Overview

An Efficacy and Safety Study of Mongersen (GED-0301) in Subjects With Active Ulcerative Colitis

Status:
Completed
Trial end date:
2017-08-08
Target enrollment:
0
Participant gender:
All
Summary
This is a phase 2, open-label, multicenter study to explore the efficacy and safety of oral GED- 0301 in subjects with active UC, defined as a modified Mayo score (MMS) ≥ 4 and ≤ 9 and a Mayo endoscopic subscore≥ 2. Approximately 40 subjects will be enrolled using an Interactive Voice Response System (IVRS) or an Interactive Web Response System (IWRS) to receive open-label, oral GED-0301 160 mg for duration of 52 week treatment. Enrollment of subjects with previous exposure to TNF-α blockers will be limited to approximately 15 subjects. The number of subjects with extensive colitis is targeted to comprise approximately 50% of the entire study population.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Celgene
Celgene Corporation
Criteria
Inclusion Criteria:

Inclusion Criteria:

- Subjects must satisfy the following criteria to be enrolled in the study:

1. Subject is ≥ 18 years of age at the time of signing the informed consent form
(ICF).

2. Subject is able to understand and voluntarily sign an informed consent form
(ICF)prior to conducting any study related assessments/procedures.

3. Subject is willing and able to adhere to the study visit schedule and other
protocol requirements.

4. Subject must have diagnosis of Ulcerative Colitis (UC) with a duration of at
least 3 months prior to screening.

5. Subject must have moderate to severe Ulcerative Colitis (UC), defined as Modified
Mayo score (MMS) ≥ 4 to ≤ 9 with rectal bleeding subscore (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 Tumor necrosis factor
(TNF)-α blockers (eg, infliximab, adalimumab, or golimumab)

8. Subject must meet the following laboratory criteria:

1. White blood cell count ≥ 3000/mm3 (≥ 3.0 X 109/L)

2. Platelet count ≥ 100,000/mm3 (≥ 100 X 109/L)

3. Serum creatinine ≤ 1.5 mg/dL (≤ 132.6 μmol/L)

4. Aspartate transaminase (AST/serum glutamic oxaloacetic transaminase (SGOT))
and alanine transaminase (ALT/serum pyruvic transaminase (SGPT)2.5 X upper
limit of normal (ULN)

5. Total bilirubin ≤ 2 mg/dL (≤ 34 μmol/L) unless there is a confirmed
diagnosis of Gilbert's disease

6. Hemoglobin ≥ 9 g/dL (≥ 5.6 mmol/L)

7. Activated partial thromboplastin time (APTT) 1.5 X ULN

9. Females of childbearing potential (FCBP) must have a negative pregnancy test at
the Screening and Baseline Visits. While on Investigational Product (IP)and for
at least 28 days after taking the last dose of Investigational Product (IP),
females of childbearing potential (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 Investigational Product
(IP) and for at least 28 days after the last dose.

Exclusion Criteria:

- The presence of any of the following will exclude a subject from enrollment:

1. Subject has a diagnosis of Crohn's Disease (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 ulcerative colitis (UC)or who, in the
opinion of the Investigator, is likely to require surgery for ulcerative colitis
(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 Tumor necrosis factor (TNF)-α blockers (eg,
infliximab, adalimumab, or golimumab).

8. Prior treatment with any integrin antagonists (eg, natalizumab or vedolizumab).

9. Use of Tumor necrosis factor (TNF)-α 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
ulcerative colitis (UC). In addition, prior use of any of these treatment
modalities for an indication other than ulcerative colitis (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 aminosalicylic acid (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 intravenous (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:

1. Treated (ie, cured) basal cell or squamous cell in situ skin carcinomas

2. 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 month of screening.

22. Subject has a history of alcohol, drug, or chemical abuse within the 6 months
prior to screening.

23. Subject has a known hypersensitivity to oligonucleotides or any ingredient in the
Investigational Product (IP).

24. Subject has prior treatment with GED-0301 or participated in a clinical study
involving GED-0301.