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 | LLT |
E.1.2 | Classification code | 10021184 |
E.1.2 | Term | IBD |
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 | 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 | LLT |
E.1.2 | Classification code | 10045366 |
E.1.2 | Term | Ulcerative colitis, unspecified |
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 | SOC |
E.1.2 | Classification code | 10017947 |
E.1.2 | Term | Gastrointestinal disorders |
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 |
The primary objective of the study is to evaluate the clinical efficacy of GED-0507-34-Levo (80 mg BID and 160 mg BID), compared with placebo, in subjects with active UC. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective of the study is to evaluate the safety and tolerability of GED-0507-34-Levo (80 mg BID and 160 mg BID), 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 |
A PK sub-study will be conducted at selected sites to evaluate the PK profile of GED-0507-34-Levo (parent compound) and N-Acetyl-GED-0507-34-Levo (metabolite) in subjects with active UC and to explore the relationship between GED-0507-34-Levo PK exposures and key efficacy endpoints. The target for the PK sub-study is to achieve participation of approximately 50% of the randomized subjects. A separate consent will be signed for this assessment at the Screening Visit. |
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E.3 | Principal inclusion criteria |
Subjects must satisfy the following criteria to be enrolled in the study:
1. Male or female aged 18 and over at the time of signing the informed consent.
2. Must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
3. Must be able to adhere to the study visit schedule and other protocol requirements.
4. Diagnosis of UC with a duration of at least 3 months prior to the Screening Visit.
5. MMS ≥ 4 to ≤ 8 (range: 0 - 9) prior to randomization in the study
• SFS ≥ 1 and RBS = 1 or 2
• Mayo endoscopic sub-score > 1 and < 3 prior to randomization in the study
6. Subjects are required to have a colonoscopy if one has not been performed within 12 months prior to the Screening Visit.
7. Subjects who have relapsed on maintenance therapy with doses of 5-ASA ≤ 2.4 g/day.
8. Must meet the following laboratory criteria:
• WBC count ≥ 3000/mm3 and < 14,000/mm3
• Platelet count ≥ 100,000/mm3
• Serum creatinine ≤ 1.5 mg/dL (≤ 132.6 μmol/L)
• AST (SGOT) and ALT (SGPT) ≤ 2 upper limit of normal (ULN). If initial test shows ALT or AST > 2 ULN, 1 repeat test is allowed during the screening period
• Total bilirubin ≤ 2 mg/dL (≤ 34 mol/L) and albumin > lower limit of normal (LLN). If initial albumin test result is < 2 g/dL, 1 repeat test is allowed during the screening period
• Hemoglobin ≥ 9 g/dL (≥ 5.6 mmol/L)
9. FCBP must have a negative pregnancy test at screening and the Baseline Visit. While on IP and for at least 28 days after taking the last dose of IP, FCBP who engage in activity in which conception is possible must use one of the approved contraceptive options
10. Male subjects (including those who have had a vasectomy) who engage in activity in which conception is possible must use barrier contraception while on investigational product and for at least 28 days after the last dose of investigational product. |
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E.4 | Principal exclusion criteria |
The presence of any of the following will exclude a subject from enrollment:
1. Diagnosis of Crohn's disease, indeterminate colitis, ischemic colitis, microscopic colitis, radiation colitis, or diverticular disease-associated colitis.
2. UC restricted to the distal 15 cm or less (eg, ulcerative proctitis).
3. Subjects who have had surgery as a treatment for UC or who, in the opinion of the Investigator, are likely to require surgery for UC during the study.
4. Clinical signs suggestive of fulminant colitis or toxic megacolon.
5. Evidence of pathogenic enteric infection.
6. History of colorectal cancer or colorectal dysplasia.
7. Prior use of any TNF inhibitor (or any biologic agent).
8. Prior use of mycophenolic acid, tacrolimus, sirolimus, cyclosporine, or thalidomide.
9. Subjects who have relapsed on maintenance therapy with doses of 5-ASA > 2.4 g/day will be excluded from the study. If a subject had a recent 5-ASA dose reduction from > 2.4g/day to ≤ 2.4 g/day and relapsed within 2 weeks of that dose reduction.
10. Oral aminosalicylates are not permitted during the study treatment period (from visit 2 until visit 7 or ET visit).
11. Use of budesonide-MMx within the last 8 weeks.
12. Use of oral and/or IV corticosteroids within 2 weeks of the Screening Visit.
13. Use of immunosuppressants (azathioprene [AZA], 6-mercaptopurine [6-MP] or methotrexate [MTX]) within 8 weeks of the Screening Visit.
14. Use of topical treatment with 5-ASA or corticosteroid enemas or suppositories within 2 weeks of the Screening Visit.
15. History of any clinically significant neurological, renal, hepatic, GI, pulmonary, metabolic, cardiovascular, psychiatric, endocrine, hematological disorder or disease or any other medical condition that, in the Investigator's opinion, would preclude participation in the study.
16. Prior history of suicide attempt at any time in the subject’s lifetime prior to randomization in the study or major psychiatric illness requiring hospitalization within 3 years of study randomization.
17. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she was to participate in the study or confounds the ability to interpret data from the study.
18. Pregnant or breast feeding.
19. History of any of the following cardiac conditions within 6 months of screening: myocardial infarction, acute coronary syndrome, unstable angina, new onset atrial fibrillation, new onset atrial flutter, second- or third-degree atrioventricular block, ventricular fibrillation, ventricular tachycardia, heart failure, cardiac surgery, interventional cardiac catheterization (with or without a stent placement), interventional electrophysiology procedure, or presence of implanted defibrillator.
20. Known active current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infections (including but not limited to tuberculosis, atypical mycobacterial disease, and herpes zoster), human immunodeficiency virus (HIV), or any major episode of infection requiring hospitalization or treatment with IV or oral antibiotics within 4 weeks of screening.
21. Subjects with active hepatitis B infection, as described in Appendix D of the protocol, are ineligible for the study. Subjects without current hepatitis B infection, as described in Appendix E of the protocol, may participate in the study.
22. Subjects who are positive for the hepatitis C antibody are not eligible for the study.
23. History of congenital or acquired immunodeficiency (eg, Common Variable Immunodeficiency Disease).
24. History of malignancy, except for:
a. Treated (ie, cured) basal cell or squamous cell in situ skin carcinomas
b. Treated (ie, cured) cervical intraepithelial neoplasia (CIN) or carcinoma in situ of the cervix with no evidence of recurrence within the previous 5 years
25. Any condition that could affect oral drug absorption, including gastric resections, gastroparesis, or bariatric surgery, such as gastric bypass.
26. Subjects who have received any investigational drug or device within 3 months of study randomization.
27. History of alcohol, drug, or chemical abuse within the 6 months prior to screening.
28. Known hypersensitivity to GED-0507-34-Levo or any excipients in the formulation. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of this study is the proportion of subjects achieving a clinical remission in the Modified Mayo score (MMS) at Week 8, defined as an MMS of ≤ 2, with individual sub-scores (stool frequency [SF] and Endoscopy) ≤ 1 and Rectal Bleeding sub-score (RBS) = 0 |
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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 secondary efficacy endpoints are the following:
• The proportion of subjects achieving clinical response at Week 8, defined as a decrease from baseline in the MMS of at least 2 points and at least 25%, along with a reduction in the RBS of at least 1 point or an absolute RBS of ≤ 1
• The proportion of subjects achieving endoscopic remission at Week 8, defined as a Mayo endoscopic sub-score = 0
• The proportion of subjects achieving endoscopic response at Week 8, defined as a decrease from baseline of at least 1 point in the Mayo endoscopic sub-score
• The proportion of subjects achieving an RBS ≤ 1 at Week 8
Secondary Safety Endpoints
• Type, frequency, severity, and relationship of AEs to investigational product (IP)
• Number of subjects who discontinue IP due to any AE
• Frequency of clinically significant changes in vital signs and/or laboratory findings |
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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 | Yes |
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.8.2.4 | 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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 71 |
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 |
Bulgaria |
Canada |
Czech Republic |
France |
Hungary |
Italy |
Latvia |
Poland |
Slovakia |
Spain |
Ukraine |
United Kingdom |
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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The End of Trial is defined as either the date of the last visit of the last subject to complete the study or the date of receipt of the last data point from the last subject that is required for primary, secondary, and/or exploratory analysis, as pre-specified in the protocol and/or the Statistical Analysis Plan (SAP), whichever is the later date. |
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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 | 1 |
E.8.9.1 | In the Member State concerned days | 18 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial days | 18 |