An Efficacy and Safety Study of Mongersen (GED-0301) in Subjects With Active Ulcerative Colitis
Condition: Colitis, Ulcerative
MeSH terms: Colitis; Colitis, Ulcerative; Ulcer
Intervention: GED-0301
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 41.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Ulcerative Colitis; GED-0301; Mongersen; Efficacy; Safety

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.
    

Eligibility 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.