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 | 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 |
The primary objective will be to assess the efficacy of LYC-30937-EC in inducing remission compared with placebo in subjects with active UC over a treatment duration of 8 weeks. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives will be to evaluate the safety, tolerability, plasma tissue PK of LYC-30937-EC compared with placebo in subjects with active UC. |
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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 |
Two pharmacokinetic sub studies will be part of the research: the safety pharmacokinetic substudy and the serial pharmacokinetic substudy. If patients agree to participate in one of these studies, extra blood will be taken to 1) determine plasma concentrations of LYC-30937, and 2) assess plasma PK parameters of LYC-30937 and its metabolite. |
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E.3 | Principal inclusion criteria |
1. Consenting adults aged 18–75 years. 2. Have had UC diagnosed at least 6 months prior to screening and with a minimum disease extent of ≥ 15 cm from the anal verge. The diagnosis of UC must be confirmed by endoscopic and histologic evidence (histology may be confirmed at screening based on biopsy collection during the screening colonoscopy with histological evaluation done by the site). 3. Have active UC defined as a TMS of 4–11 (inclusive) with endoscopic subscore of ≥ 2 and rectal bleeding subscore of ≥ 1 at screening. 4. Male and female subjects of childbearing potential must agree to use adequate birth control measures during the study. Female subjects of child bearing potential must use two highly effective forms of contraception, unless surgically sterilized, partner has had a vasectomy, or they will be abstinent, during study participation and for 30 days after their last dose of study drug. Highly effective methods of birth control in this study include: intrauterine device, hormonal contraceptives (oral, patch, long acting injectable, implant), double-barrier method (condom or diaphragm with spermicide). (Post-menopausal defined as lack of menses for ≥ 6 months prior to screening confirmed with serum FSH > 25 mIU/mL at screening.) 5. Must be currently receiving treatment with at least one of the following therapies (subjects need to be receiving medications consistent with standard of care and stable doses of medications need to be established prior to screening): a. Oral aminosalicylates (eg, mesalamine, sulfasalazine, olsalazine, balsalazide) for ≥ 6 weeks with the dose stable for ≥ 3 weeks prior to the Screening endoscopy. b. Prednisone (dose ≤ 20 mg daily) or equivalent for ≥ 4 weeks and receiving a stable dose for ≥ 2 weeks prior to the screening endoscopy. 6. If oral aminosalicylates (ASA) or corticosteroids have been recently discontinued, they must have been stopped for ≥ 2 weeks prior to the screening endoscopy (eg, if recently tapered off coricosteroid). 7. Ability to provide written informed consent and to be compliant with the schedule of events |
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E.4 | Principal exclusion criteria |
1. Known mitochondrial disorder. 2. History of CD or indeterminate colitis or the presence or history of a fistula consistent with CD. 3. History of bleeding disorders (eg, complement disorders, hemophilia, history of uncontrolled bleeding). 4. Severe extensive disease that in physician judgment the subject is likely to require colonic surgery during the 8 week double-blind course (eg, fulminant colitis, toxic megacolon, bowel perforation, evidence of an acute abdomen). 5. Positive test for Clostridium (C.) difficile, positive stool culture for enteric pathogens (eg, Salmonella, Shigella, Campylobacter), or presence of ova or parasites at screening. Note that C. difficile may be treated and the subject may be retested for screening after he/she completed this treatment. 6. Any of the following laboratory abnormalities: a. liver function tests > 1.5 x the upper limit of normal (ULN) or direct bilirubin > 1.5 x ULN. b. hemoglobin < 8.5 g/dl (international system units [SI]: < 85 g/L). c. neutrophils < 1500/mm3 (SI: < 1.5 x 109/L). d. white blood cell (WBC) count < 3,000/mm3 (SI: < 3.0 x 109/L). e. Platelets < 80,000 mm3 (SI: 80 x 109/L). f. international normalized ratio (INR) > 1.5. g. serum creatinine > 1.4 mg/dL for women or > 1.6 mg/dL for men. 7. Have had treatment with immunosuppressant agents (eg, cyclosporine, azathioprine, mercaptopurine, methotrexate, tacrolimus, sirolimus, or mycophenolate mofetil (MMF) within 8 weeks prior to initiation of screening procedures. 8. Pregnancy, lactation, or a positive serum beta human chorionic gonadotropin (hCG) at screening. Female subjects should not be planning to become pregnant while enrolled in the trial. 9. Clinically relevant hepatic, neurological, pulmonary, ophthalmological, gastrointestinal, endocrine, psychiatric, or other major systemic disease making implementation of the protocol or interpretation of the study difficult or that would put the subject at risk by participating in the study. 10. History of uveitis within the 12 months prior to initiation of screening procedures. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The proportion of subjects who achieve a clinical remission at Week 8 using the modified Mayo score (MMS). Clinical remission is defined as Mayo stool frequency subscore of ≤1, Mayo rectal bleeding subscore of 0 and Mayo endoscopy subscore of ≤1. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At week 8 of participation of a subject. |
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E.5.2 | Secondary end point(s) |
• The proportion of subjects who achieve clinical remission at Week 8 using the total Mayo score (TMS), defined as a Mayo score of ≤2, with no individual score >1, and rectal bleeding score of 0; • The proportion of subjects with a clinical response at Week 8, defined as a reduction from Baseline MMS of ≥2 points and ≥25%, and a decrease from baseline in rectal bleeding subscore of ≥1 point or an absolute rectal bleeding subscore of ≤1 point; • The proportion of subjects with a clinical response at Week 8, defined as a reduction from Baseline in TMS of ≥3 points and ≥30%, and a decrease from Baseline in rectal bleeding subscore of ≥1 point or an absolute rectal bleeding subscore of ≤1 point; • The change from baseline TMS at Week 8; • The change from baseline to Week 8 in fecal calprotectin. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At week 8 of participation of a patient. |
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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 | Yes |
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 | 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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 33 |
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 |
Canada |
Czech Republic |
Hungary |
Netherlands |
Poland |
Serbia |
United States |
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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 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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
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 |