Crohn Disease
Conditions
Keywords
Crohn's Disease, infliximab, azathioprine, Remicade, SONIC
Brief summary
The purpose of this study is to assess the safety and effectiveness of three different treatments for patients with Crohns disease who have not responded to previous treatment with a group of drugs commonly used to treat Crohn's Disease (5-ASA) and corticosteroids. Patients will receive either infliximab (a drug used to treat autoimmune diseases) or azathioprine (an immunosuppressant or drug used to suppress the immune system) or a combination of both for up to 34 weeks. This research study will involve approximately 500 patients. The main study involves up to 34 weeks (approximately 8 months). A study extension of an additional 20 weeks (approximately 5 months) is optional for patients who successfully complete the main study. A country-specific study extension of open label infliximab treatment for an additional 1 year is optional for patients who successfully complete the main study extension.
Detailed description
Crohns disease is characterized by inflammation (the changes that happen when tissues in the body are injured) and ulceration (open sores) of the intestines. Crohns disease is treated with medications that decrease inflammation, and reduce diarrhea, abdominal pain and other symptoms of Crohns disease. In addition, Crohns disease can be treated with medications that suppress the immune system (the body system involved in inflammation and infections) or with surgery. This study will investigate the effectiveness of infliximab and azathioprine in the treatment of patients with moderate-to-severe Crohns disease. Infliximab is currently approved by the FDA for the treatment of both Crohns disease and rheumatoid arthritis. Azathioprine, which is an investigational drug, has not been approved by the FDA for the treatment of Crohns disease, but it is a well-established therapy that has been used for many years to treat Crohns disease. This study seeks to determine whether infliximab, azathioprine, or the combination of both drugs would be the most appropriate treatment for Crohns disease patients who have not responded well to certain drugs called 5-ASA drugs (e.g. Asacol, Pentasa, sulfasalazine) and/or require frequent treatment with corticosteroids. This research study will involve approximately 500 patients. Patients may participate in the main study for up to 34 weeks (approximately 8 months). During the main study, patients will be asked to visit the study center for 10 visits. If patients enroll into the extension of the study, the total time for participation may be up to 54 weeks (approximately 13 months). Patients enrolled in the Study Extension will be asked to visit the study center for an additional 5 visits. A country-specific (EU and Israel only), prospective, multi-center, open-label extension of the study will further evaluate the long-term safety and efficacy of scheduled maintenance therapy with infliximab in patients with Crohns Disease. Patients who have completed treatment through Week 50 in the SONIC main study and who, in the opinion of the investigator, would benefit from infliximab treatment may enter the open-label extension. Patients will be randomly assigned to one of three treatment groups (either infliximab plus placebo capsules, infliximab plus azathioprine, or azathioprine plus placebo infusions - there is no possibility of being assigned to placebo only in this trial - patients will receive one or both of these medications) at the beginning of the study. Oral medication will be taken daily. There are 5 infusion (which will be either infliximab or placebo) visits during the main study.
Interventions
BIOLOGICALinfliximab infusion; AZA placebo caps
Infliximab 5 mg/kg at weeks 0, 2, 6, 14, and 22 and placebo AZA capsules
OTHERinfliximab (IFX) infusion; azathioprine (AZA) caps
AZA daily 2.5 mg/kg/day and IFX infusions 5 mg/kg at weeks 0, 2, 6, 14, and 22
DRUGinfliximab (IFX) placebo infusion; azathioprine (AZA) caps
AZA daily 2.5 mg/kg/day and placebo IFX infusions at weeks 0, 2, 6, 14, and 22
Sponsors
Schering-Plough
Centocor Ortho Biotech Services, L.L.C.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of Crohns Disease for at least 6 weeks * Moderate to severe disease activity (CDAI \>= 220 and \<=450) * No history of azathioprine, 6-MP (6 Mercaptopurine), or biologic treatments * Are either: Corticosteriod-dependent, OR considered for a 2nd (or greater) course of corticosteriod, OR 5-ASA failures, Or Budesonide failures
Exclusion criteria
* History of abdominal surgery within the last 6 months * Have an ostomy or stoma \[An operation to create an opening from an area inside the body to the outside\] * Are pregnant, nursing, or planning pregnancy (both men and women) * Serious simultaneous illness that could interfere with study participation * Use of any investigational drug within 30 days * Have a concomitant diagnosis or any history of congestive heart failure * Weigh more than 140 kilograms (or 310 pounds)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Corticosteriod-free Clinical Remission | Week 26 | Corticosteroid-free clinical remission is defined as a Crohn's Disease Activity Index (CDAI) less than (\<) 150 in participants who have not received any dose of systemic corticosteroids (prednisone or equivalent) for greater than or equal to (\>=) 3 weeks and have not received budesonide at a dose \> 6 milligram per day (mg/day) for \>= 3 weeks. The total CDAI score ranges from 0 - 600. The lower the CDAI score, the better (i.e., 0 is better and 600 is worse). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Corticosteroid-free Clinical Remission (Study Extension) | Week 50 | Corticosteroid-free clinical remission is defined as a Crohn's Disease Activity Index (CDAI) \< 150 who have not received any dose of systemic corticosteroids (prednisone or equivalent) for \>= 3 weeks and have not received budesonide at a dose \> 6 milligram per day (mg/day) for \>= 3 weeks. The total CDAI score ranges from 0 - 600. The lower the CDAI score, the better (i.e., 0 is better and 600 is worse). |
| Percentage of Participants With Clinical Remission (Main Study) | Weeks 2, 6, 10, 18 and 26 | Clinical remission is defined as a CDAI \< 150, compared to baseline (Week 0) |
| Percentage of Participants With Clinical Remission (Study Extension) | Weeks 34, 42 and 50 | Clinical remission is defined as a CDAI \< 150, compared to baseline (Week 0) |
| Percentage of Participants With Mucosal Healing | Week 26 | Complete absence of mucosal ulcerations in the colon and terminal ileum as assessed by video endoscopy. |
| Percentage of Participants With Clinical Response Over Time (Study Extension) | Weeks 34, 42, 50 | Clinical response, defined as a \>=100-point decrease in CDAI from Baseline. |
| Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Weeks 2, 6, 10, 18 and 26 (Main Study) | Baseline and Weeks 2, 6, 10, 18, 26 | Quality of life as measured by the Inflammatory Bowel Disease Questionnaire (IBDQ). The IBDQ is a 32- item questionnaire and the total IBDQ score can range from 32 (very poor) to 224 (perfect). |
| Average Corticosteroid Use | Weeks 2, 6, 10, 18 and 26 | Average daily dose of systemic corticosteroid concomitant medications(prednisone or equivalent) |
| Percentage of Participants With Clinical Response Over Time (Main Study) | Weeks 2, 6, 10, 18, 26 | Clinical response, defined as a \>=100-point decrease in CDAI from Baseline. |
Countries
Austria, Belgium, Canada, Denmark, France, Germany, Greece, Israel, Netherlands, Norway, Portugal, Spain, Sweden, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Azathioprine + Placebo Participants received placebo (PBO) infusions and daily Azathioprine (AZA) capsules in main study through Week 30. Participants who completed treatment in the main study and in the opinion of investigator, had benefited from continued treatment were entered in the study extension and received same assigned treatments (which they were receiving in main study) from Week 30 to 46. Those who completed treatment in the study extension may enter in country specific (EU and Israel) OLE. | 170 |
| Infliximab + Placebo Participants received infliximab (IFX) infusions 5 mg/kg body weight of participant along with placebo capsules daily in main study through Week 30. Participants who completed treatment in the main study and, in the opinion of investigator, had benefited from continued treatment were entered in the study extension and received same assigned treatments (which they were receiving in main study) from Week 30 to 46. Those who completed treatment in the study extension may enter in country specific (EU and Israel) OLE. | 169 |
| Infliximab + Azathioprine Participants received infliximab infusions 5 mg/kg body weight of participant along with daily AZA capsules 2.5 mg/kg body weight of participant in main study through Week 30. Participants who completed treatment in the main study and, in the opinion of investigator, had benefited from continued treatment were entered in the study extension and received same assigned treatments (which they were receiving in main study) from Week 30 to 46. Those who completed treatment in the study extension may enter in country specific (EU and Israel) OLE. | 169 |
| Total | 508 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Main Study: Through Week 30 | Adverse Event | 38 | 20 | 28 | 0 | 0 | 0 |
| Main Study: Through Week 30 | Death | 1 | 0 | 0 | 0 | 0 | 0 |
| Main Study: Through Week 30 | Eligibility criteria not met | 3 | 8 | 2 | 0 | 0 | 0 |
| Main Study: Through Week 30 | Lost to Follow-up | 5 | 5 | 2 | 0 | 0 | 0 |
| Main Study: Through Week 30 | Other | 19 | 16 | 9 | 0 | 0 | 0 |
| Main Study: Through Week 30 | Withdrawal by Subject | 18 | 9 | 7 | 0 | 0 | 0 |
| OLE: Open-Label Extension | Adverse Event | 0 | 0 | 0 | 0 | 3 | 4 |
| OLE: Open-Label Extension | Inadequate therapeutic effect | 0 | 0 | 0 | 1 | 1 | 0 |
| OLE: Open-Label Extension | Patient decision | 0 | 0 | 0 | 0 | 1 | 0 |
| Study Extension: Week 30 Through Week 50 | Adverse Event | 3 | 9 | 7 | 0 | 0 | 0 |
| Study Extension: Week 30 Through Week 50 | Lost to Follow-up | 2 | 1 | 4 | 0 | 0 | 0 |
| Study Extension: Week 30 Through Week 50 | Other | 1 | 2 | 3 | 0 | 0 | 0 |
| Study Extension: Week 30 Through Week 50 | Withdrawal by Subject | 2 | 0 | 4 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Azathioprine + Placebo | Infliximab + Placebo | Infliximab + Azathioprine | Total |
|---|---|---|---|---|
| Age, Continuous | 36.3 years STANDARD_DEVIATION 12.92 | 36.6 years STANDARD_DEVIATION 13 | 35.9 years STANDARD_DEVIATION 11.97 | 36.3 years STANDARD_DEVIATION 12.62 |
| Gender Female | 80 Participants | 85 Participants | 81 Participants | 246 Participants |
| Gender Male | 90 Participants | 84 Participants | 88 Participants | 262 Participants |
| Region of Enrollment AUSTRIA | 8 participants | 9 participants | 8 participants | 25 participants |
| Region of Enrollment BELGIUM | 14 participants | 17 participants | 15 participants | 46 participants |
| Region of Enrollment CANADA | 9 participants | 7 participants | 7 participants | 23 participants |
| Region of Enrollment DENMARK | 5 participants | 8 participants | 4 participants | 17 participants |
| Region of Enrollment FRANCE | 9 participants | 12 participants | 18 participants | 39 participants |
| Region of Enrollment GERMANY | 17 participants | 8 participants | 13 participants | 38 participants |
| Region of Enrollment GREECE | 3 participants | 3 participants | 3 participants | 9 participants |
| Region of Enrollment ISRAEL | 7 participants | 13 participants | 12 participants | 32 participants |
| Region of Enrollment NETHERLANDS | 9 participants | 9 participants | 8 participants | 26 participants |
| Region of Enrollment NORWAY | 0 participants | 1 participants | 0 participants | 1 participants |
| Region of Enrollment PORTUGAL | 0 participants | 2 participants | 0 participants | 2 participants |
| Region of Enrollment SPAIN | 2 participants | 2 participants | 2 participants | 6 participants |
| Region of Enrollment SWEDEN | 0 participants | 1 participants | 2 participants | 3 participants |
| Region of Enrollment UK | 4 participants | 11 participants | 7 participants | 22 participants |
| Region of Enrollment USA | 83 participants | 66 participants | 70 participants | 219 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 120 / 161 | 122 / 163 | 133 / 179 | 44 / 75 | 69 / 97 | 61 / 108 | 7 / 8 | 16 / 18 | 15 / 17 |
| serious Total, serious adverse events | 39 / 161 | 26 / 163 | 25 / 179 | 5 / 75 | 15 / 97 | 2 / 108 | 1 / 8 | 1 / 18 | 3 / 17 |
Outcome results
Primary
Percentage of Participants With Corticosteriod-free Clinical Remission
Corticosteroid-free clinical remission is defined as a Crohn's Disease Activity Index (CDAI) less than (\<) 150 in participants who have not received any dose of systemic corticosteroids (prednisone or equivalent) for greater than or equal to (\>=) 3 weeks and have not received budesonide at a dose \> 6 milligram per day (mg/day) for \>= 3 weeks. The total CDAI score ranges from 0 - 600. The lower the CDAI score, the better (i.e., 0 is better and 600 is worse).
Time frame: Week 26
Population: Intention to treat (ITT) population includes all randomized participants in the analysis, according to the treatment group to which they were randomized, regardless of the treatment they actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Azathioprine + Placebo | Percentage of Participants With Corticosteriod-free Clinical Remission | 30.0 percentage of participants |
| Infliximab + Placebo | Percentage of Participants With Corticosteriod-free Clinical Remission | 44.4 percentage of participants |
| Infliximab + Azathioprine | Percentage of Participants With Corticosteriod-free Clinical Remission | 56.8 percentage of participants |
p-value: <0.001Cochran-Mantel-Haenszel
p-value: 0.006Cochran-Mantel-Haenszel
p-value: 0.022Cochran-Mantel-Haenszel
Secondary
Average Corticosteroid Use
Average daily dose of systemic corticosteroid concomitant medications(prednisone or equivalent)
Time frame: Weeks 2, 6, 10, 18 and 26
Population: Population analyzed included all randomized participants taking corticosteroids for Crohn's disease. n' signifies number of participants who were evaluable at specified time point, for each arm respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Azathioprine + Placebo | Average Corticosteroid Use | Week 18 (n=59, 57, 56) | 13.49 milligram per day | Standard Deviation 10.929 |
| Azathioprine + Placebo | Average Corticosteroid Use | Week 10 (n=56, 56, 52) | 16.19 milligram per day | Standard Deviation 11.16 |
| Azathioprine + Placebo | Average Corticosteroid Use | Week 2 (n=48, 50, 49) | 22.92 milligram per day | Standard Deviation 12.476 |
| Azathioprine + Placebo | Average Corticosteroid Use | Week 6 (n=53, 52, 51) | 18.56 milligram per day | Standard Deviation 11.588 |
| Azathioprine + Placebo | Average Corticosteroid Use | Week 26 (n=60, 60, 58) | 11.57 milligram per day | Standard Deviation 10.246 |
| Infliximab + Placebo | Average Corticosteroid Use | Week 10 (n=56, 56, 52) | 15.68 milligram per day | Standard Deviation 14.924 |
| Infliximab + Placebo | Average Corticosteroid Use | Week 2 (n=48, 50, 49) | 21.20 milligram per day | Standard Deviation 11.883 |
| Infliximab + Placebo | Average Corticosteroid Use | Week 6 (n=53, 52, 51) | 17.68 milligram per day | Standard Deviation 10.993 |
| Infliximab + Placebo | Average Corticosteroid Use | Week 18 (n=59, 57, 56) | 13.23 milligram per day | Standard Deviation 17.206 |
| Infliximab + Placebo | Average Corticosteroid Use | Week 26 (n=60, 60, 58) | 10.96 milligram per day | Standard Deviation 15.99 |
| Infliximab + Azathioprine | Average Corticosteroid Use | Week 26 (n=60, 60, 58) | 9.35 milligram per day | Standard Deviation 10.052 |
| Infliximab + Azathioprine | Average Corticosteroid Use | Week 18 (n=59, 57, 56) | 11.64 milligram per day | Standard Deviation 10.904 |
| Infliximab + Azathioprine | Average Corticosteroid Use | Week 2 (n=48, 50, 49) | 22.75 milligram per day | Standard Deviation 11.923 |
| Infliximab + Azathioprine | Average Corticosteroid Use | Week 10 (n=56, 56, 52) | 15.01 milligram per day | Standard Deviation 11.087 |
| Infliximab + Azathioprine | Average Corticosteroid Use | Week 6 (n=53, 52, 51) | 18.26 milligram per day | Standard Deviation 11.635 |
Secondary
Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Weeks 2, 6, 10, 18 and 26 (Main Study)
Quality of life as measured by the Inflammatory Bowel Disease Questionnaire (IBDQ). The IBDQ is a 32- item questionnaire and the total IBDQ score can range from 32 (very poor) to 224 (perfect).
Time frame: Baseline and Weeks 2, 6, 10, 18, 26
Population: Population analyzed included all randomized participants enrolled in Main Study with last observation carried forward method to impute missing data. 'n' signifies number of participants who were evaluable at specified time point, for each arm respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Azathioprine + Placebo | Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Weeks 2, 6, 10, 18 and 26 (Main Study) | Week 18 (n= 162, 161, 165) | 30.3 units on a scale | Standard Deviation 33.92 |
| Azathioprine + Placebo | Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Weeks 2, 6, 10, 18 and 26 (Main Study) | Week 10 (n= 162, 161, 165) | 31.0 units on a scale | Standard Deviation 31.66 |
| Azathioprine + Placebo | Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Weeks 2, 6, 10, 18 and 26 (Main Study) | Week 2 (n= 160, 160, 163) | 20.1 units on a scale | Standard Deviation 24.29 |
| Azathioprine + Placebo | Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Weeks 2, 6, 10, 18 and 26 (Main Study) | Week 6 (n= 162, 161, 165) | 28.3 units on a scale | Standard Deviation 31.25 |
| Azathioprine + Placebo | Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Weeks 2, 6, 10, 18 and 26 (Main Study) | Week 26 (n= 162, 161, 165) | 31.4 units on a scale | Standard Deviation 35.43 |
| Infliximab + Placebo | Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Weeks 2, 6, 10, 18 and 26 (Main Study) | Week 10 (n= 162, 161, 165) | 37.8 units on a scale | Standard Deviation 35.56 |
| Infliximab + Placebo | Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Weeks 2, 6, 10, 18 and 26 (Main Study) | Week 2 (n= 160, 160, 163) | 27.7 units on a scale | Standard Deviation 26.08 |
| Infliximab + Placebo | Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Weeks 2, 6, 10, 18 and 26 (Main Study) | Week 6 (n= 162, 161, 165) | 34.8 units on a scale | Standard Deviation 31.79 |
| Infliximab + Placebo | Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Weeks 2, 6, 10, 18 and 26 (Main Study) | Week 18 (n= 162, 161, 165) | 39.9 units on a scale | Standard Deviation 34.17 |
| Infliximab + Placebo | Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Weeks 2, 6, 10, 18 and 26 (Main Study) | Week 26 (n= 162, 161, 165) | 39.9 units on a scale | Standard Deviation 36.62 |
| Infliximab + Azathioprine | Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Weeks 2, 6, 10, 18 and 26 (Main Study) | Week 26 (n= 162, 161, 165) | 45.2 units on a scale | Standard Deviation 35.76 |
| Infliximab + Azathioprine | Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Weeks 2, 6, 10, 18 and 26 (Main Study) | Week 18 (n= 162, 161, 165) | 43.7 units on a scale | Standard Deviation 34.56 |
| Infliximab + Azathioprine | Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Weeks 2, 6, 10, 18 and 26 (Main Study) | Week 2 (n= 160, 160, 163) | 31.4 units on a scale | Standard Deviation 29.6 |
| Infliximab + Azathioprine | Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Weeks 2, 6, 10, 18 and 26 (Main Study) | Week 10 (n= 162, 161, 165) | 42.4 units on a scale | Standard Deviation 34.67 |
| Infliximab + Azathioprine | Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Weeks 2, 6, 10, 18 and 26 (Main Study) | Week 6 (n= 162, 161, 165) | 39.9 units on a scale | Standard Deviation 32.9 |
Secondary
Percentage of Participants With Clinical Remission (Main Study)
Clinical remission is defined as a CDAI \< 150, compared to baseline (Week 0)
Time frame: Weeks 2, 6, 10, 18 and 26
Population: Population analyzed included all randomized participants enrolled in the main study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Azathioprine + Placebo | Percentage of Participants With Clinical Remission (Main Study) | Week 18 | 33.5 percentage of participants |
| Azathioprine + Placebo | Percentage of Participants With Clinical Remission (Main Study) | Week 10 | 34.1 percentage of participants |
| Azathioprine + Placebo | Percentage of Participants With Clinical Remission (Main Study) | Week 2 | 17.6 percentage of participants |
| Azathioprine + Placebo | Percentage of Participants With Clinical Remission (Main Study) | Week 6 | 27.6 percentage of participants |
| Azathioprine + Placebo | Percentage of Participants With Clinical Remission (Main Study) | Week 26 | 31.8 percentage of participants |
| Infliximab + Placebo | Percentage of Participants With Clinical Remission (Main Study) | Week 10 | 47.3 percentage of participants |
| Infliximab + Placebo | Percentage of Participants With Clinical Remission (Main Study) | Week 2 | 32.5 percentage of participants |
| Infliximab + Placebo | Percentage of Participants With Clinical Remission (Main Study) | Week 6 | 49.1 percentage of participants |
| Infliximab + Placebo | Percentage of Participants With Clinical Remission (Main Study) | Week 18 | 49.7 percentage of participants |
| Infliximab + Placebo | Percentage of Participants With Clinical Remission (Main Study) | Week 26 | 47.9 percentage of participants |
| Infliximab + Azathioprine | Percentage of Participants With Clinical Remission (Main Study) | Week 26 | 60.4 percentage of participants |
| Infliximab + Azathioprine | Percentage of Participants With Clinical Remission (Main Study) | Week 18 | 60.4 percentage of participants |
| Infliximab + Azathioprine | Percentage of Participants With Clinical Remission (Main Study) | Week 2 | 36.7 percentage of participants |
| Infliximab + Azathioprine | Percentage of Participants With Clinical Remission (Main Study) | Week 10 | 59.8 percentage of participants |
| Infliximab + Azathioprine | Percentage of Participants With Clinical Remission (Main Study) | Week 6 | 52.1 percentage of participants |
Secondary
Percentage of Participants With Clinical Remission (Study Extension)
Clinical remission is defined as a CDAI \< 150, compared to baseline (Week 0)
Time frame: Weeks 34, 42 and 50
Population: Population analyzed included all randomized participants enrolled in the Study Extension.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Azathioprine + Placebo | Percentage of Participants With Clinical Remission (Study Extension) | Week 42 | 58.7 percentage of participants |
| Azathioprine + Placebo | Percentage of Participants With Clinical Remission (Study Extension) | Week 34 | 61.3 percentage of participants |
| Azathioprine + Placebo | Percentage of Participants With Clinical Remission (Study Extension) | Week 50 | 54.7 percentage of participants |
| Infliximab + Placebo | Percentage of Participants With Clinical Remission (Study Extension) | Week 42 | 72.2 percentage of participants |
| Infliximab + Placebo | Percentage of Participants With Clinical Remission (Study Extension) | Week 34 | 66.0 percentage of participants |
| Infliximab + Placebo | Percentage of Participants With Clinical Remission (Study Extension) | Week 50 | 66.0 percentage of participants |
| Infliximab + Azathioprine | Percentage of Participants With Clinical Remission (Study Extension) | Week 34 | 69.4 percentage of participants |
| Infliximab + Azathioprine | Percentage of Participants With Clinical Remission (Study Extension) | Week 50 | 74.1 percentage of participants |
| Infliximab + Azathioprine | Percentage of Participants With Clinical Remission (Study Extension) | Week 42 | 73.1 percentage of participants |
Secondary
Percentage of Participants With Clinical Response Over Time (Main Study)
Clinical response, defined as a \>=100-point decrease in CDAI from Baseline.
Time frame: Weeks 2, 6, 10, 18, 26
Population: Population analyzed included all randomized participants during the Main Study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Azathioprine + Placebo | Percentage of Participants With Clinical Response Over Time (Main Study) | Week 26 | 37.6 percentage of participants |
| Azathioprine + Placebo | Percentage of Participants With Clinical Response Over Time (Main Study) | Week 10 | 39.4 percentage of participants |
| Azathioprine + Placebo | Percentage of Participants With Clinical Response Over Time (Main Study) | Week 6 | 37.6 percentage of participants |
| Azathioprine + Placebo | Percentage of Participants With Clinical Response Over Time (Main Study) | Week 18 | 38.8 percentage of participants |
| Azathioprine + Placebo | Percentage of Participants With Clinical Response Over Time (Main Study) | Week 2 | 22.4 percentage of participants |
| Infliximab + Placebo | Percentage of Participants With Clinical Response Over Time (Main Study) | Week 18 | 55.0 percentage of participants |
| Infliximab + Placebo | Percentage of Participants With Clinical Response Over Time (Main Study) | Week 2 | 42.6 percentage of participants |
| Infliximab + Placebo | Percentage of Participants With Clinical Response Over Time (Main Study) | Week 6 | 54.4 percentage of participants |
| Infliximab + Placebo | Percentage of Participants With Clinical Response Over Time (Main Study) | Week 10 | 55.6 percentage of participants |
| Infliximab + Placebo | Percentage of Participants With Clinical Response Over Time (Main Study) | Week 26 | 54.4 percentage of participants |
| Infliximab + Azathioprine | Percentage of Participants With Clinical Response Over Time (Main Study) | Week 18 | 62.7 percentage of participants |
| Infliximab + Azathioprine | Percentage of Participants With Clinical Response Over Time (Main Study) | Week 6 | 63.3 percentage of participants |
| Infliximab + Azathioprine | Percentage of Participants With Clinical Response Over Time (Main Study) | Week 2 | 47.3 percentage of participants |
| Infliximab + Azathioprine | Percentage of Participants With Clinical Response Over Time (Main Study) | Week 26 | 62.1 percentage of participants |
| Infliximab + Azathioprine | Percentage of Participants With Clinical Response Over Time (Main Study) | Week 10 | 69.2 percentage of participants |
Secondary
Percentage of Participants With Clinical Response Over Time (Study Extension)
Clinical response, defined as a \>=100-point decrease in CDAI from Baseline.
Time frame: Weeks 34, 42, 50
Population: Population analyzed included all randomized participants during the Study Extension.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Azathioprine + Placebo | Percentage of Participants With Clinical Response Over Time (Study Extension) | Week 42 | 65.3 percentage of participants |
| Azathioprine + Placebo | Percentage of Participants With Clinical Response Over Time (Study Extension) | Week 34 | 66.7 percentage of participants |
| Azathioprine + Placebo | Percentage of Participants With Clinical Response Over Time (Study Extension) | Week 50 | 62.7 percentage of participants |
| Infliximab + Placebo | Percentage of Participants With Clinical Response Over Time (Study Extension) | Week 42 | 74.2 percentage of participants |
| Infliximab + Placebo | Percentage of Participants With Clinical Response Over Time (Study Extension) | Week 34 | 76.3 percentage of participants |
| Infliximab + Placebo | Percentage of Participants With Clinical Response Over Time (Study Extension) | Week 50 | 72.2 percentage of participants |
| Infliximab + Azathioprine | Percentage of Participants With Clinical Response Over Time (Study Extension) | Week 34 | 76.9 percentage of participants |
| Infliximab + Azathioprine | Percentage of Participants With Clinical Response Over Time (Study Extension) | Week 50 | 78.7 percentage of participants |
| Infliximab + Azathioprine | Percentage of Participants With Clinical Response Over Time (Study Extension) | Week 42 | 77.8 percentage of participants |
Secondary
Percentage of Participants With Corticosteroid-free Clinical Remission (Study Extension)
Corticosteroid-free clinical remission is defined as a Crohn's Disease Activity Index (CDAI) \< 150 who have not received any dose of systemic corticosteroids (prednisone or equivalent) for \>= 3 weeks and have not received budesonide at a dose \> 6 milligram per day (mg/day) for \>= 3 weeks. The total CDAI score ranges from 0 - 600. The lower the CDAI score, the better (i.e., 0 is better and 600 is worse).
Time frame: Week 50
Population: Population analyzed included all randomized participants enrolled in Study Extension.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Azathioprine + Placebo | Percentage of Participants With Corticosteroid-free Clinical Remission (Study Extension) | 54.7 percentage of participants |
| Infliximab + Placebo | Percentage of Participants With Corticosteroid-free Clinical Remission (Study Extension) | 60.8 percentage of participants |
| Infliximab + Azathioprine | Percentage of Participants With Corticosteroid-free Clinical Remission (Study Extension) | 72.2 percentage of participants |
Secondary
Percentage of Participants With Mucosal Healing
Complete absence of mucosal ulcerations in the colon and terminal ileum as assessed by video endoscopy.
Time frame: Week 26
Population: Analysis population for mucosal healing was per protocol. All subjects with lesions at Baseline (Week 0) and an Endoscopy at Week 26 were included in the analysis. Here, 'N' \[number of participants analyzed\] signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Azathioprine + Placebo | Percentage of Participants With Mucosal Healing | 16.5 percentage of participants |
| Infliximab + Placebo | Percentage of Participants With Mucosal Healing | 30.1 percentage of participants |
| Infliximab + Azathioprine | Percentage of Participants With Mucosal Healing | 43.9 percentage of participants |
p-value: <0.001Cochran-Mantel-Haenszel
p-value: 0.023Cochran-Mantel-Haenszel
p-value: 0.055Cochran-Mantel-Haenszel