Efficacy and Safety Study of Mongersen (GED-0301) for the Treatment of Subjects With Active Crohn's Disease

Study Overview
=================
Brief Summary
-----------------
The purpose of study is to test the effects of an experimental medication GED-0301 (mongersen) in patients who have active Crohn's disease. The study will test GED-0301 compared to placebo for 52 weeks. The study treatment is blinded which means that patients and the study doctor will not know which treatment has been assigned. Patients in this study will be allowed treatment with stable doses of oral aminosalicylates, oral corticosteroids, immunosupressants and antibiotics for the treatment of Crohn's disease. After 12 weeks in the study until the end of the study, patients who do not have an improvement in their Crohns disease symptoms will have the option to enter a long term active treatment study. Participants who discontinued the study anytime or completed the study at Week 52 were then observed for an additional 4 weeks.

Official Title
-----------------
A Phase 3, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Investigate the Efficacy and Safety of Mongersen (GED-0301) for the Treatment of Subjects With Active Crohn's Disease

Conditions
-----------------
Crohn Disease

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects must satisfy the following criteria to be enrolled in the study: Male or female ≥ 18 years Active Crohn's disease (CD) disease as determined by the Crohn's Disease Activity Index (CDAI) score and the Simple Endoscopic Score for Crohn's Disease (SES-CD) Must meet a determined average minimum number of daily stools or rating of abdominal pain over a 7 day period Subject must have failed or experienced intolerance to at least one of the following: budesonide; systemic corticosteroids; immunosuppressants (eg, azathiopurine, 6-mercaptopurine, or methotrexate); or biologics for the treatment of CD. Exclusion Criteria: The presence of any of the following will exclude a subject from enrollment: Diagnosis of ulcerative colitis (UC), indeterminate colitis, ischemic colitis, microscopic colitis, radiation colitis or diverticular disease-associated colitis Local manifestations of Crohn's Disease (CD) such as symptomatic/severe strictures, abscesses, short bowel syndrome; or other disease complications for which surgery might be indicated or could confound the evaluation of efficacy Intestinal resection within 6 months or any intra-abdominal surgery within 3 months prior to the Screening Visit Ileostomy or a colostomy Subject has a history of any clinically significant medical condition that, in the investigator's opinion, would prevent the subject from participating in the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GED0301 160mg x 12 weeks followed by periodic 160 mg GED0301<br>GED-0301 160 mg once daily (QD) for 12 weeks; followed by placebo QD for 4 weeks; followed by alternating GED-0301 160 mg QD for 4 weeks and placebo QD for 4 weeks, until the the Week 52 Visit | Drug: GED-0301<br> <br> Drug: Placebo<br> <br> |
| Experimental: GED0301 160mg x 12 weeks followed by periodic GED0301 40mg<br>GED-0301 160 mg once daily (QD) for 12 weeks; followed by placebo QD for 4 weeks; followed by alternating GED-0301 40 mg QD for 4 weeks and placebo QD for 4 weeks, until the Week 52 Visit | Drug: GED-0301<br> <br> Drug: Placebo<br> <br> |
| Experimental: GED0301 160mg x 12 weeks followed by continuous GED0301 40mg<br>GED-0301 160 mg once daily (QD) for 12 weeks; followed by continuous GED-0301 40 mg QD, until the Week 52 Visit | Drug: GED-0301<br> <br> |
| Placebo Comparator: Placebo<br>Placebo once daily (QD) until the Week 52 Visit | Drug: Placebo<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Participants Who Achieved a Clinical Remission at Week 12 | Clinical remission is defined as a Crohn's Disease Activity Index (CDAI) score < 150. The Crohn's Disease Activity Index is used to quantify the signs and symptoms of Crohn's disease and the affect on patient's quality of life. It consists of 8 variables which include patient reported outcomes over a 7 day period and physician assessments which are scored numerically and weighted. Scores range from 0 to 600, with the most severe disease defined >450. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved Clinical Remission at Week 52 | Clinical remission is defined as a CDAI score < 150 and is used to quantify the signs and symptoms of Crohn's disease and the effect on patient's quality of life. It consists of 8 variables which include patient reported outcomes over a 7 day period and physician assessments which are scored numerically and weighted. Scores range from 0 to 600, with the most severe disease defined >450. | Week 52 | 
| Percentage of Participants With Endoscopic Response-50 Centrally Read at Week 52 | An endoscopic response-50 is defined as a reduction of at least 50% compared with baseline in simple endoscopic score for Crohn's Disease (SES-CD). The SES-CD assesses the size of mucosal ulcers, the extent of ulcerated surface, the extent of affected surface, and the presence and type of narrowings. Scores range from 0 to 60 with higher scores reflecting more severe disease. The SES-CD calculations include: Ulcers scored as: 0: no aphthous (0.1-0.5 cm) large (0.5-2 cm) very large (>2 cm) Surface involved disease 0: 0% <50% 50-75% >75% Surface involved by ulcerations: 0: 0% <10% 10-30% >30% - Narrowings: 0: No Single, can be passed Multiple, can be passed Cannot be passed Grand Total = SES-CD score | Week 52 | 
| The Percentage of Participants Who Achieved a Clinical Response at Week 12 | A clinical response is defined as a CDAI score decrease from baseline ≥ 100 points. The CDAI is used to quantify the signs and symptoms of Crohn's disease and the effect on patient's quality of life. It consists of 8 variables which include patient reported outcomes over a 7 day period and physician assessments which are scored numerically and weighted. Scores range from 0 to 600, with the most severe disease defined >450. | Week 12 | 
| The Percentage of Participants Who Achieved a Clinical Response at Week 4 | A clinical response is defined as a decrease from baseline in CDAI ≥ 100 points. The Crohn's Disease Activity Index is used to quantify the signs and symptoms of Crohn's disease and the effect on patient's quality of life. It consists of 8 variables which include patient reported outcomes over a 7 day period and physician assessments which are scored numerically and weighted. Scores range from 0 to 600, with the most severe disease defined >450. | Week 4 | 
| The Percentage of Participants Who Achieved a Clinical Remission at Week 4 | A clinical remission is a CDAI score < 150. The Crohn's Disease Activity Index is used to quantify the signs and symptoms of Crohn's disease and the effect on patient's quality of life. It consists of 8 variables which include patient reported outcomes over a 7 day period and physician assessments which are scored numerically and weighted. Scores range from 0 to 600, with the most severe disease defined >450. | Week 4 | 
| The Percentage of Participants Who Achieved a Corticosteroid-Free Clinical Remission at Week 52 | The percentage of participants who were receiving oral corticosteroids for Crohn's disease, at baseline and achieved a clinical remission (CDAI score <150) at Week 52 without corticosteroids. The Crohn's Disease Activity Index is used to quantify the signs and symptoms of Crohn's disease and the effect on patient's quality of life. It consists of 8 variables which include patient reported outcomes over a 7 day period and physician assessments which are scored numerically and weighted. Scores range from 0 to 600, with the most severe disease defined >450. | Week 52 | 
| Percentage of Participants Who Achieved a Sustained Clinical Remission at Both Week 12 and 52 | For participants who achieved a sustained clinical remission at both week 12 and 52, the clinical remission is a CDAI score < 150. The Crohn's Disease Activity Index is used to quantify the signs and symptoms of Crohn's disease and the effect on patient's quality of life. It consists of 8 variables which include patient reported outcomes over a 7 day period and physician assessments which are scored numerically and weighted. Scores range from 0 to 600, with the most severe disease defined >450. | Weeks 12 and 52 | 
| Percentage of Participants With Endoscopic Response-25 Centrally Read at Week 12 | An endoscopic response-25 is defined as a reduction of at least 25% compared with baseline in simple endoscopic score for Crohn's disease (SES-CD). The SES-CD assesses the size of mucosal ulcers, the extent of ulcerated surface, the extent of affected surface, and the presence and type of narrowings. Scores range from 0 to 60 with higher scores reflecting more severe disease. The SES-CD calculations include: Ulcers scored as: 0: no aphthous (0.1-0.5 cm) large (0.5-2 cm) very large (>2 cm) Surface involved disease 0: 0% <50% 50-75% >75% Surface involved by ulcerations: 0: 0% <10% 10-30% >30% - Narrowings: 0: No Single, can be passed Multiple, can be passed Cannot be passed Grand Total = SES-CD score | Week 0, Week 12 | 
| Percentage of Participants With Endoscopic Remission Centrally Read at Week 52 | Endoscopic remission is defined as a simple endoscopic score for Crohn's disease (SES-CD) of ≤2 at the specified timeframe. The SES-CD assesses the size of mucosal ulcers, the extent of ulcerated surface, the extent of affected surface, and the presence and type of narrowings. Scores range from 0 to 60 with higher scores reflecting more severe disease. The SES-CD calculations include: Ulcers scored as: 0: no aphthous (0.1-0.5 cm) large (0.5-2 cm) very large (>2 cm) Surface involved disease 0: 0% <50% 50-75% >75% Surface involved by ulcerations: 0: 0% <10% 10-30% >30% - Narrowings: 0: No Single, can be passed Multiple, can be passed Cannot be passed Grand Total = SES-CD score | Week 52 | 
| The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE) From Week 0 to Week 52 | 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. | From the first day of GED-0301 until 28 days after the last dose of investigational product (IP); maximum treatment duration was 52.6 weeks | 
| The Number of Participants Who Discontinued IP Due to an Treatment Emergent Adverse Events | A TEAE was defined as any AE occurring or worsening on or after the first dose 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 52.6 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
IBD, GED-0301, Safety, Efficacy, Crohn's Disease, Mongersen