Trial record 43 of 2040 for:    digestive | Open Studies | Exclude Unknown | United States

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2016 by Celgene Corporation
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT02601300
First received: November 6, 2015
Last updated: May 11, 2016
Last verified: May 2016
  Purpose

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.


Condition Intervention Phase
Colitis, Ulcerative
Drug: GED-0301
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2, Open-Label, Multicenter Study to Explore the Efficacy and Safety of MONGERSON (GED-0301) in Subjects With Active Ulcerative Colitis.

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • The proportion of subjects achieving clinical remission in the modified Mayo score (MMS), defined as a MMS of ≤ 2, with no individual subscore > 1 [ Time Frame: Up to approximately week 8 ] [ Designated as safety issue: No ]
    The MMS is based on the stool frequency subscore, rectal bleeding subscore and endoscopy subscore of the total Mayo score, and excludes the Physician's Global Assessment (PGA) subscore. The modified Mayo score ranges from 0 to 9 points


Secondary Outcome Measures:
  • The proportion of subjects achieving a modified Mayo score (MMS) of ≤ 2, with rectal bleeding subscore of 0 and stool frequency subscore and Mayo endoscopic subscore ≤ 1 [ Time Frame: Up to approximately 8 weeks ] [ Designated as safety issue: No ]
    The MMS is based on the stool frequency subscore, rectal bleeding subscore and endoscopy subscore of the total Mayo score, and excludes the Physician's Global Assessment (PGA) subscore. The modified Mayo score ranges from 0 to 9 points

  • The proportion of subjects achieving a Mayo endoscopic subscore ≤ 1 [ Time Frame: Up to approximately 8 weeks ] [ Designated as safety issue: No ]
    Mayo endoscopic subscore is one of Mayo score component and it ranges from 0 to 3 points

  • The proportion of subjects achieving a Mayo endoscopic subscore by individual segment (rectum, sigmoid, descending colon, transverse [ Time Frame: Up to approximately 8 weeks ] [ Designated as safety issue: No ]
    Mayo endoscopic subscore is one of Mayo score component and it ranges from 0 to 3 points

  • 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 rectal bleeding subscore (RBS) of at least 1 point or an absolute RBS ≤ 1 [ Time Frame: Up to approximately 8 weeks ] [ Designated as safety issue: No ]
    The MMS is based on the stool frequency subscore, rectal bleeding subscore and endoscopy subscore of the total Mayo score, and excludes the Physician's Global Assessment (PGA) subscore. The modified Mayo score ranges from 0 to 9 points

  • The proportion of subjects achieving endoscopic response, defined as a decrease from baseline of at least 1 point in the Mayo endoscopic subscore [ Time Frame: Up to approximately 8 weeks ] [ Designated as safety issue: No ]
    Mayo endoscopic subscore is one of Mayo score component and it ranges from 0 to 3 points

  • The proportion of subjects achieving clinical remission in the total Mayo score (TMS), defined as a TMS of ≤ 2, with no individual subscore > 1 [ Time Frame: Up to approximately 8 weeks ] [ Designated as safety issue: No ]
    The TMS is an instrument designed to measure disease activity of Ulcerative Colitis. The TMS ranges from 0 to 12 points. It consists of 4 subscores, each graded from 0 to 3 with higher scores indicating more severe disease

  • The proportion of subjects achieving clinical response in the total Mayo score (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 [ Time Frame: Up to approximately 8 weeks ] [ Designated as safety issue: No ]
    The TMS is an instrument designed to measure disease activity of Ulcerative Colitis. The TMS ranges from 0 to 12 points. It consists of 4 subscores, each graded from 0 to 3 with higher scores indicating more severe disease

  • Adverse Events (AEs) [ Time Frame: Up to approximately 52 weeks ] [ Designated as safety issue: Yes ]
    Assessed by the type, frequency and severity of adverse events, and its relationship to investigational product (IP), discontinuation due to adverse events, and clinically significant changes in vital signs, Electrocardiograms (ECGs), and/or laboratory findings


Estimated Enrollment: 40
Study Start Date: January 2016
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GED-0301 160 mg once daily (QD)
Patients will receive oral GED-0301 160 mg once daily (QD)for duration of 52 week treatment.
Drug: GED-0301
Other Name: Mongersen

Detailed Description:

Eligible subjects will have the Baseline Visit (Week 0/ Visit 2) and receive the following treatments:

  • Induction Phase - GED-0301 160 mg once daily (QD) for 8 weeks;
  • Extension Phase - GED-0301 160 mg on alternating dosing schedule (GED-0301 160 mg QD for 4 weeks, followed by 4 weeks without GED-0301 treatment) for an additional 44 weeks. Subjects who do not achieve at least a 20% decrease in partial mayo score (PMS) from baseline at Week 12 will be discontinued from the study.

Clinical, safety, and pharmacokinetic (PK) data will be evaluated on an ongoing basis, however, if the response to treatment is lower than expected (eg, ≤2 subjects achieving clinical remission based on modified Mayo score (MMS)) when 50% of the subjects complete Week 8, or discontinue before Week 8, the study team will review available data (clinical, safety, and PK) to evaluate if the study conduct should be modified.

This evaluation will be based on clinical judgment and the following guidance

  • Consider starting a new cohort of subjects using a QD dose up to 320 mg if there is endoscopic or histologic evidence of proximal colon benefit but limited or no distal colon drug exposure/efficacy. Also, there is evidence of potential overall efficacy (total Mayo score (TMS), MMS,PMS) outcomes and acceptable safety (adverse events (AEs)/vitals/clinical laboratory test results) and exposure (PK).
  • Consider to terminate the study if there is no evidence of drug exposure/efficacy in the colon observed by endoscopy or biopsy nor evidence of potential overall efficacy (TMS, MMS, PMS) outcomes or unacceptable safety(AEs/labs/vitals) or exposure (PK).
  • Continue the study with the GED-0301 160 mg QD dose. If the GED-0301 160 mg QD dose group is discontinued and a new dose group is added, an additional 40 subjects will be enrolled in the new dose group. Subjects enrolled subsequent to the decision to adjust the dose of GED-0301, will receive the following treatments:
  • Induction Phase - GED-0301, up to 320 mg QD, for 8 weeks;
  • Extension Phase- GED-0301, up to 320 mg on alternating dosing schedule (GED-0301, up to 320 mg QD for 4 weeks, followed by 4 weeks without GED-0301 treatment) for an additional 44 weeks. Subjects who do not achieve at least a 20% decrease in the PMS from baseline at Week 12 will be discontinued from the study. Actively enrolled subjects will not be affected by the dose adjustment. Subjects receiving corticosteroids at baseline will start tapering their corticosteroids at Week 8 (the end of the Induction Phase) if they achieve clinical response, 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 in the MMS. The endoscopy subscore assessed by the investigator will be used for the calculation of the Week 8 MMS.

The study will consist of 4 phases:

  • Screening Phase - up to 4 weeks
  • Induction Phase - 8 weeks
  • Extension Phase - 44 weeks
  • Observational Follow-up Phase - 4 weeks Subjects who complete the Extension Phase, and those subjects who prematurely discontinue from the study for any reason, will enter the post-treatment Observational Follow-up Phase, the 4-week period after the last dose of Investigational Product(IP). The study will be conducted in compliance with International Conference on Harmonisation (ICH) Good Clinical Practices (GCPs).
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02601300

Contacts
Contact: Associate Director Clinical Trial Disclosure 1-888-260-1599 clinicaltrialdisclosure@celgene.com

  Show 53 Study Locations
Sponsors and Collaborators
Celgene Corporation
Investigators
Study Director: Keith Usiskin, M.D Celgene Corporation
  More Information

Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT02601300     History of Changes
Other Study ID Numbers: GED-0301-UC-002 
Study First Received: November 6, 2015
Last Updated: May 11, 2016
Health Authority: United States: Food and Drug Administration
Bulgaria: Bulgarian Drug Agency
Hungary: National Institute of Pharmacy
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Slovakia: State Institute for Drug Control

Keywords provided by Celgene Corporation:
Ulcerative Colitis
GED-0301
Mongersen
Efficacy
Safety

Additional relevant MeSH terms:
Colitis
Ulcer
Colitis, Ulcerative
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases

ClinicalTrials.gov processed this record on July 21, 2016