Colitis, UlcerativePhase 2NCT02601300
An Efficacy and Safety Study of Mongersen (GED-0301) in Subjects With Active Ulcerative Colitis
A Phase 2 study testing GED-0301 in people with Colitis, Ulcerative, run by Celgene at 36 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colitis, Ulcerative
- What is being tested?
- GED-0301
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 36 sitesin 6 countries
- Study dates
- 14 Dec 2015to 8 Aug 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects must satisfy the following criteria to be enrolled in the study:
- Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF).
- Subject is able to understand and voluntarily sign an informed consent form (ICF)prior to conducting any study related assessments/procedures.
- Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
- Subject must have diagnosis of Ulcerative Colitis (UC) with a duration of at least 3 months prior to screening.
- 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.
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- Subject must have a Mayo endoscopic subscore ≥ 2 at screening.
- 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)
- Subject must meet the following laboratory criteria:
- White blood cell count ≥ 3000/mm3 (≥ 3.0 X 109/L)
- Platelet count ≥ 100,000/mm3 (≥ 100 X 109/L)
- Serum creatinine ≤ 1.5 mg/dL (≤ 132.6 μmol/L)
- Aspartate transaminase (AST/serum glutamic oxaloacetic transaminase (SGOT)) and alanine transaminase (ALT/serum pyruvic transaminase (SGPT)2.5 X upper limit of normal (ULN)
- Total bilirubin ≤ 2 mg/dL (≤ 34 μmol/L) unless there is a confirmed diagnosis of Gilbert's disease
- Hemoglobin ≥ 9 g/dL (≥ 5.6 mmol/L)
- Activated partial thromboplastin time (APTT) 1.5 X ULN
- 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.
- 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.
Who cannot join
- The presence of any of the following will exclude a subject from enrollment:
- Subject has a diagnosis of Crohn's Disease (CD), indeterminate colitis, ischemic colitis, microscopic colitis, radiation colitis or diverticular disease-associated colitis.
- Subject has ulcerative colitis restricted to distal 15 cm or less (eg, ulcerative proctitis).
- 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.
- Subject has clinical signs suggestive of fulminant colitis or toxic megacolon.
- Subject is stool positive for any enteric pathogen or Clostridium difficile (C. difficile) toxin at screening.
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- Subject has history of colorectal cancer or colorectal dysplasia.
- Prior treatment with more than 2 Tumor necrosis factor (TNF)-α blockers (eg, infliximab, adalimumab, or golimumab).
- Prior treatment with any integrin antagonists (eg, natalizumab or vedolizumab).
- Use of Tumor necrosis factor (TNF)-α blockers within 8 weeks of the screening.
- 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.
- Subject has received intravenous (IV) corticosteroids within 2 weeks of screening.
- Subject has received topical treatment with 5 aminosalicylic acid (5-ASA) or corticosteroid enemas or suppositories within 2 weeks of screening.
- Subject has received total parenteral nutrition (TPN) within 4 weeks of screening.
- 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.
- 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.
- Subject is pregnant or breastfeeding.
- 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.
- 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.
- Subject has a history of congenital or acquired immunodeficiency (eg, common variable immunodeficiency disease).
- Subject has a history of malignancy, except for:
- Treated (ie, cured) basal cell or squamous cell in situ skin carcinomas
- Treated (ie, cured) cervical intraepithelial neoplasia or carcinoma in situ of the cervix with no evidence of recurrence within the previous 5 years
- Subject has received investigational drug or device within 1 month of screening.
- Subject has a history of alcohol, drug, or chemical abuse within the 6 months prior to screening.
- Subject has a known hypersensitivity to oligonucleotides or any ingredient in the Investigational Product (IP).
- Subject has prior treatment with GED-0301 or participated in a clinical study involving GED-0301.
Trial locations and contacts
36 sites in 6 countries.
36 sites in 6 countries
United States20 sites
Chevy Chase Clinical Research
Chevy Chase, Maryland, 20815
Case Western Reserve University
Cleveland, Ohio, 44106
Texas Digestive Disease Consultants - Dallas
Dallas, Texas, 75231
Florida Research Network, LLC
Gainesville, Florida, 32605
Gastroenterology Center of The Midsouth PC
Germantown, Tennessee, 38138
Baylor College of Medicine
Houston, Texas, 77030
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, 03756
University of Kentucky
Lexington, Kentucky, 40536
Dean Medical Center
Madison, Wisconsin, 53715
University of Miami School of Medicine
Miami, Florida, 33136
Gastroenterology Group of Naples
Naples, Florida, 34102
Nashville Gastrointestinal Specialists
Nashville, Tennessee, 37211
Vanderbilt University
Nashville, Tennessee, 37212
Concorde Medical Group
New York, New York, 10016
Macks Research Group
Newport Beach, California, 92660
McGuire Veterans Affairs Medical Center
Richmond, Virginia, 23249
Rochester General Hospital
Rochester, New York, 14621
Medical Associates Research Associates
San Diego, California, 92123
Texas Digestive Disease Consultants - Southlake
Southlake, Texas, 76092
Shafran Gastroenterology Center
Winter Park, Florida, 32789
Slovakia5 sites
Fakultna nemocnica s poliklinikou F. D. Roosevelta
Banská Bystrica, 975 17
Univerzitna nemocnica Bratislava
Bratislava, 82606
IBD Centrum s.r.o.
Bratislava, 83104
KM Management, spol. s r.o.
Nitra, 949 01
GASTRO I., s.r.o.
Prešov, 080 01
Poland4 sites
Centrum Medyczne sw. Lukasza
Częstochowa, 42-200
Endoskopia Sp. z o.o.
Sopot, 81-756
Centrum Zdrowia Matki, Dziecka i Mlodziezy
Warsaw, 00-632
LexMedica Osrodek Badan Klinicznych
Wroclaw, 53-025
Bulgaria3 sites
Multiprofile Hospotal for Active Treatment- Sveti Nikolay Chudotvoretz - LOM EOOD
Lom, 3600
Multiprofile Hospital for Active Treatment Doverie AD
Sofia, 1632
Multiprofile Hospital for Active Treatment Sveti Panteleimon - Sofia AD
Sofia, 1712
Canada3 sites
London Health Sciences Centre, University Hospital
London, Ontario, N6A 5A5
GI Research Institute
Vancouver, British Columbia, V6Z 2K5
Toronto Digestive Disease Associates Inc
Vaughan, Ontario, L4L 4Y7
About this study
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.
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.
Read the 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).
- Conditions
- Colitis, Ulcerative
- Being tested
- GED-0301
- Keywords
- Ulcerative Colitis, GED-0301, Mongersen, Efficacy, Safety
- Medical subject headings
- Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GED-0301Drug
Also called Mongersen
| Study group | Role | What they receive |
|---|---|---|
| GED-0301 160 mg once daily (QD) | Experimental | Patients will receive oral GED-0301 160 mg once daily (QD)for duration of 52 week treatment. Receives: Drug: GED-0301 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants Who Achieved Clinical Remission in the Modified Mayo Score (MMS) at Week 8
Clinical remission was defined as a modified Mayo score of ≤ 2, with no individual subscore > 1, at Week 8. The MMS was based on a modification of the total Mayo score (TMS) which included the stool frequency, rectal bleeding, and endoscopic subscores of the TMS and excluded the Physician's Global Assessment (PGA) subscore, since this was a global measure that is subjective in nature. The MMS ranges from 0 to 9 points with higher scores indicating greater disease severity. The endoscopy subscores was centrally reviewed. Two-sided confidence intervals for the within-group percentage were based on the Wilson score method.
Measured: Baseline to Week 8
Secondary outcomes (8)
Percentage of Participants Who Achieved a Modified Mayo Score of ≤ 2, With Rectal Bleeding Subscore (RBS) of 0 and Stool Frequency Subscore (SFS) and Mayo Endoscopic Subscore ≤ 1 at Week 8
A MMS was used to evaluate disease activity using 3 components: stool frequency, rectal bleeding and endoscopy; the MMS ranges from 0-9 with higher scores indicating greater disease severity.
Stool frequency subscore was defined as 0-3:
0 = Normal number of stools for patient
- = 1-2 stools per day more than normal
- = 3-4 stools more than normal
- = 5 or more stools more than normal
Rectal bleeding (subscore 0-3) was defined as:
0 = No blood seen
- = Streaks of blood with stool less than half the time
- = Obvious blood with stool most of the time
- = Blood alone passes
Endoscopic subscore: Findings were defined as:
0 = Normal or inactive disease
- = Mild Disease (erythema, decreased vascular pattern, mild friability)
- = Moderate Disease (marked erythema, lack of vascular pattern, friability erosions)
- = Severe Disease (spontaneous bleeding, ulceration)
Measured: Baseline to Week 8
Percentage of Participants Who Achieved a Mayo Endoscopic Subscore of ≤ 1 at Week 8
A Mayo endoscopic subscore of ≤ 1 was assessed and evaluated in participants who achieved a Mayo endoscopic subscore at Week 8. The endoscopy subscore findings are defined as:
0 = Normal or inactive disease
- = Mild Disease (erythema, decreased vascular pattern, mild friability)
- = Moderate Disease (marked erythema, lack of vascular pattern, friability erosions)
- = Severe Disease (spontaneous bleeding, ulceration) The endoscopy scores were centrally reviewed. Two-sided 95% CIs for the within-group percentage were based on the Wilson score method.
Measured: Baseline to Week 8
Percentage of Participants Who Achieved a Mayo Endoscopic Subscore of ≤ 1 by Individual Segment at Week 8
A Mayo endoscopic subscore by individual segment (rectum, sigmoid, descending colon, transverse colon, ascending colon/cecum) of ≤ 1 was evaluated at week 8.
The endoscopy subscore findings are defined as:
0 = Normal or inactive disease
- = Mild Disease (erythema, decreased vascular pattern, mild friability)
- = Moderate Disease (marked erythema, lack of vascular pattern, friability erosions)
- = Severe Disease (spontaneous bleeding, ulceration) The endoscopy scores were centrally reviewed. Two-sided 95% CIs for the within-group percentage were based on the Wilson score method.
Measured: Baseline to Week 8
Percentage of Participants Who Achieved a Clinical Response in the Modified Mayo Score at Week 8
Clinical response in the MMS was 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 ≤ 1. The MMS was based on the stool frequency, rectal bleeding, and endoscopic subscores of the TMS and excluded the PGA subscore. The MMS ranges from 0 to 9 points with higher scores indicating greater disease severity. The RBS was defined as:
0 = No blood seen
- = Streaks of blood with stool less than half the time
- = Obvious blood with stool most of the time
- = Blood alone passes The daily bleeding score represents the most severe bleeding score represents the most severe bleeding of the day.
Measured: Baseline to Week 8
Percentage of Participants Who Achieved a Mayo Endoscopic Response at Week 8
Endoscopic response was defined as a decrease from baseline of at least 1 point in the Mayo endoscopic subscore. The Mayo endoscopy subscore findings are defined as:
0 = Normal or inactive disease
- = Mild Disease (erythema, decreased vascular pattern, mild friability)
- = Moderate Disease (marked erythema, lack of vascular pattern, friability erosions)
- = Severe Disease (spontaneous bleeding, ulceration) The endoscopy subscores were centrally reviewed. Two-sided 95% CIs for the within-group percentage were based on the Wilson score method.
Measured: Baseline and Week 8
Percentage of Participants Who Achieved a Clinical Remission in the Total Mayo Score (TMS) at Week 8
Clinical remission in total Mayo score was defined as a total Mayo score of ≤ 2, with no individual subscore >1. 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.
- Stool frequency subscore (SFS)
- Rectal bleeding subscore (RBS)
- Endoscopic subscore
- Physician's Global Assessment (PGA)
Measured: Baseline to Week 8
Percentage of Participants Who Achieved a Clinical Response in the Total Mayo Score at Week 8
Clinical response in the TMS was defined as a decrease from baseline in the TMS of ≥ 3 points and ≥ 30%, along with a reduction in the RBS of ≥ 1 point or an absolute RBS of ≤ 1 at Week 8. 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.
- Stool frequency subscore
- Rectal bleeding subscore
- Endoscopic subscore
- Physician's Global Assessment
Measured: Baseline to Week 8
The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE)
A TEAE was defined as any adverse event (AE) occurring or worsening on or after the first treatment of mongersen and up to 28 days after the last mongersen dose or the last follow-up date, whichever occurred earlier. A serious AE = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was assessed by the investigator and based on the following scale: Mild = asymptomatic or mild symptoms; clinical or diagnostic observations only; Moderate = Symptoms cause moderate discomfort; Severe (could be non-serious or serious) = symptoms causing severe discomfort/pain.
Measured: From the first day of mongersen until 28 days after the last dose of IP or at follow-up visit, whichever occurred earlier; maximum duration of treatment was 56 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2015 (estimated)
- Study start14 Dec 2015
- Primary completion6 Sep 2016
- Study completion8 Aug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Colitis, UlcerativeStudies of the same condition, open and under way.
- More trials run by CelgeneThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- Celgene
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Keith Usiskin, M.D, Study director, Celgene Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02601300
- Sponsor's protocol ID
- GED-0301-UC-002
- Status last verified
- Oct 2018
- First submitted
- 6 Nov 2015
- Last updated
- 17 Oct 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT02601300
- Acronym / sponsor ID
- GED-0301-UC-002
- Conditions
- Colitis, Ulcerative
- Keywords
- Ulcerative Colitis, GED-0301, Mongersen, Efficacy, Safety
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- CelgeneIndustry (pharma, biotech, devices)
- Study start
- 14 Dec 2015 (actual)
- Primary completion
- 6 Sep 2016 (actual)
- Study completion
- 8 Aug 2017 (actual)
- First posted
- 10 Nov 2015 (estimated)
- Results
- Posted 12 Sep 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| GED-0301 160 mg once daily (QD) | Experimental | Drug: GED-0301Patients will receive oral GED-0301 160 mg once daily (QD)for duration of 52 week treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Subjects must satisfy the following criteria to be enrolled in the study:
- 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)
Key exclusion criteria (27 listed)
- The presence of any of the following will exclude a subject from enrollment:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GED-0301Also: Mongersen | Drug | GED-0301 160 mg once daily (QD) |
Primary outcome
Percentage of Participants Who Achieved Clinical Remission in the Modified Mayo Score (MMS) at Week 8
Time frame: Baseline to Week 8
Clinical remission was defined as a modified Mayo score of ≤ 2, with no individual subscore > 1, at Week 8. The MMS was based on a modification of the total Mayo score (TMS) which included the stool frequency, rectal bleeding, and endoscopic subscores of the TMS and excluded the Physician's Global Assessment (PGA) subscore, since this was a global measure that is subjective in nature. The MMS ranges from 0 to 9 points with higher scores indicating greater disease severity. The endoscopy subscores was centrally reviewed. Two-sided confidence intervals for the within-group percentage were based on the Wilson score method.
8 secondary outcomes
Percentage of Participants Who Achieved a Modified Mayo Score of ≤ 2, With Rectal Bleeding Subscore (RBS) of 0 and Stool Frequency Subscore (SFS) and Mayo Endoscopic Subscore ≤ 1 at Week 8
Time frame: Baseline to Week 8
Percentage of Participants Who Achieved a Mayo Endoscopic Subscore of ≤ 1 at Week 8
Time frame: Baseline to Week 8
Percentage of Participants Who Achieved a Mayo Endoscopic Subscore of ≤ 1 by Individual Segment at Week 8
Time frame: Baseline to Week 8
Percentage of Participants Who Achieved a Clinical Response in the Modified Mayo Score at Week 8
Time frame: Baseline to Week 8
Percentage of Participants Who Achieved a Mayo Endoscopic Response at Week 8
Time frame: Baseline and Week 8
Percentage of Participants Who Achieved a Clinical Remission in the Total Mayo Score (TMS) at Week 8
Time frame: Baseline to Week 8
Percentage of Participants Who Achieved a Clinical Response in the Total Mayo Score at Week 8
Time frame: Baseline to Week 8
The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE)
Time frame: From the first day of mongersen until 28 days after the last dose of IP or at follow-up visit, whichever occurred earlier; maximum duration of treatment was 56 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Oct 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Keith Usiskin, M.D study director
Celgene Corporation
36 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GED-0301 in people with Colitis, Ulcerative, run by Celgene at 36 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 36 sites in United States, Slovakia, Poland, Bulgaria, Canada and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Sep 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants Who Achieved Clinical Remission in the Modified Mayo Score (MMS) at Week 8 (time frame: Baseline to Week 8). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Oct 2018.