E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute Ulcerative Colitis (UC) |
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E.1.1.1 | Medical condition in easily understood language |
Acute Ulcerative Colitis (UC) |
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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 | 19.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045365 |
E.1.2 | Term | Ulcerative colitis |
E.1.2 | System Organ Class | 100000004856 |
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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 |
Primary:
• To prove the superiority of a 12-week add-on treatment with 3.2 g/day gastro-resistant phosphatidylcholine granules (LT-02) in at least one of two different dosing regimens versus LT-02 placebo for the induction of remission in patients with ulcerative colitis (UC) refractory to standard
treatment with mesalamine. |
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E.2.2 | Secondary objectives of the trial |
Secondary:
• To study safety and tolerability in the form of adverse events (AEs) and laboratory parameters,
• To compare two different dosing regimens of LT-02,
• To assess patients’ quality of life. |
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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 |
Open-label sub-study (PCG-5/OLT):
• To induce remission of UC in patients not in remission at week 12 or in patients who were prematurely withdrawn ≥ 8 weeks after randomization due to lack of efficacy without showing clinical response. |
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E.3 | Principal inclusion criteria |
Principle Inclusion criteria:
- Men or women, 18 to 70 years of age,
- Established diagnosis of UC, based on clinical history, exclusion of infectious causes, and characteristic endoscopic and histologic findings,
- Active UC with disease extent ≥ 15 cm (proctitis only patients to be excluded), confirmed by endoscopy and histology,
- Mesalamine (5-ASA) refractory disease,
- Elevated stool calprotectin at screening.
Inclusion criteria for open-label sub-study:
The following inclusion criterion will apply only to the open label sub-study:
1. Patients not in remission of UC at week 12, or patients withdrawn ≥ 8 weeks after randomization due to lack of efficacy and
showing no clinical improvement. |
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E.4 | Principal exclusion criteria |
Principle Exclusion criteria:
- Crohn's disease, indeterminate colitis, ischemic colitis, radiation colitis, microscopic colitis (i.e., collagenous colitis and lymphocytic colitis),
diverticular disease associated colitis,
- Colon resection,
- Evidence of infectious colitis (e.g., pathogenic bacteria or Clostridium difficile toxin in stool culture at screening),
- Other inflammatory or bleeding disorders of the colon and intestine, or diseases that may cause diarrhea or gastrointestinal bleeding,
- History or presence of ischemic heart disease, myocardial infarction, peripheral arterial disease, ischemic stroke, or transient ischemic attack,
- Treatment with steroids (oral, inhalative, or intravenous [IV]), cyclosporine or tacrolimus within last 4 weeks prior to randomization,
- Treatment with methotrexate within last 6 weeks prior to randomization,
- Treatment with TNF-alpha-antagonists, azathioprine, 6-mercaptopurine, or anti-integrin therapy within last 8 weeks prior to randomization,
- Treatment with rectal corticosteroid formulation within last 2 weeks prior to randomization,
- Concomitant treatment with coumarins (e.g., phenprocoumon),
- Existing or intended pregnancy or breast-feeding.
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E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of patients in remission |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
after week 12 (LOCF) of double-blind treatment phase |
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E.5.2 | Secondary end point(s) |
Double-blind (12-week) and optional open-label (12-week) phase:
• Percentage of patients with clinical improvement,
• Times to first resolution of clinical symptoms,
• Number of stools per week,
• Number of bloody stools per week,
• Number of days with urgency per week,
• Percentage of patients with mucosal healing,
• Percentage of patients with histologic remission,
• Patients quality of life,
Open-label phase (only):
• Percentage of patients in remission at end of OL phase. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
after week 12 (LOCF) of double-blind and/or open-label treatment phase |
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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 | No |
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 | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
To evaluate two different dosing regimens (twice daily and four-times daily) of LT-02 versus placebo. |
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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 | Yes |
E.8.1.7.1 | Other trial design description |
Due to different dosing regimens, a double-dummy design will be used. |
|
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 | 44 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 95 |
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 |
Austria |
Belgium |
Czech Republic |
Germany |
Hungary |
Israel |
Latvia |
Lithuania |
Netherlands |
Poland |
Russian Federation |
Slovakia |
Switzerland |
Ukraine |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
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 | 6 |