Crohn Disease
Conditions
Keywords
Crohn's Disease, GED-0301, Mongersen, IBD, Safety, Efficacy
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.
Interventions
DRUGGED-0301
DRUGPlacebo
Sponsors
Celgene
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Participants Who Achieved a Clinical Remission at Week 12 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Endoscopic Response-50 Centrally Read at Week 52 | 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 |
| The Percentage of Participants Who Achieved a Clinical Response at Week 12 | 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. |
| The Percentage of Participants Who Achieved a Clinical Response at Week 4 | 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. |
| The Percentage of Participants Who Achieved a Clinical Remission at Week 4 | 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. |
| The Percentage of Participants Who Achieved a Corticosteroid-Free Clinical Remission at Week 52 | 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. |
| Percentage of Participants Who Achieved Clinical Remission at Week 52 | 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. |
| Percentage of Participants With Endoscopic Response-25 Centrally Read at Week 12 | Week 0, 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 |
| Percentage of Participants With Endoscopic Remission Centrally Read at Week 52 | 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 |
| The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE) From Week 0 to Week 52 | 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 | 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 Number of Participants Who Discontinued IP Due to an Treatment Emergent Adverse Events | From the first day of GED-0301 until 28 days after the last dose of IP; maximum treatment duration was 52.6 weeks | 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. |
| Percentage of Participants Who Achieved a Sustained Clinical Remission at Both Week 12 and 52 | Weeks 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. |
Countries
Australia, Austria, Belgium, Bulgaria, Canada, Croatia, Czechia, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Israel, Italy, Latvia, Malaysia, Netherlands, New Zealand, Norway, Poland, Portugal, Romania, Russia, Serbia, Slovakia, South Korea, Spain, Sweden, Switzerland, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled at study centers within the United States and Canada, Australia, Eastern and Western Europe, Korea and Russia.
Pre-assignment details
Treatment assignment at baseline (Week 0) was stratified based on concomitant use of corticosteroids (yes/no), concomitant use of immunosuppressants (yes/no) or and previous exposure to biologics (yes/no),
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo daily up to week 52. | 174 |
| GED-0301 160 mg / GED-0301 40 mg 4 Week Alt Participants received GED-0301 160 mg daily for 12 weeks, followed by alternating placebo daily for 4 weeks and GED-0301 40 mg daily for 4 weeks, up to week 52. | 176 |
| GED-0301 160 mg / GED-0301 40 mg Participants received GED-0301 160 mg daily for 12 weeks, followed by continuous GED-0301 40 mg daily, up to week 52. | 176 |
| GED-0301 160 mg / GED-0301 160 mg 4 Week Alt Participants received GED-0301 160 mg daily for 12 weeks, followed by alternating placebo daily for 4 weeks and GED-0301 160 mg daily for 4 weeks, up to week 52. | 175 |
| Total | 701 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Double-Blind Period Weeks 0-52 | Adverse Event | 11 | 15 | 15 | 12 |
| Overall Double-Blind Period Weeks 0-52 | Death | 0 | 0 | 1 | 0 |
| Overall Double-Blind Period Weeks 0-52 | Early Escape | 66 | 76 | 69 | 70 |
| Overall Double-Blind Period Weeks 0-52 | Lack of Efficacy | 15 | 14 | 14 | 13 |
| Overall Double-Blind Period Weeks 0-52 | Lost to Follow-up | 0 | 1 | 1 | 1 |
| Overall Double-Blind Period Weeks 0-52 | Miscellaneous | 1 | 2 | 0 | 2 |
| Overall Double-Blind Period Weeks 0-52 | Non-Compliance with Study Drug | 0 | 0 | 1 | 2 |
| Overall Double-Blind Period Weeks 0-52 | Pregnancy | 0 | 0 | 0 | 1 |
| Overall Double-Blind Period Weeks 0-52 | Protocol Violation | 0 | 0 | 0 | 2 |
| Overall Double-Blind Period Weeks 0-52 | Study Terminated by Sponsor | 61 | 56 | 48 | 58 |
| Overall Double-Blind Period Weeks 0-52 | Withdrawal by Subject | 10 | 4 | 13 | 5 |
Baseline characteristics
| Characteristic | Total | GED-0301 160 mg / GED-0301 160 mg 4 Week Alt | GED-0301 160 mg / GED-0301 40 mg | GED-0301 160 mg / GED-0301 40 mg 4 Week Alt | Placebo |
|---|---|---|---|---|---|
| Age, Continuous | 38.5 Years STANDARD_DEVIATION 12.77 | 38.2 Years STANDARD_DEVIATION 12.47 | 39.6 Years STANDARD_DEVIATION 12.9 | 37.6 Years STANDARD_DEVIATION 12.84 | 38.5 Years STANDARD_DEVIATION 12.88 |
| Baseline Crohn's Disease Activity (CDAI) Score | 304.7 Units on a Scale STANDARD_DEVIATION 66.61 | 309.9 Units on a Scale STANDARD_DEVIATION 66.32 | 308.3 Units on a Scale STANDARD_DEVIATION 65.5 | 292.8 Units on a Scale STANDARD_DEVIATION 69.33 | 307.9 Units on a Scale STANDARD_DEVIATION 64.31 |
| Baseline Endoscopic Score for Crohn's Disease (Central Read) | 14.2 Units on a Scale STANDARD_DEVIATION 8.06 | 14.5 Units on a Scale STANDARD_DEVIATION 8.3 | 13.8 Units on a Scale STANDARD_DEVIATION 7.69 | 14.3 Units on a Scale STANDARD_DEVIATION 8.41 | 14.4 Units on a Scale STANDARD_DEVIATION 7.88 |
| Duration of Crohn's Disease | 9.54 Years STANDARD_DEVIATION 8.786 | 10.15 Years STANDARD_DEVIATION 9.353 | 9.84 Years STANDARD_DEVIATION 8.746 | 8.63 Years STANDARD_DEVIATION 7.877 | 9.57 Years STANDARD_DEVIATION 9.106 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 29 Participants | 8 Participants | 8 Participants | 2 Participants | 11 Participants |
| Race/Ethnicity, Customized Black or African American | 12 Participants | 2 Participants | 2 Participants | 4 Participants | 4 Participants |
| Race/Ethnicity, Customized Not Collected or Reported | 23 Participants | 5 Participants | 9 Participants | 4 Participants | 5 Participants |
| Race/Ethnicity, Customized Other (No classification) | 10 Participants | 2 Participants | 4 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 625 Participants | 158 Participants | 152 Participants | 165 Participants | 150 Participants |
| Sex: Female, Male Female | 346 Participants | 80 Participants | 92 Participants | 98 Participants | 76 Participants |
| Sex: Female, Male Male | 355 Participants | 95 Participants | 84 Participants | 78 Participants | 98 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 174 | 0 / 176 | 1 / 176 | 1 / 175 |
| other Total, other adverse events | 78 / 174 | 72 / 176 | 74 / 176 | 63 / 175 |
| serious Total, serious adverse events | 16 / 174 | 28 / 176 | 22 / 176 | 15 / 175 |
Outcome results
Primary
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
Population: ITT population; includes participants who had either completed that timepoint visit or discontinued at any time due to reasons other than study terminated by sponsor; the Non-responder Imputation (NRI)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | The Percentage of Participants Who Achieved a Clinical Remission at Week 12 | 25.0 Percentage of Participants |
| GED-0301 160 mg / GED-0301 40 mg 4 Week Alt | The Percentage of Participants Who Achieved a Clinical Remission at Week 12 | 25.3 Percentage of Participants |
| GED-0301 160 mg / GED-0301 40 mg | The Percentage of Participants Who Achieved a Clinical Remission at Week 12 | 21.3 Percentage of Participants |
| GED-0301 160 mg / GED-0301 160 mg 4 Week Alt | The Percentage of Participants Who Achieved a Clinical Remission at Week 12 | 21.7 Percentage of Participants |
p-value: 0.914195% CI: [-8.9, 10]Cochran-Mantel-Haenszel
p-value: 0.428695% CI: [-12.8, 5.6]Cochran-Mantel-Haenszel
p-value: 0.559195% CI: [-12, 6.6]Cochran-Mantel-Haenszel
Secondary
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
Population: ITT population; includes participants who had either completed that timepoint visit or discontinued at any time due to reasons other than study terminated by sponsor. NRI.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieved a Sustained Clinical Remission at Both Week 12 and 52 | 2.7 percentage of participants |
| GED-0301 160 mg / GED-0301 40 mg 4 Week Alt | Percentage of Participants Who Achieved a Sustained Clinical Remission at Both Week 12 and 52 | 2.5 percentage of participants |
| GED-0301 160 mg / GED-0301 40 mg | Percentage of Participants Who Achieved a Sustained Clinical Remission at Both Week 12 and 52 | 3.9 percentage of participants |
| GED-0301 160 mg / GED-0301 160 mg 4 Week Alt | Percentage of Participants Who Achieved a Sustained Clinical Remission at Both Week 12 and 52 | 1.7 percentage of participants |
p-value: 0.803195% CI: [-6.7, 5.9]Cochran-Mantel-Haenszel
p-value: 0.558395% CI: [-5.1, 7.3]Cochran-Mantel-Haenszel
p-value: 0.612395% CI: [-7.2, 6.8]Cochran-Mantel-Haenszel
Secondary
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
Population: ITT population; Includes participants who had either completed that timepoint visit or discontinued at any time due to reasons other than study terminated by sponsor. NRI.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieved Clinical Remission at Week 52 | 5.3 percentage of participants |
| GED-0301 160 mg / GED-0301 40 mg 4 Week Alt | Percentage of Participants Who Achieved Clinical Remission at Week 52 | 2.5 percentage of participants |
| GED-0301 160 mg / GED-0301 40 mg | Percentage of Participants Who Achieved Clinical Remission at Week 52 | 9.4 percentage of participants |
| GED-0301 160 mg / GED-0301 160 mg 4 Week Alt | Percentage of Participants Who Achieved Clinical Remission at Week 52 | 3.4 percentage of participants |
p-value: 0.252395% CI: [-9.7, 3.9]Cochran-Mantel-Haenszel
p-value: 0.162695% CI: [-3, 11.8]Cochran-Mantel-Haenszel
p-value: 0.44295% CI: [-9.1, 5.3]Cochran-Mantel-Haenszel
Secondary
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
Population: ITT population; includes participants who had either completed that timepoint visit or discontinued at any time due to reasons other than study terminated by sponsor. NRI.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Endoscopic Remission Centrally Read at Week 52 | 2.7 percentage of participants |
| GED-0301 160 mg / GED-0301 40 mg 4 Week Alt | Percentage of Participants With Endoscopic Remission Centrally Read at Week 52 | 0.8 percentage of participants |
| GED-0301 160 mg / GED-0301 40 mg | Percentage of Participants With Endoscopic Remission Centrally Read at Week 52 | 0.8 percentage of participants |
| GED-0301 160 mg / GED-0301 160 mg 4 Week Alt | Percentage of Participants With Endoscopic Remission Centrally Read at Week 52 | 0.9 percentage of participants |
p-value: 0.357395% CI: [-8.3, 5.9]Cochran-Mantel-Haenszel
p-value: 0.222195% CI: [-8.7, 5.1]Cochran-Mantel-Haenszel
p-value: 0.257895% CI: [-8.7, 5.6]Cochran-Mantel-Haenszel
Secondary
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
Population: ITT population; includes participants who had either completed that timepoint visit or discontinued at any time due to reasons other than study terminated by sponsor. NRI.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Endoscopic Response-25 Centrally Read at Week 12 | 28.1 percentage of participants |
| GED-0301 160 mg / GED-0301 40 mg 4 Week Alt | Percentage of Participants With Endoscopic Response-25 Centrally Read at Week 12 | 17.3 percentage of participants |
| GED-0301 160 mg / GED-0301 40 mg | Percentage of Participants With Endoscopic Response-25 Centrally Read at Week 12 | 27.4 percentage of participants |
| GED-0301 160 mg / GED-0301 160 mg 4 Week Alt | Percentage of Participants With Endoscopic Response-25 Centrally Read at Week 12 | 24.2 percentage of participants |
p-value: 0.023995% CI: [-19.6, -1.4]Cochran-Mantel-Haenszel
p-value: 0.833495% CI: [-10.8, 8.7]Cochran-Mantel-Haenszel
p-value: 0.438395% CI: [-13.5, 5.8]Cochran-Mantel-Haenszel
Secondary
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
Population: ITT population; Includes participants who had either completed that timepoint visit or discontinued at any time due to reasons other than study terminated by sponsor. NRI.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Endoscopic Response-50 Centrally Read at Week 52 | 3.5 percentage of participants |
| GED-0301 160 mg / GED-0301 40 mg 4 Week Alt | Percentage of Participants With Endoscopic Response-50 Centrally Read at Week 52 | 0.8 percentage of participants |
| GED-0301 160 mg / GED-0301 40 mg | Percentage of Participants With Endoscopic Response-50 Centrally Read at Week 52 | 1.6 percentage of participants |
| GED-0301 160 mg / GED-0301 160 mg 4 Week Alt | Percentage of Participants With Endoscopic Response-50 Centrally Read at Week 52 | 1.7 percentage of participants |
p-value: 0.179995% CI: [-9.5, 5]Cochran-Mantel-Haenszel
p-value: 0.230995% CI: [-9.4, 4.9]Cochran-Mantel-Haenszel
p-value: 0.326495% CI: [-9.1, 4.6]Cochran-Mantel-Haenszel
Secondary
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
Population: The safety population consisted of all participants who were randomized and received at least 1 dose of IP
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | The Number of Participants Who Discontinued IP Due to an Treatment Emergent Adverse Events | 11 participants |
| GED-0301 160 mg / GED-0301 40 mg 4 Week Alt | The Number of Participants Who Discontinued IP Due to an Treatment Emergent Adverse Events | 15 participants |
| GED-0301 160 mg / GED-0301 40 mg | The Number of Participants Who Discontinued IP Due to an Treatment Emergent Adverse Events | 16 participants |
| GED-0301 160 mg / GED-0301 160 mg 4 Week Alt | The Number of Participants Who Discontinued IP Due to an Treatment Emergent Adverse Events | 12 participants |
Secondary
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
Population: The safety population consisted of all participants who were randomized and received at least 1 dose of IP.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE) From Week 0 to Week 52 | Any Severe TEAE | 14 Participants |
| Placebo | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE) From Week 0 to Week 52 | Any TEAE Leading to Death | 0 Participants |
| Placebo | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE) From Week 0 to Week 52 | Any Serious IP-Related TEAE | 3 Participants |
| Placebo | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE) From Week 0 to Week 52 | Any Serious TEAE (SAE) | 16 Participants |
| Placebo | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE) From Week 0 to Week 52 | Any IP-Related TEAE | 31 Participants |
| Placebo | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE) From Week 0 to Week 52 | Any TEAE | 124 Participants |
| Placebo | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE) From Week 0 to Week 52 | Any TEAE Leading to IP Interruption | 4 Participants |
| Placebo | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE) From Week 0 to Week 52 | Any TEAE Leading to IP Withdrawal | 11 Participants |
| GED-0301 160 mg / GED-0301 40 mg 4 Week Alt | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE) From Week 0 to Week 52 | Any TEAE Leading to Death | 0 Participants |
| GED-0301 160 mg / GED-0301 40 mg 4 Week Alt | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE) From Week 0 to Week 52 | Any TEAE | 128 Participants |
| GED-0301 160 mg / GED-0301 40 mg 4 Week Alt | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE) From Week 0 to Week 52 | Any IP-Related TEAE | 35 Participants |
| GED-0301 160 mg / GED-0301 40 mg 4 Week Alt | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE) From Week 0 to Week 52 | Any Severe TEAE | 22 Participants |
| GED-0301 160 mg / GED-0301 40 mg 4 Week Alt | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE) From Week 0 to Week 52 | Any Serious TEAE (SAE) | 28 Participants |
| GED-0301 160 mg / GED-0301 40 mg 4 Week Alt | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE) From Week 0 to Week 52 | Any Serious IP-Related TEAE | 2 Participants |
| GED-0301 160 mg / GED-0301 40 mg 4 Week Alt | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE) From Week 0 to Week 52 | Any TEAE Leading to IP Withdrawal | 15 Participants |
| GED-0301 160 mg / GED-0301 40 mg 4 Week Alt | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE) From Week 0 to Week 52 | Any TEAE Leading to IP Interruption | 4 Participants |
| GED-0301 160 mg / GED-0301 40 mg | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE) From Week 0 to Week 52 | Any Severe TEAE | 21 Participants |
| GED-0301 160 mg / GED-0301 40 mg | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE) From Week 0 to Week 52 | Any Serious IP-Related TEAE | 2 Participants |
| GED-0301 160 mg / GED-0301 40 mg | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE) From Week 0 to Week 52 | Any TEAE Leading to IP Withdrawal | 16 Participants |
| GED-0301 160 mg / GED-0301 40 mg | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE) From Week 0 to Week 52 | Any IP-Related TEAE | 30 Participants |
| GED-0301 160 mg / GED-0301 40 mg | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE) From Week 0 to Week 52 | Any TEAE | 129 Participants |
| GED-0301 160 mg / GED-0301 40 mg | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE) From Week 0 to Week 52 | Any TEAE Leading to IP Interruption | 5 Participants |
| GED-0301 160 mg / GED-0301 40 mg | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE) From Week 0 to Week 52 | Any TEAE Leading to Death | 1 Participants |
| GED-0301 160 mg / GED-0301 40 mg | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE) From Week 0 to Week 52 | Any Serious TEAE (SAE) | 22 Participants |
| GED-0301 160 mg / GED-0301 160 mg 4 Week Alt | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE) From Week 0 to Week 52 | Any Severe TEAE | 15 Participants |
| GED-0301 160 mg / GED-0301 160 mg 4 Week Alt | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE) From Week 0 to Week 52 | Any TEAE Leading to Death | 1 Participants |
| GED-0301 160 mg / GED-0301 160 mg 4 Week Alt | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE) From Week 0 to Week 52 | Any Serious IP-Related TEAE | 0 Participants |
| GED-0301 160 mg / GED-0301 160 mg 4 Week Alt | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE) From Week 0 to Week 52 | Any IP-Related TEAE | 20 Participants |
| GED-0301 160 mg / GED-0301 160 mg 4 Week Alt | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE) From Week 0 to Week 52 | Any Serious TEAE (SAE) | 15 Participants |
| GED-0301 160 mg / GED-0301 160 mg 4 Week Alt | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE) From Week 0 to Week 52 | Any TEAE Leading to IP Interruption | 4 Participants |
| GED-0301 160 mg / GED-0301 160 mg 4 Week Alt | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE) From Week 0 to Week 52 | Any TEAE Leading to IP Withdrawal | 12 Participants |
| GED-0301 160 mg / GED-0301 160 mg 4 Week Alt | The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE) From Week 0 to Week 52 | Any TEAE | 113 Participants |
Secondary
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
Population: ITT population; includes participants who had either completed that timepoint visit or discontinued at any time due to reasons other than study terminated by sponsor. NRI.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | The Percentage of Participants Who Achieved a Clinical Remission at Week 4 | 20.1 percentage of participants |
| GED-0301 160 mg / GED-0301 40 mg 4 Week Alt | The Percentage of Participants Who Achieved a Clinical Remission at Week 4 | 18.6 percentage of participants |
| GED-0301 160 mg / GED-0301 40 mg | The Percentage of Participants Who Achieved a Clinical Remission at Week 4 | 16.5 percentage of participants |
| GED-0301 160 mg / GED-0301 160 mg 4 Week Alt | The Percentage of Participants Who Achieved a Clinical Remission at Week 4 | 15.4 percentage of participants |
p-value: 0.754195% CI: [-9.8, 7.1]Cochran-Mantel-Haenszel
p-value: 0.378495% CI: [-12, 4.6]Cochran-Mantel-Haenszel
p-value: 0.286595% CI: [-12.6, 3.8]Cochran-Mantel-Haenszel
Secondary
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
Population: ITT population; Includes participants who had either completed that timepoint visit or discontinued at any time due to reasons other than study terminated by sponsor. NRI.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | The Percentage of Participants Who Achieved a Clinical Response at Week 12 | 44.4 percentage of participants |
| GED-0301 160 mg / GED-0301 40 mg 4 Week Alt | The Percentage of Participants Who Achieved a Clinical Response at Week 12 | 32.1 percentage of participants |
| GED-0301 160 mg / GED-0301 40 mg | The Percentage of Participants Who Achieved a Clinical Response at Week 12 | 34.1 percentage of participants |
| GED-0301 160 mg / GED-0301 160 mg 4 Week Alt | The Percentage of Participants Who Achieved a Clinical Response at Week 12 | 33.8 percentage of participants |
p-value: 0.029995% CI: [-22, -1.1]Cochran-Mantel-Haenszel
p-value: 0.058295% CI: [-20.3, 0.7]Cochran-Mantel-Haenszel
p-value: 0.074195% CI: [-20.1, 1]Cochran-Mantel-Haenszel
Secondary
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
Population: ITT Population; includes participants who had either completed that timepoint visit or discontinued at any time due to reasons other than study terminated by sponsor. NRI.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | The Percentage of Participants Who Achieved a Clinical Response at Week 4 | 34.3 percentage of participants |
| GED-0301 160 mg / GED-0301 40 mg 4 Week Alt | The Percentage of Participants Who Achieved a Clinical Response at Week 4 | 28.5 percentage of participants |
| GED-0301 160 mg / GED-0301 40 mg | The Percentage of Participants Who Achieved a Clinical Response at Week 4 | 32.4 percentage of participants |
| GED-0301 160 mg / GED-0301 160 mg 4 Week Alt | The Percentage of Participants Who Achieved a Clinical Response at Week 4 | 27.8 percentage of participants |
p-value: 0.249395% CI: [-15.5, 4]Cochran-Mantel-Haenszel
p-value: 0.71695% CI: [-11.8, 8.2]Cochran-Mantel-Haenszel
p-value: 0.245295% CI: [-15.5, 4.1]Cochran-Mantel-Haenszel
Secondary
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
Population: ITT population; includes participants who received oral corticosteroids at baseline and had either completed that timepoint visit or discontinued at any time due to reasons other than study terminated by sponsor. NRI.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | The Percentage of Participants Who Achieved a Corticosteroid-Free Clinical Remission at Week 52 | 2.2 percentage of participants |
| GED-0301 160 mg / GED-0301 40 mg 4 Week Alt | The Percentage of Participants Who Achieved a Corticosteroid-Free Clinical Remission at Week 52 | 0.0 percentage of participants |
| GED-0301 160 mg / GED-0301 40 mg | The Percentage of Participants Who Achieved a Corticosteroid-Free Clinical Remission at Week 52 | 7.0 percentage of participants |
| GED-0301 160 mg / GED-0301 160 mg 4 Week Alt | The Percentage of Participants Who Achieved a Corticosteroid-Free Clinical Remission at Week 52 | 2.4 percentage of participants |
Comparison: 2-sided 95% CI were based on the unstratified Newcombe method.p-value: 0.357295% CI: [-11.3, 7]Cochran-Mantel-Haenszel
p-value: 0.282395% CI: [-8.8, 18.9]Cochran-Mantel-Haenszel
p-value: >0.999995% CI: [-12.8, 13.7]Cochran-Mantel-Haenszel