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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02367183




Registration number
NCT02367183
Ethics application status
Date submitted
13/02/2015
Date registered
20/02/2015
Date last updated
10/01/2019

Titles & IDs
Public title
A Randomized, Double-blind, Study to Explore the Effect of GED-0301 in Subjects With Active Crohn's Disease
Scientific title
A Randomized, Double-blind, Multicenter Study to Explore the Effect of GED-0301 on Endoscopic and Clinical Outcomes in Subjects With Active Crohn's Disease.
Secondary ID [1] 0 0
GED-0301-CD-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Crohn Disease 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Inflammatory bowel disease
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Oral and Gastrointestinal 0 0 0 0
Crohn's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental: GED-0301 160mg QD 12 WK - GED-0301 160 mg once daily (QD) for 12 weeks

Experimental: GED-0301 160 mg QD 8 WK - GED-0301 160 mg QD for 8 weeks followed by 4 weeks of placebo

Experimental: GED-0301 160 mg QD 4 WK - GED-0301 160 mg QD for 4 weeks followed by 8 weeks of placebo
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change in SES-CD Score
Timepoint [1] 0 0
Week 12
Secondary outcome [1] 0 0
Proportion of subjects achieving a clinical remission, defined as a CDAI score < 150 at Induction Week 4
Timepoint [1] 0 0
Week 4
Secondary outcome [2] 0 0
Adverse Event (AE)
Timepoint [2] 0 0
Up to 97 weeks

Eligibility
Key inclusion criteria
1. Is a male or female who is =18 years at the time of signing the Informed Consent Form (ICF).
2. Understand and voluntarily sign an Informed Consent Form (ICF) prior to conducting any study related assessments/procedures.
3. Able to adhere to the study visit schedule and other protocol requirements.
4. Diagnosis of Crohn's Disease (CD) with a duration of at least 3 months prior to screening.
5. Diagnosis of ileitis, ileocolitis or colitis , as determined by endoscopic, radiographic or any other imaging modality (eg, magnetic resonance imaging [MRI], computed tomography [CT] scan) evaluation performed within 2 years prior to screening. Subjects with colitis restricted to the left colon will not be allowed in the trial.
6. Active disease, defined as Crohn's Disease Activity Index (CDAI) score = 220 and = 450 (range: 0 to 600) at screening.
7. Simple Endoscopic Score for Crohn's Disease (SES-CD) score = 7 at screening. Subjects with ileitis only will require Simple Endoscopic Score for Crohn's Disease (SES-CD) = 4
8. Must have failed or experienced intolerance to at least one of the following:

aminosalicylates, budesonide, systemic corticosteroids, immunosuppressants (ie, 6 mercaptopurine [6-MP], azathioprine [AZA], or methotraxate [MTX]) or tumor necrosis factor-a tumor necrosis factor-a (TNF-a) blockers (eg, infliximab, adalimumab or certolizumab) .
9. Subjects receiving oral aminosalicylates may continue their use during the study, provided that dose has been stable for at least 2 weeks prior to screening. The dose of oral aminosalicylates must remain stable through the duration of the study or early termination from the study. If oral aminosalicylates have been recently discontinued, treatment must have been stopped at least 2 weeks prior to screening.
10. Subjects receiving oral corticosteroids may continue their use during the Induction Phase, provided that the dose (prednisone = 20 mg/day or equivalent, budesonide = 9 mg/day) has been stable for 3 weeks prior to screening. If oral corticosteroids were recently discontinued, discontinuation must have been completed at least 4 weeks prior to screening. Corticosteroid doses should remain stable until the subject is eligible to start corticosteroids tapering.
11. Subjects receiving immunosuppressants, such as , 6 mercaptopurine (6-MP), azathioprine (AZA), or methotraxate (MTX) may continue their use during the study, provided that treatment was initiated = 12 weeks prior to screening. The dose of immunosuppressants must be at a stable dose for = 8 weeks prior to the Baseline Visit and must remain stable through the duration of the study or early termination from the study. Subjects who discontinued immunosuppressants should have stopped them at least 8 weeks prior to screening.
12. Must meet the following laboratory criteria:

1. White blood cell count = 3000/mm3 (= 3.0 X 10^9//L) and < 14,000/mm3 (< 14.0 X 10^9/L)
2. Platelet count = 100,000/mm3 (= 100 X 10^9/L)
3. Serum creatinine = 1.5 mg/dL (= 132.6 µmol/L)
4. Aspartate aminotransferase (AST) / serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT) / serum glutamic-pyruvic transaminase (SGPT) = 2 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
13. Females of childbearing potential (FCBP) must have a negative pregnancy test at Screening and the Baseline Visit. While on IP and for at least 28 days after the Early Termination Visit or the end-of-study visit (Observation Week 52 or Extension Week 24), FCBP who engage in activity in which conception is possible must use 1 of the approved contraceptive options2 described below: Option 1: Any one of the following highly effective methods: hormonal contraception (for example, birth control pills, injection, implant, transdermal patch, vaginal ring); intrauterine device (IUD); tubal ligation (tying your tubes); or a partner with a vasectomy OR

Option 2: Any two of the following effective methods: male or female condom PLUS one of the following additional barrier methods:
1. diaphragm with spermicide;
2. cervical cap with spermicide; or
3. contraceptive sponge with spermicide
14. Male subjects (including those who have had a vasectomy) who engage in activity in which conception is possible 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 Early Termination Visit or the end-of-study visit (Observation Week 52 or Extension Week 24).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Diagnosis of Crohn's colitis restricted to the left colon , ulcerative colitis (UC), indeterminate colitis, ischemic colitis, microscopic colitis, radiation colitis or diverticular disease-associated colitis.
2. Local manifestations of Crohn's Disease (CD) such as strictures, abscesses, fistula, short bowel syndrome or other disease complications for which surgery might be indicated or could confound the evaluation of efficacy.
3. Intestinal resection within 6 months or any intra-abdominal surgery within 3 months prior to screening.
4. Subjects with an ileostomy or a colostomy.
5. Stool positive for any enteric pathogen or C. difficile toxin at screening.
6. History of colorectal cancer or colorectal dysplasia.
7. Prior use of mycophenolic acid, tacrolimus, sirolimus, cyclosporine, thalidomide or apheresis (eg, Adacolumn) for the treatment of CD. In addition, prior use of any of these treatment modalities for an indication other than CD within 8 weeks of screening is also excluded.
8. Use of intravenous (IV) corticosteroids within 2 weeks of screening.
9. Use of topical treatment with 5 aminosalicylic acid (5-ASA) or corticosteroid enemas or suppositories within 2 weeks of screening
10. Use of antibiotic therapy for the treatment of Crohn's Disease (CD) within 3 weeks of screening.
11. Use of cholestyramine within 3 weeks of screening.
12. Prior treatment with more than 2 tumor necrosis factor-a (TNF-a) blockers.
13. Prior treatment with any integrin antagonists (eg, natalizumab or vedolizumab).
14. Use of tumor necrosis factor-a (TNF-a) blockers within 12 weeks of the screening
15. Administration of total parenteral nutrition (TPN) within 4 weeks of screening.
16. 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.
17. 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.
18. Pregnant or breastfeeding.
19. 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.
20. Known active current or history of 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.
21. History of congenital or acquired immunodeficiency (eg, common variable immunodeficiency disease).
22. 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
23. Subjects who have received any investigational drug or device within 1 months of screening.
24. Prior treatment with GED-0301, or participation in a clinical study involving GED-0301.
25. History of alcohol, drug, or chemical abuse within the 6 months prior to screening.
26. Known hypersensitivity to oligonucleotides or any ingredient in the IP.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
8/04/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
14/12/2017
Sample size
Target
Accrual to date
Final
64
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Centre For Digestive Diseases - Five Dock
Recruitment hospital [2] 0 0
Mater Adult Hospital - South Brisbane
Recruitment hospital [3] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [4] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [5] 0 0
Concord Repatriation General Hospital - Concord
Recruitment postcode(s) [1] 0 0
2046 - Five Dock
Recruitment postcode(s) [2] 0 0
4101 - South Brisbane
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment postcode(s) [4] 0 0
3168 - Clayton
Recruitment postcode(s) [5] 0 0
2139 - Concord
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Kentucky
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
North Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Tennessee
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
United States of America
State/province [12] 0 0
Utah
Country [13] 0 0
United States of America
State/province [13] 0 0
Virginia
Country [14] 0 0
United States of America
State/province [14] 0 0
Washington
Country [15] 0 0
Canada
State/province [15] 0 0
British Columbia
Country [16] 0 0
Canada
State/province [16] 0 0
Ontario
Country [17] 0 0
Hungary
State/province [17] 0 0
Budapest
Country [18] 0 0
Hungary
State/province [18] 0 0
Szeged
Country [19] 0 0
Slovakia
State/province [19] 0 0
Banska Bystrica
Country [20] 0 0
Slovakia
State/province [20] 0 0
Bratislava
Country [21] 0 0
Slovakia
State/province [21] 0 0
Nitra
Country [22] 0 0
Slovakia
State/province [22] 0 0
Presov

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Celgene
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study is design to explore the effect of GED-0301 on clinical and endoscopic outcome and to evaluate its safety in subjects with active Crohn's disease.
Trial website
https://clinicaltrials.gov/study/NCT02367183
Trial related presentations / publications
Feagan BG, Sands BE, Rossiter G, Li X, Usiskin K, Zhan X, Colombel JF. Effects of Mongersen (GED-0301) on Endoscopic and Clinical Outcomes in Patients With Active Crohn's Disease. Gastroenterology. 2018 Jan;154(1):61-64.e6. doi: 10.1053/j.gastro.2017.08.035. Epub 2017 Aug 25.
Public notes

Contacts
Principal investigator
Name 0 0
Guillermo Rossiter, MD
Address 0 0
Celgene
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02367183