A Long-term Active Treatment Study of Mongersen (GED-0301) in Subjects With Crohn's Disease

Study Overview
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Brief Summary
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The purpose of this study is to assess long-term safety data of GED-0301 for a period of up to 208 weeks in adult subjects (i.e., ≥ 18 years of age) who participated in the core Phase 3 GED-0301-CD-002 and GED-0301-CD-003 studies and adolescent subjects (i.e., 12 to 17 years of age) who participated in the core Phase 3 GED-0301-CD-003 study. Although all subjects will receive active treatment, this study is double-blinded for the entire 208 weeks for the purpose of preserving the blind of the subject's treatment allocation in the initial, core Phase 3 GED-0301 study. The GED-0301-CD-003 trial was not initiated; see detailed description.

Detailed Description
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This is a long-term active treatment study in patients with Crohn's disease (CD). Subjects who met the early escape criteria in Study GED-0301-CD-002, or subjects who completed Study GED-0301-002 or GED-0301-003, may be eligible for this study. Primary objective is to assess long-term safety of GED 0301. Additional efficacy and patient reported outcomes will be explored. There are 5 possible treatment groups for GED-0301-CD-002 Subjects (Groups 1-5). There are 3 possible treatment groups for GED-0301-CD-003 subjects (Groups 1-3). Treatment is assigned based on clinical improvement achieved or not achieved from the core GED-0301 study. continuous GED-0301 160 mg once daily for 12 weeks, followed by alternating placebo once daily for 4 weeks with GED-0301 160 mg once daily for 4 weeks, through Week 208; alternating GED-0301 160 mg once daily for 4 weeks with placebo once daily for 4 weeks, through Week 208; alternating placebo once daily for 4 weeks with GED-0301 160 mg once daily for 4 weeks, through Week 208; continuous GED-0301 40 mg once daily through Week 208; alternating placebo once daily for 4 weeks, followed by GED-0301 40 mg once daily for 4 weeks, through Week 208. The GED-0301-CD-003 trial was not initiated; the GED-0301 program was terminated; no safety findings were noted.

Official Title
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A Phase 3, Long-term Active Treatment Extension Study of Mongersen (GED-0301) in Subjects With Crohn's Disease

Conditions
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Crohn's Disease

Intervention / Treatment
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* Drug: GED-0301
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for Adult Subjects: Subjects must satisfy the following criteria to be screened and enrolled in the study: Male or female ≥ 18 years of age. Subject must have participated in the GED-0301-CD-002 or GED 0301 CD 003 study. Subject must use protocol approved contraception. Inclusion Criteria for Adolescent Subjects: Adolescent subjects must satisfy the following criteria to be screened and enrolled in the study Male or female 12 to 17 years of age. Subject must have participated in the GED 0301 CD 003 study. Subject is able to swallow the IP tablets. Subject must use protocol approved contraception. Exclusion Criteria for Adult and Adolescent Subjects: The presence of any of the following will exclude a subject from screening and enrollment: Subject had experienced a serious adverse event (SAE) related to the investigational product while participating in the previous Phase 3 GED-0301 study. Subject has initiated biologic agents, such as TNF-α blockers or integrin antagonists. Subject is pregnant or breastfeeding. Subject has developed a known hypersensitivity to oligonucleotides, GED 0301 or any ingredient in the investigational product.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GED-0301 (160 mg) followed by Placebo intermittent 160 mg<br>GED-0301 160 mg once daily (QD) for 12 weeks, followed by alternating Placebo (PBO) QD for 4 weeks with GED 0301 160 mg QD for 4 weeks, up to 208 weeks, if the subject previously received Placebo in the prior GED-0301 Study | Drug: GED-0301<br>* Mongersen<br>* Other names: Mongersen;|
| Experimental: Intermittent GED-0301 160 mg and placebo<br>Alternating GED-0301 160 mg once daily (QD) for 4 weeks with placebo (PBO) QD for 4 weeks, up to 208 weeks, depending on previous response in the prior GED-0301 study | Drug: GED-0301<br>* Mongersen<br>* Other names: Mongersen;Other: Placebo<br>* Placebo<br>|
| Experimental: Intermittent placebo and GED-0301 40 mg<br>Alternating PBO once daily (QD) for 4 weeks with GED-0301 40 mg QD for 4 weeks with, up to 208 weeks, depending on previous response in the prior GED-0301 study | Drug: GED-0301<br>* Mongersen<br>* Other names: Mongersen;Other: Placebo<br>* Placebo<br>|
| Experimental: Continuous GED-0301 40 mg<br>GED-0301 40 mg once daily (QD) for up to 208 weeks | Drug: GED-0301<br>* Mongersen<br>* Other names: Mongersen;|
| Experimental: Intermittent placebo and GED-0301 160 mg<br>Alternating PBO QD for 4 weeks with GED-0301 160 mg QD for 4 weeks, through Week 208 | Drug: GED-0301<br>* Mongersen<br>* Other names: Mongersen;Other: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Adverse Events From Week 0 to Week 208 | A TEAE was defined as any adverse event (AE) occurring or worsening on or after the first treatment of GED-0301 and up to 28 days after the last GED- 0301 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. | From the first day of GED-0301 until 28 days after the last dose of IP; maximum treatment duration was 16.1 weeks in the GED-0301 40 mg Alt dose; 16.3 weeks in the GED 40 mg continuous dose and 56.1 weeks in the GED-0301 160 mg Alt dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Crohn's Disease, GED 0301, Mongersen, Safety, Irritable Bowel Disease