| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Patients with ulcerative colitis (UC) according to European Crohn's and Colitis Organisation (ECCO) consensus; Simple Clinical Colitis Activity Index (SCCAI) ≥5 and SCCAI subscore for “blood in stool” ≥2 at Baseline Visit. |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10045365 |
| E.1.2 | Term | Ulcerative colitis |
|
| 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 of this study is to assess the efficacy and safety of modified-release PC (LT-02) in mesalazine-refractory UC. |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objective is to determine the optimal dose of modified-release PC
(LT-02) in mesalazine-refractory UC. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1) Men and women ≥18 years who have given written Informed Consent,
2) Patients with proven UC (according to ECCO consensus definition [24]:
UC is a chronic continuous mucosal inflammation of the colon without
granulomas on biopsy, affecting the rectum and variable extent of the colon
in continuity, which is characterized by a relapsing and remitting course. The
diagnoses should be established by a combination of medical history, clinical
evalution, and typical endoscopic and histologic findings:
a) Medical history and clinical features: loose stools [>6 weeks], episodes of
bloody stools and stool urgency, episodes of relapse and periods of
remission or an unremitting, continuous course over months; exclusion of
infectious colitis [microbiological testing, including Clostridium difficile toxin A
and B, Campylobacter spp., E. coli 0157:H7; depending on the medical
history fresh, warm stool samples should be tested for amoebae or other
parasites], exclusion of drug-induced forms of colitis,
b) Endoscopic features, including a colonoscopy with intubation of the
terminal ileum: inflammation of the rectum, continuous inflammation to more
proximal parts, usually clear demarcation between inflamed and normal
areas. Signs of inflammation are vascular congestion or reduction of visible
vascular patterns, as well as mucosal friability [after contact with the
endoscope]. Moreover, a coarse granular appearance, mucosal erosions or
ulcerations may occur,
c) Histologic features from multiple mucosal biopsies: absence of
granulomas, architectural features [crypt branching, crypt distortion, crypt
atrophy or surface irregularity], epithelial cell abnormalities [mucin depletion,
Paneth cell metaplasia] and inflammatory signs [increased lamina propria
cellularity, basal plasmacytosis, basal lymphoid aggregates, lamina propria
eosinophils],
Patients may be included into the study if clinician, endoscopist [may be
identical with clinician] and pathologist state that the found features are
compatible with the diagnosis of UC),
3) Patients naïve to any form of controlled release PC treatment,
4) Active disease course for the last 6 weeks or longer with bloody diarrhea
(anamnestic mean number of bloody stool per day ≥4),
5) SCCAI ≥5 and SCCAI subscore for “blood in stool” ≥2 at Baseline Visit (V2),
(SCCAI and subscore for blood are calculated as the rounded mean over the
last 7 days),
6) Patients with an inadequate response to a treatment with ≥3g of mesalazine
per day, over a period of 4 weeks or a documented intolerance to
mesalazine,
7) Other drugs for the treatment of UC are allowed, under the following
circumstances:
- Systemic acting oral steroids are allowed if taken for ≥8 weeks prior to start
of the study with a stable dose for ≥4 weeks prior to start of the study,
- Immunosuppressive therapy with azathioprine (2-2.5 mg/kg) or 6-
mercaptopurine (1-1.5 mg/kg) is allowed, if taken for ≥3 months prior to
start of the study,
8) Ability of the patient to understand character and individual consequences of
the clinical study,
9) Special requirements for women of childbearing potential:
- Negative pregnancy test at V1 and V2,
- Use of one highly effective method of contraception for the entire duration
of the study, defined as those which result in a low failure rate (i.e. less
than 1% per year) when used constantly and correctly such as hormonal
contraception, intrauterine contraceptive device or combination of two
barrier methods (e.g. condom or diaphragm plus spermicidal cream),
- Efficacy of hormonal contraception has to be ensured by following the
manufacturers’ recommendations outlined in the respective package insert,
especially for cases of diarrhea and vomiting,
10) Drugs applied for the treatment of UC have to be on a stable dosage for at
least 4 weeks. Patients cannot be included into the study if the treatment of
UC was discontinued within the last 4 weeks prior to the study. |
|
| E.4 | Principal exclusion criteria |
1) Toxic megacolon or fulminant colitis,
2) a) Therapy with cyclosporine, tacrolimus, methotrexate, or tumor necrosis-
(TNF)-alpha-antagonists within 3 months prior to study entry,
b) Current treatment with opiates or loperamide,
c) Current antibiotic treatment,
3) Rectal applications of aminosalicylates, budesonide, or other steroids within
4 weeks prior to study entry,
4) Oral application of topically acting steroids, e.g. budesonide, within 4 weeks
prior to study start,
5) Treatment with other IMP within 3 months prior to study entry,
6) Condition after complete or partial resection of the colon,
7) Infectious colitis, including cytomegalovirus or Clostridium difficile induced
colitis,
8) Crohn’s disease,
9) Colitis due to other reasons than UC like known diverticulitis, radiation colitis,
ischemic colitis, microscopic colitis, or indeterminate colitis,
10) Malabsorption syndromes, chronic pancreatitis,
11) Celiac disease,
12) Acute bleeding hemorrhoids,
13) Other inflammatory or bleeding disorders of the gastrointestinal tract, or
diseases that may cause diarrhea or gastrointestinal bleeding,
14) Pregnant or nursing women,
15) Known drug, alcohol, or medication abuse during the last 2 years prior to
start of the study,
16) Any other uncontrolled systemic diseases (e.g. cardiac, renal, pulmonary, or
hepatic) or severe chronic diseases (e.g. malignant tumor, HIV infection,
high-grade intraepithelial neoplasia),
17) Ulcerative proctitis with a disease extent <10 cm,
18) Participation in another clinical trial within the last 30 days, simultaneous
participation in another clinical trial, or previous participation in this trial.
For all patients included in Lithuania, the following criterion is added as exclusion
criterion no. 2:
“No current treatment for UC with either high-dose 5-ASA (at least 3g/d) or oral
steroids or immunosuppressants or combinations.”
Please note that due to this insertion, the numbering of the subsequent exclusion
criteria is shifted in Lithuania (i.e. former criterion no. 2 is changed to no. 3, former
no. 3 is changed to no. 4 etc.). |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Mean rounded SCCAI change from baseline (V2) to Week 12 (V5) or last assessment during the double-blind treatment period. |
|
| 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 | No |
| 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) | 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 | 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 | 16 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 30 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| 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
|
| last patient of the last visit |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 18 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 18 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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