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

Phase 3TerminatedNCT02596893

Celgene701 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

701

Conditions

Crohn Disease

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (538)

ADDC Research LLC

Huntsville, Alabama, United States

Arizona Digestive Health

Mesa, Arizona, United States

Mayo Clinic Arizona

Phoenix, Arizona, United States

Colon & Digestive Health Specialists

Scottsdale, Arizona, United States

Arizona Digestive Health

Sun City, Arizona, United States

Outcomes

Primary Outcomes

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.

Time frame: Week 12

Secondary Outcomes

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.

Time frame: 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 1. aphthous (0.1-0.5 cm) 2. large (0.5-2 cm) 3. very large (\>2 cm) * Surface involved disease 0: 0% 1. \<50% 2. 50-75% 3. \>75% Surface involved by ulcerations: 0: 0% 1. \<10% 2. 10-30% 3. \>30% - Narrowings: 0: No 1. Single, can be passed 2. Multiple, can be passed 3. Cannot be passed Grand Total = SES-CD score

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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 1. aphthous (0.1-0.5 cm) 2. large (0.5-2 cm) 3. very large (\>2 cm) * Surface involved disease 0: 0% 1. \<50% 2. 50-75% 3. \>75% Surface involved by ulcerations: 0: 0% 1. \<10% 2. 10-30% 3. \>30% - Narrowings: 0: No 1. Single, can be passed 2. Multiple, can be passed 3. Cannot be passed Grand Total = SES-CD score

Time frame: 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 1. aphthous (0.1-0.5 cm) 2. large (0.5-2 cm) 3. very large (\>2 cm) * Surface involved disease 0: 0% 1. \<50% 2. 50-75% 3. \>75% Surface involved by ulcerations: 0: 0% 1. \<10% 2. 10-30% 3. \>30% - Narrowings: 0: No 1. Single, can be passed 2. Multiple, can be passed 3. Cannot be passed Grand Total = SES-CD score

Time frame: 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.

Time frame: 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.

Time frame: From the first day of GED-0301 until 28 days after the last dose of IP; maximum treatment duration was 52.6 weeks