A study using a new drug (GED-0301) to investigate if the new drug works and is safe in subjects suffering ulcerative colitis.

• Register: EUCTR
• Last refreshed on: 2 October 2017
• Main ID: EUCTR2015-003364-36-HU
• Date of registration: 02/12/2015
• Prospective Registration: Yes
• Primary sponsor: Celgene Corporation
• Public title: A study using a new drug (GED-0301) to investigate if the new drug works and is safe in subjects suffering ulcerative colitis.
• Scientific title: A Phase 2, Open-label, Multicenter Study to Explore the Efficacy and Safety of Mongersen (GED-0301) in Subjects with Active Ulcerative Colitis.
• Date of first enrolment: 09/02/2016
• Target sample size: 40
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-003364-36
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• 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, Hungary, Poland, Slovakia, United States

Contacts

• Name: ClinicalTrialDisclosure
• Affiliation: Celgene Corporation

• Name: ClinicalTrialDisclosure
• Affiliation: Celgene Corporation

Key inclusion & exclusion criteria

Inclusion criteria:
1. Subject is = 18 years of age at the time of signing the ICF.
2. Subject is able to understand and voluntarily sign an ICF prior to conducting any studyrelated assessments/procedures.
3. Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
4. Subject must have a diagnosis of UC with a duration of at least 3 months prior to screening.
5. Subject must have moderate to severe UC, defined as MMS = 4 to = 9 with RBS = 1 at screening.
6. Subject must have a Mayo endoscopic subscore = 2 at screening.
7. Subject must have failed or experienced intolerance to at least one of the following: aminosalicylates; budesonide; systemic corticosteroids; immunosuppressants (eg, 6-mercaptopurine [6-MP], or azathioprine [AZA], or TNF-a blockers (eg, infliximab, adalimumab, or golimumab).
8. Subject must meet the following laboratory criteria:
a. White blood cell count = 3000/mm3 (= 3.0 X 10 9/L)
b. Platelet count = 100,000/mm3 (= 100 X 10 9/L)
c. Serum creatinine = 1.5 mg/dL (= 132.6 µmol/L)
d. Aspartate transaminase (AST/serum glutamic oxaloacetic transaminase [SGOT])
and alanine transaminase (ALT/serum pyruvic transaminase [SGPT]) = 2.5 X upper limit of normal (ULN)
e. Total bilirubin = 2 mg/dL (= 34 µmol/L) unless there is a confirmed diagnosis of Gilbert's disease
f. Hemoglobin = 9 g/dL (= 5.6 mmol/L)
g. Activated partial thromboplastin time (APTT) = 1.5 X ULN
9. Females of childbearing potential (FCBP1) must have a negative pregnancy test at the Screening and Baseline Visits. 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 described below:
Option 1: Any one of the following highly effective methods: hormonal contraception (oral, injection, implant, transdermal patch, vaginal ring); intrauterine device (IUD); tubal ligation; or partner’s vasectomy;
OR
Option 2: Male or female condom PLUS 1 additional barrier method: (a) diaphragm
with spermicide; (b) cervical cap with spermicide; or (c) contraceptive sponge with spermicide.
10. Male subjects (including those who have had a vasectomy) when engaging in sexual activity with females who are able to become pregnant must use barrier contraception (male latex condom or nonlatex condom NOT made out of natural [animal] membrane [for example, polyurethane]) while on IP and for at least 28 days after the last dose.
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 36
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 4

Exclusion criteria:
1. Subject has a diagnosis of CD, indeterminate colitis, ischemic colitis, microscopic colitis, radiation colitis or diverticular disease-associated colitis.
2. Subject has ulcerative colitis restricted to distal 15 cm or less (eg, ulcerative proctitis).
3. Subject had surgery as a treatment for UC or who, in the opinion of the Investigator, is likely to require surgery for UC during the study.
4. Subject has clinical signs suggestive of fulminant colitis or toxic megacolon.
5. Subject is stool positive for any enteric pathogen or Clostridium difficile (C. difficile) toxin at screening.
6. Subject has history of colorectal cancer or colorectal dysplasia.
7. Prior treatment with more than 2 TNF-a blockers (eg, infliximab, adalimumab, or golimumab).
8. Prior treatment with any integrin antagonists (eg, natalizumab or vedolizumab).
9. Use of TNF-a blockers within 8 weeks of the screening.
10. Subject had prior treatment with mycophenolic acid, tacrolimus, sirolimus, cyclosporine, thalidomide or apheresis (eg, Adacolumn®) for the treatment of UC. In addition, prior use of any of these treatment modalities for an indication other than UC within 8 weeks of screening is also excluded.
11. Subject has received intravenous (IV) corticosteroids within 2 weeks of screening.
12. Subject has received topical treatment with 5-ASA or corticosteroid enemas or suppositories within 2 weeks of screening.
13. Subject has received total parenteral nutrition (TPN) within 4 weeks of screening.
14. Subject has a history of any clinically significant neurological, renal, hepatic, gastrointestinal, pulmonary, metabolic, cardiovascular, psychiatric, endocrine, hematological disorder or disease, or any other medical condition that, in the investigator's opinion, would prevent the subject from participation in the study.
15. Subject has 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.
16. Subject is pregnant or breastfeeding.
17. Subject has a 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.
18. Subject has a known active current or history of medically important recurrent bacterial, viral, fungal, mycobacterial or other infections (including but not limited to tuberculosis and 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.
19. Subject has a history of congenital or acquired immunodeficiency (eg, common variable immunodeficiency disease).
20. Subject has a 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 or carcinoma in situ of the cervix with no evidence of recurrence within the previous 5 years
21. Subject has received investigational drug or device within 1

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

Health Condition(s) or Problem(s) studied

Ulcerative Colitis.
MedDRA version: 18.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856

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

Intervention(s)

Product Name: Mongersen
Product Code: GED-0301
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Mongersen
CAS Number: 1443994-86-6
Current Sponsor code: GED-0301
Other descriptive name: GED-0301
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-

Primary Outcome(s)

Main Objective: To explore the effect of GED-0301 on clinical activity, as measured by the MMS in subjects with active UC.

Timepoint(s) of evaluation of this end point: Week 8.

Primary end point(s): Efficacy:
The proportion of subjects achieving clinical remission in the MMS, defined as a MMS of = 2, with no individual subscore > 1.

Secondary Objective: 1. To explore the effect of GED-0301 on endoscopic outcome, as measured by the Mayo endoscopic subscore, in subjects with active UC.
2. To evaluate the safety and tolerability of GED-0301 in subjects with active UC.

Secondary Outcome(s)

Secondary end point(s): Efficacy:
1. The proportion of subjects achieving a MMS of = 2, with rectal bleeding subscore of 0 and stool frequency subscore and Mayo endoscopic subscore = 1.
2. The proportion of subjects achieving a Mayo endoscopic subscore = 1.
3. The proportion of subjects achieving a Mayo endoscopic subscore by individual segment (rectum, sigmoid, descending colon, transverse colon, ascending colon/cecum) = 1.
4. The proportion of subjects achieving clinical response in the MMS, defined as a decrease from baseline 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 = 1.
5. The proportion of subjects achieving endoscopic response, defined as a decrease from baseline of at least 1 point in the Mayo endoscopic subscore.
6. The proportion of subjects achieving clinical remission in the TMS, defined as a TMS of = 2, with no individual subscore > 1.
7. The proportion of subjects achieving clinical response in the TMS, defined as a decrease from baseline in the TMS of at least 3 points and at least 30%, along with a reduction in the RBS of at least 1 point or an absolute RBS of = 1.
Safety:
The evaluation of safety and tolerability of GED-0301, assessed by the type, frequency and severity of adverse events, and its relationship to IP, discontinuation due to adverse events, and clinically significant changes in vital signs, ECGs, and/or laboratory findings.

Timepoint(s) of evaluation of this end point: Efficacy: Week 8.
Safety: Through Week 52.

Secondary ID(s)

GED-0301-UC-002

Source(s) of Monetary Support

Celgene Corporation