medical condition in easily understood language |
Ulcerative Colitis of the Rectum
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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 | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045365 |
E.1.2 | Term | Ulcerative colitis |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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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 | 10009900 |
E.1.2 | Term | Colitis ulcerative |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10027682 |
E.1.2 | Term | Immune and associated conditions NEC |
E.1.2 | System Organ Class | 10021428 - Immune system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10021428 |
E.1.2 | Term | Immune system disorders |
E.1.2 | System Organ Class | 10021428 - Immune system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10027665 |
E.1.2 | Term | Immune disorders NEC |
E.1.2 | System Organ Class | 10021428 - Immune system 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 two dosage regimens of the study drug (hydrocortisone acetate 90 mg suppository) administered with the Sephure suppository applicator compared to placebo in the treatment of ulcerative colitis (UC) of the rectum using the Modified Mayo Score.
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E.2.2 | Secondary objectives of the trial |
Reduction of stool frequency and rectal bleeding sub-score of 0 (MMDAI)
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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 |
Pharmacokinetic study Objecive: To evaluate exposure of hydrocortisone acetate and its hydrolysis end product hydrocortisone following single and multiple doses of hydrocortisone acetate 90 mg suppository and to evaluate the relationship, if any, between multiple dose exposures and hypothalamic pituitary adrenal (HPA) axis suppression. All subjects will participate in either the sparse or intensive PK. Plasma hydrocortisone acetate and hydrocortisone concentrations will be analysed after single and multiple doses of the study drug. Intensive PK sampling will be performed on a subgroup of the study population. Sparse PK blood samples will be collected in all study subjects not participating in the intensive PK sub-study as follows: Day 1 (Visit 3): sample 1 at up to 30 minutes pre-dose, sample 2 at 2 hours post-dose and sample 3 at 4 hours post-dose. Day 15 (Visit 5): 1 sample at 8 hours post-dose (morning dose at home) Day 29 (Visit 7): 1 sample at 12 hours after Day 28 evening dose. Intensive PK blood samples will only be collected from subjects participating in the intensive PK sub-study in 4 visits as follows: Day 1: sample 1 at up to 30 minutes pre-dose, sample 2 at 2 hours post-dose, sample 3 at 4 hours post-dose, sample 4 at 8 hours post-dose and sample 5 at 12 hours post-dose. Day 2: 1 sample at 12 hours after Day 1 evening dose Day 28: sample 1 at up to 30 minutes pre-dose, sample 2 at 2 hours post-dose, sample 3 at 4 hours post-dose, sample 4 at 8 hours post-dose and sample 5 at 12 hours post-dose. Day 29: 1 sample at 12 hours after Day 28 evening dose.
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E.3 | Principal inclusion criteria |
Male or non-pregnant, non-lactating females aged 18 years and older. Subjects with a confirmed diagnosis of active UC of the rectum, extending no more than 15 centimeters (cm) (5.9 inches) proximal to the anal verge as assessed by colonoscopy performed at Visit 2. Modified Mayo sub-score for stool frequency of 1-3. Modified Mayo sub-score for rectal bleeding of 0-2. Modified Mayo endoscopic sub-score of 2-3. Total Modified Mayo Score (without physician global assessment) of 3-8.
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E.4 | Principal exclusion criteria |
History or current diagnosis of bacterial or other infectious colitis, radiation-enteritis and radiation-proctitis, Crohn’s disease, collagenous colitis and indeterminate colitis. Prior gastrointestinal surgery except appendectomy, cholecystectomy, and hernia. Concomitant active lower gastrointestinal disease (except Irritable Bowel Syndrome) or distortion of intestinal anatomy. Bleeding hemorrhoids at the time of enrollment. Acute diverticulitis at the time of enrollment. Acute or chronic pancreatitis at the time of enrollment. Unmanaged celiac disease at the time of enrollment. Positive stool test for enteric pathogens, Clostridium difficile, or presence of ova and parasites. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint is the proportion of subjects with clinical remission at the End of Treatment Visit (Visit 9). Clinical remission is defined as the Modified Mayo Total Score of 0 to 2, with, stool frequency sub-score of 0 or 1 (minimum 1 point decrease from baseline), rectal bleeding sub-score of 0 and endoscopic sub-score of 0 or 1.
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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) |
Reduction of stool frequency defined as a reported score of 0 or 1, with at least a reduction of 1 point from baseline and absence of rectal bleeding (MMDAI sub-score of 0) defined as a reported score of 0.
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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 | 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 | 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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Adaptive design with interim analysis allowing for early termination of one or both active arms. |
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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 | 3 |
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 | 31 |
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 |
Hong Kong |
India |
Philippines |
Russian Federation |
Ukraine |
United States |
Germany |
Italy |
Poland |
Romania |
Spain |
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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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Cristcot anticipates that the end of the trial will be the last visit of the last subject (LVLS); however, Cristcot has also incorporated into this study two interim analyses for efficacy at approximately 60% and 75% of the randomized subjects have reached their primary analysis endpoint.
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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 | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |