EFFICACY AND SAFETY STUDY OF GED-0507-34-LEVO (GED0507) FOR TREATMENT OF PATIENTS WITH ACTIVE ULCERATIVE COLITIS

• Register: EUCTR
• Last refreshed on: 21 August 2017
• Main ID: EUCTR2016-001684-36-HU
• Date of registration: 10/08/2016
• Prospective Registration: Yes
• Primary sponsor: PPM SERVICES SA
• Public title: EFFICACY AND SAFETY STUDY OF GED-0507-34-LEVO (GED0507) FOR TREATMENT OF PATIENTS WITH ACTIVE ULCERATIVE COLITIS
• Scientific title: A PHASE 2, RANDOMIZED, PLACEBO-CONTROLLED, MULTICENTER STUDY TO INVESTIGATE THE EFFICACY AND SAFETY OF GED-0507-34-LEVO (GED0507) FOR TREATMENT OF SUBJECTS WITH ACTIVE ULCERATIVE COLITIS
• Date of first enrolment: 19/10/2016
• Target sample size: 207
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-001684-36
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Bulgaria, Canada, Czech Republic, France, Hungary, Italy, Latvia, Poland, Slovakia, Spain, Ukraine, United Kingdom, United States

Contacts

• Name: Daniel Szabo, MD
• Affiliation: Quintiles

• Name: Daniel Szabo, MD
• Affiliation: Quintiles

Key inclusion & exclusion criteria

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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 196
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 11

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 s

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Ulcerative Colitis
MedDRA version: 20.0 Level: LLT Classification code 10021184 Term: IBD System Organ Class: 10017947 - Gastrointestinal disorders
MedDRA version: 20.0 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 10017947 - Gastrointestinal disorders
MedDRA version: 20.0 Level: LLT Classification code 10045366 Term: Ulcerative colitis, unspecified System Organ Class: 10017947 - Gastrointestinal disorders
MedDRA version: 20.0 Level: SOC Classification code 10017947 Term: Gastrointestinal disorders System Organ Class: 10017947 - Gastrointestinal disorders

Intervention(s)

Product Name: GED-0507-34-Levo
Product Code: GED0507
Pharmaceutical Form: Gastro-resistant tablet
INN or Proposed INN: (S)-(-)-3-(4-Aminophenyl)-2-methoxypropionic Acid
Current Sponsor code: GED-0507-34-Levo
Other descriptive name: GED-0507-34-LEVO
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 80-
Pharmaceutical form of the placebo: Gastro-resistant tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: 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.

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

Timepoint(s) of evaluation of this end point: week 8

Secondary Objective: 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.

Secondary Outcome(s)

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

Timepoint(s) of evaluation of this end point: week 8

Secondary ID(s)

GED0507-UC-001

2016-001684-36-SK

Source(s) of Monetary Support

PPM Services SA