Crohn's Disease
Conditions
Keywords
IBD, Crohn's Disease
Brief summary
The primary objective of this study is to evaluate the efficacy of abrilumab as measured by the proportion of participants achieving Crohn's Disease Activity Index (CDAI) remission (CDAI \< 150) after treatment for 8 weeks.
Detailed description
The study consisted of a 24-week double-blind treatment period, a 108-week open-label treatment period, and a 2-year safety follow-up period. Participants who did not reach minimal improvement, or experienced disease worsening after initial response, had the option to receive open-label abrilumab 210 mg every 3 months (Q3M) beginning at double-blind period week 12 or after. Not reaching minimal improvement was defined as not having an improvement in CDAI score of ≥ 70 points from baseline on 2 consecutive visits (at or after week 8) at least 2 weeks apart. Disease worsening after week 8 (or week 12) response was defined as having an increase in CDAI score of ≥ 70 points from the week 8 (or week 12) CDAI score on 2 consecutive visits at least 2 weeks apart, and a CDAI score of \> 150. Participants were planned to be randomized in a 2:1:2:1 ratio to SC placebo or abrilumab at 21 mg, 70 mg (on day 1, week 2, week 4, and every 4 weeks thereafter until week 24), or 210 mg (on day 1 followed by placebo in weeks 2 and 4 and every 4 weeks thereafter until week 24), respectively. Due to a consistent discrepancy between the investigational product (IP) instruction manual (IPIM) description of vial positions and the actual vial positions in the IP package participants were initially randomized to 3 arms (placebo, 70 mg, and 210 mg) with a randomization ratio of 3:2:1. The study was temporarily paused while this issue was investigated. Once the discrepancy was corrected, Protocol Amendment 3 implemented, and affected participants completed their double-blind treatment period, the study resumed enrollment and randomization per protocol. Neither the randomization nor study blind was compromised and therefore the intent-to-treat principle was maintained.
Interventions
DRUGAbrilumab
Administered by subcutaneous injection.
DRUGPlacebo
Placebo matching to abrilumab administered by subcutaneous injection
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosed with ileal, ileo-colonic, or colonic Crohn's disease for a minimum of 6 months prior to baseline * Moderately to severely active Crohn's disease defined by a CDAI score ≥ 220 and ≤ 450 at baseline * Evidence of active inflammation within 12 weeks prior to baseline * Demonstrated an inadequate response to, loss of response to, or intolerance to at least one of the following agents: Immunomodulators and/or anti-tumor necrosis factor (TNF) agents or to corticosteroids (non-US sites only). * Neurological exam free of clinically significant, unexplained signs or symptoms during screening and no clinically significant change prior to randomization * Subject has no known history of active tuberculosis and has a negative test for tuberculosis during screening
Exclusion criteria
* Short bowel syndrome * Stricture with obstructive symptoms within 3 months * Bowel surgery within 12 weeks prior baseline, or has planned bowel surgery within 24 weeks from baseline * Ileostomy and/or colostomy * Any gastric or intestinal pouch * Evidence of an infected abscess * Bowel perforation or evidence of non-inflammatory obstruction during the 6 months prior to baseline * Stool positive for C. difficile toxin at screening * Any uncontrolled or clinically significant systemic disease * Known to have tested positive for hepatitis B virus surface antigen, hepatitis C virus antibody, or human immunodeficiency virus (HIV) * Any underlying condition that predisposes subject to infections * Subject has malignancy (other than resected cutaneous basal or cutaneous squamous cell carcinoma, or treated in situ cervical cancer considered cured) within 5 years of baseline * Received an anti-TNF agent, cyclosporine, mycophenolate mofetil, sirolimus (rapamycin), thalidomide, tacrolimus, topical (rectal) aminosalicylic acid (eg, mesalamine) or topical (rectal) steroids, intravenous or intramuscular corticosteroids within protocol-specified time periods. * Any prior exposure to antagonists of integrins or integrin ligands (eg, natalizumab, efalizumab, or vedolizumab), rituximab, or TNF kinoid immunotherapies, AMG 181, or any form of cell-based transplantation * Received treatment of infection with intravenous (within 30 days of baseline) or oral (within 14 days prior to baseline) antibiotics, antivirals, or antifungals * Significant laboratory abnormalities * Pregnant or breast feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Remission at Week 8 | Week 8 | Remission was defined as a Crohn's Disease Activity Index (CDAI) score \< 150 at week 8. The CDAI is a weighted, composite index of 8 disease variables (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extra-intestinal manifestations or fistula, use or non-use of antidiarrheal agents, presence or absence of an abdominal mass, hematocrit, and body weight). Scores range from approximately 0 to 600, with a higher score indicating more-severe disease activity. The remission rate (percentage of participants with remission) was calculated based on observed data (unadjusted remission rate) and also after applying a logistic regression model including the factors of treatment group, stratification factors (prior anti-TNF use and pre- versus post-Protocol Amendment 3) and baseline CDAI Score (adjusted remission rate). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Response at Week 12 | Baseline and week 12 | Response was defined as either remission (a CDAI score \< 150) or a decrease from baseline in the CDAI score of ≥ 100 points. The CDAI is a weighted, composite index of 8 disease variables (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extra-intestinal manifestations or fistula, use or non-use of antidiarrheal agents, presence or absence of an abdominal mass, hematocrit, and body weight). Scores range from approximately 0 to 600, with a higher score indicating more-severe disease activity. The response rate (percentage of participants with response) was calculated based on observed data (unadjusted response rate) and also after applying a logistic regression model including the factors of treatment group, stratification factors (prior anti-TNF use and pre- versus post-Protocol Amendment 3) and baseline CDAI score (adjusted response rate). |
| Percentage of Participants With Response at Week 8 | Baseline and week 8 | Response was defined as either remission (a CDAI score \< 150) or a decrease from baseline in the CDAI score of ≥ 100 points. The CDAI is a weighted, composite index of 8 disease variables (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extra-intestinal manifestations or fistula, use or non-use of antidiarrheal agents, presence or absence of an abdominal mass, hematocrit, and body weight). Scores range from approximately 0 to 600, with a higher score indicating more-severe disease activity. The response rate (percentage of participants with response) was calculated based on observed data (unadjusted response rate) and also after applying a logistic regression model including the factors of treatment group, stratification factors (prior anti-TNF use and pre- versus post-Protocol Amendment 3) and baseline CDAI score (adjusted response rate). |
| Percentage of Participants With Sustained Remission at Both Week 12 and Week 24 | Week 12 and week 24 | Remission was defined as a Crohn's Disease Activity Index (CDAI) score \< 150. Sustained remission was defined as achieving the criteria for remission at both week 12 and week 24. The CDAI is a weighted, composite index of 8 disease variables (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extra-intestinal manifestations or fistula, use or non-use of antidiarrheal agents, presence or absence of an abdominal mass, hematocrit, and body weight). Scores range from approximately 0 to 600, with a higher score indicating more-severe disease activity. The remission rate (percentage of participants with sustained remission) was calculated based on observed data (unadjusted remission rate) and also after applying a logistic regression model including the factors of treatment group, stratification factors (prior anti-TNF use and pre- versus post-Protocol Amendment 3) and baseline CDAI Score (adjusted remission rate). |
| Percentage of Participants With Remission at Week 12 | Week 12 | Remission was defined as a Crohn's Disease Activity Index (CDAI) score \< 150. The CDAI is a weighted, composite index of 8 disease variables (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extra-intestinal manifestations or fistula, use or non-use of antidiarrheal agents, presence or absence of an abdominal mass, hematocrit, and body weight). Scores range from approximately 0 to 600, with a higher score indicating more-severe disease activity. The remission rate (percentage of participants with remission) was calculated based on observed data (unadjusted remission rate) and also after applying a logistic regression model including the factors of treatment group, stratification factors (prior anti-TNF use and pre- versus post-Protocol Amendment 3) and baseline CDAI Score (adjusted remission rate). |
| Change From Baseline in CDAI Score at Week 12 | Baseline and week 12 | The CDAI is a weighted, composite index of 8 disease variables (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extra-intestinal manifestations or fistula, use or non-use of antidiarrheal agents, presence or absence of an abdominal mass, hematocrit, and body weight). Scores range from approximately 0 to 600, with a higher score indicating more-severe disease activity. |
| Change From Baseline in CDAI Score at Week 8 | Baseline and week 8 | The CDAI is a weighted, composite index of 8 disease variables (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extra-intestinal manifestations or fistula, use or non-use of antidiarrheal agents, presence or absence of an abdominal mass, hematocrit, and body weight). Scores range from approximately 0 to 600, with a higher score indicating more-severe disease activity. |
| Percentage of Participants With Sustained Remission at Both Week 8 and Week 24 | Week 8 and week 24 | Remission was defined as a Crohn's Disease Activity Index (CDAI) score \< 150. Sustained remission was defined as achieving the criteria for remission at both week 8 and week 24. The CDAI is a weighted, composite index of 8 disease variables (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extra-intestinal manifestations or fistula, use or non-use of antidiarrheal agents, presence or absence of an abdominal mass, hematocrit, and body weight). Scores range from approximately 0 to 600, with a higher score indicating more-severe disease activity. The remission rate (percentage of participants with sustained remission) was calculated based on observed data (unadjusted remission rate) and also after applying a logistic regression model including the factors of treatment group, stratification factors (prior anti-TNF use and pre- versus post-Protocol Amendment 3) and baseline CDAI Score (adjusted remission rate). |
Countries
Austria, Belgium, Canada, Czechia, Denmark, France, Germany, Hungary, Netherlands, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
This study was conducted at 84 centers in Canada, European Union, and the United States. Participants were enrolled from 04 December 2012 to 30 September 2014. The study consisted of a 24-week double-blind treatment period, a 108-week open-label treatment period, and a safety follow-up period.
Pre-assignment details
Participants were to be randomly assigned in a 2:1:2:1 ratio to 1 of 4 treatment groups. Due to a misalignment error, some participants were erroneously assigned to incorrect treatment resulting in a final randomization ratio different from that originally stipulated in the protocol.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants randomized to receive placebo by subcutaneous injection on day 1, week 2, week 4, and every 4 weeks thereafter until week 24 during the double-blind treatment period. | 100 |
| Abrilumab 21 mg Q4W Participants randomized to receive 21 mg abrilumab by subcutaneous injection on day 1, week 2, week 4, and every 4 weeks (Q4W) thereafter until week 24 during the double-blind treatment period. | 27 |
| Abrilumab 70 mg Q4W Participants randomized to receive 70 mg abrilumab by subcutaneous injection on day 1, week 2, week 4, and every 4 weeks thereafter until week 24 during the double-blind treatment period. | 85 |
| Abrilumab 210 mg Participants randomized to receive a single dose of 210 mg abrilumab by subcutaneous injection on day 1, followed by placebo at week 2, week 4, and every 4 weeks thereafter until week 24 during the double-blind treatment period. | 42 |
| Total | 254 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 1 | 0 |
| Overall Study | Decision by Sponsor | 3 | 1 | 2 | 2 |
| Overall Study | Lost to Follow-up | 9 | 1 | 4 | 1 |
| Overall Study | Withdrawal by Subject | 19 | 5 | 19 | 11 |
Baseline characteristics
| Characteristic | Placebo | Abrilumab 21 mg Q4W | Abrilumab 70 mg Q4W | Abrilumab 210 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 36.2 years STANDARD_DEVIATION 11.2 | 38.9 years STANDARD_DEVIATION 14.2 | 35.6 years STANDARD_DEVIATION 11.8 | 36.5 years STANDARD_DEVIATION 9.4 | 36.4 years STANDARD_DEVIATION 11.4 |
| Age, Customized 18 - 64 years | 99 Participants | 27 Participants | 85 Participants | 42 Participants | 253 Participants |
| Age, Customized ≥ 65 years | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Any Prior Anti-Tumor Necrosis Factor (TNF) Use No | 20 Participants | 6 Participants | 18 Participants | 9 Participants | 53 Participants |
| Any Prior Anti-Tumor Necrosis Factor (TNF) Use Yes | 80 Participants | 21 Participants | 67 Participants | 33 Participants | 201 Participants |
| Crohn's Disease Activity Index (CDAI) Score | 303.8 units on a scale STANDARD_DEVIATION 63.2 | 310.0 units on a scale STANDARD_DEVIATION 83.5 | 314.0 units on a scale STANDARD_DEVIATION 60.4 | 319.3 units on a scale STANDARD_DEVIATION 67.5 | 310.5 units on a scale STANDARD_DEVIATION 65.3 |
| Duration of Crohn's Diease | 11.07 years STANDARD_DEVIATION 8.33 | 12.58 years STANDARD_DEVIATION 9.55 | 10.69 years STANDARD_DEVIATION 7.75 | 11.31 years STANDARD_DEVIATION 7.54 | 11.15 years STANDARD_DEVIATION 8.12 |
| Enrollment Prior to Protocol Amendment 3 No | 56 Participants | 27 Participants | 56 Participants | 26 Participants | 165 Participants |
| Enrollment Prior to Protocol Amendment 3 Yes | 44 Participants | 0 Participants | 29 Participants | 16 Participants | 89 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 100 Participants | 26 Participants | 85 Participants | 41 Participants | 252 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 1 Participants | 3 Participants | 0 Participants | 5 Participants |
| Race/Ethnicity, Customized White | 97 Participants | 26 Participants | 82 Participants | 40 Participants | 245 Participants |
| Sex: Female, Male Female | 58 Participants | 12 Participants | 51 Participants | 23 Participants | 144 Participants |
| Sex: Female, Male Male | 42 Participants | 15 Participants | 34 Participants | 19 Participants | 110 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 |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 61 / 98 | 14 / 25 | 48 / 85 | 27 / 41 | 61 / 84 | 16 / 20 | 55 / 76 | 28 / 37 |
| serious Total, serious adverse events | 14 / 98 | 7 / 25 | 13 / 85 | 6 / 41 | 24 / 84 | 3 / 20 | 19 / 76 | 12 / 37 |
Outcome results
Primary
Percentage of Participants With Remission at Week 8
Remission was defined as a Crohn's Disease Activity Index (CDAI) score \< 150 at week 8. The CDAI is a weighted, composite index of 8 disease variables (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extra-intestinal manifestations or fistula, use or non-use of antidiarrheal agents, presence or absence of an abdominal mass, hematocrit, and body weight). Scores range from approximately 0 to 600, with a higher score indicating more-severe disease activity. The remission rate (percentage of participants with remission) was calculated based on observed data (unadjusted remission rate) and also after applying a logistic regression model including the factors of treatment group, stratification factors (prior anti-TNF use and pre- versus post-Protocol Amendment 3) and baseline CDAI Score (adjusted remission rate).
Time frame: Week 8
Population: The full analysis set includes all randomized participants who received at least 1 dose of study drug. Both unadjusted and adjusted remission rates were calculated using non-responder imputation, where participants with a missing CDAI Score at week 8 were counted as non-responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Remission at Week 8 | Adjusted remission rate | 12.8 percentage of participants |
| Placebo | Percentage of Participants With Remission at Week 8 | Unadjusted remission rate | 13.3 percentage of participants |
| Abrilumab 21 mg Q4W | Percentage of Participants With Remission at Week 8 | Adjusted remission rate | 23.1 percentage of participants |
| Abrilumab 21 mg Q4W | Percentage of Participants With Remission at Week 8 | Unadjusted remission rate | 23.1 percentage of participants |
| Abrilumab 70 mg Q4W | Percentage of Participants With Remission at Week 8 | Unadjusted remission rate | 14.3 percentage of participants |
| Abrilumab 70 mg Q4W | Percentage of Participants With Remission at Week 8 | Adjusted remission rate | 14.4 percentage of participants |
| Abrilumab 210 mg | Percentage of Participants With Remission at Week 8 | Unadjusted remission rate | 19.5 percentage of participants |
| Abrilumab 210 mg | Percentage of Participants With Remission at Week 8 | Adjusted remission rate | 21.9 percentage of participants |
Comparison: Comparisons between treatment groups were made using remission rates estimated from a logistic regression model adjusted for baseline CDAI score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).p-value: 0.7690% CI: [0.54, 2.44]Regression, Logistic
Comparison: The difference in remission rates, estimated from a logistic regression model adjusted for baseline CDAI score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).90% CI: [-7.9, 8.9]
Comparison: Comparisons between treatment groups were made using remission rates estimated from a logistic regression model adjusted for baseline CDAI score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).p-value: 0.2290% CI: [0.8, 4.57]Regression, Logistic
Comparison: The difference in remission rates, estimated from a logistic regression model adjusted for baseline CDAI score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).90% CI: [-4.6, 19.4]
Comparison: Comparisons between treatment groups were made using remission rates estimated from a logistic regression model adjusted for baseline CDAI score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).p-value: 0.2590% CI: [0.74, 5.73]Regression, Logistic
Comparison: The difference in remission rates, estimated from a logistic regression model adjusted for baseline CDAI score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).90% CI: [-6.8, 22.6]
Secondary
Change From Baseline in CDAI Score at Week 12
The CDAI is a weighted, composite index of 8 disease variables (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extra-intestinal manifestations or fistula, use or non-use of antidiarrheal agents, presence or absence of an abdominal mass, hematocrit, and body weight). Scores range from approximately 0 to 600, with a higher score indicating more-severe disease activity.
Time frame: Baseline and week 12
Population: The full analysis set includes all randomized participants who received at least 1 dose of study drug. Missing data were handled using the inverse probability weighting (IPW) method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in CDAI Score at Week 12 | -55.32 units on a scale | Standard Error 11.41 |
| Abrilumab 21 mg Q4W | Change From Baseline in CDAI Score at Week 12 | -92.16 units on a scale | Standard Error 21.85 |
| Abrilumab 70 mg Q4W | Change From Baseline in CDAI Score at Week 12 | -97.41 units on a scale | Standard Error 12.92 |
| Abrilumab 210 mg | Change From Baseline in CDAI Score at Week 12 | -96.11 units on a scale | Standard Error 22.78 |
Comparison: Comparisons between treatment arms was conducted using an inverse probability weighting (IPW) generalized estimating equations (GEE) model adjusted for prior anti-TNF use, pre-versus post-protocol amendment 3 and baseline CDAI score.p-value: 0.00690% CI: [-67.3, -16.9]IPW GEE Model
Comparison: Comparisons between treatment arms was conducted using an inverse probability weighting (IPW) generalized estimating equations (GEE) model adjusted for prior anti-TNF use, pre-versus post-protocol amendment 3 and baseline CDAI score.p-value: 0.09590% CI: [-81.5, -0.5]IPW GEE Model
Comparison: Comparisons between treatment arms was conducted using an inverse probability weighting (IPW) generalized estimating equations (GEE) model adjusted for prior anti-TNF use, pre-versus post-protocol amendment 3 and baseline CDAI score.p-value: 0.1190% CI: [-74.3, 0.7]IPW GEE Model
Secondary
Change From Baseline in CDAI Score at Week 8
The CDAI is a weighted, composite index of 8 disease variables (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extra-intestinal manifestations or fistula, use or non-use of antidiarrheal agents, presence or absence of an abdominal mass, hematocrit, and body weight). Scores range from approximately 0 to 600, with a higher score indicating more-severe disease activity.
Time frame: Baseline and week 8
Population: The full analysis set includes all randomized participants who received at least 1 dose of study drug. Missing data were handled using the inverse probability weighting (IPW) method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in CDAI Score at Week 8 | -64.05 units on a scale | Standard Error 9.62 |
| Abrilumab 21 mg Q4W | Change From Baseline in CDAI Score at Week 8 | -80.42 units on a scale | Standard Error 20.86 |
| Abrilumab 70 mg Q4W | Change From Baseline in CDAI Score at Week 8 | -91.52 units on a scale | Standard Error 11.78 |
| Abrilumab 210 mg | Change From Baseline in CDAI Score at Week 8 | -87.64 units on a scale | Standard Error 19.89 |
Comparison: Comparisons between treatment arms was conducted using an inverse probability weighting (IPW) generalized estimating equations (GEE) model adjusted for prior anti-TNF use, pre-versus post-protocol amendment 3 and baseline CDAI score.p-value: 0.04590% CI: [-50, -4.9]IPW GEE Model
Comparison: Comparisons between treatment arms was conducted using an inverse probability weighting (IPW) generalized estimating equations (GEE) model adjusted for prior anti-TNF use, pre-versus post-protocol amendment 3 and baseline CDAI score.p-value: 0.2790% CI: [-58.7, 11.5]IPW GEE Model
Comparison: Comparisons between treatment arms was conducted using an inverse probability weighting (IPW) generalized estimating equations (GEE) model adjusted for prior anti-TNF use, pre-versus post-protocol amendment 3 and baseline CDAI score.p-value: 0.4590% CI: [-51.8, 19.1]IPW GEE Model
Secondary
Percentage of Participants With Remission at Week 12
Remission was defined as a Crohn's Disease Activity Index (CDAI) score \< 150. The CDAI is a weighted, composite index of 8 disease variables (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extra-intestinal manifestations or fistula, use or non-use of antidiarrheal agents, presence or absence of an abdominal mass, hematocrit, and body weight). Scores range from approximately 0 to 600, with a higher score indicating more-severe disease activity. The remission rate (percentage of participants with remission) was calculated based on observed data (unadjusted remission rate) and also after applying a logistic regression model including the factors of treatment group, stratification factors (prior anti-TNF use and pre- versus post-Protocol Amendment 3) and baseline CDAI Score (adjusted remission rate).
Time frame: Week 12
Population: The full analysis set includes all randomized participants who received at least 1 dose of study drug. Both unadjusted and adjusted remission rates were calculated using non-responder imputation, where participants with a missing CDAI Score at week 12 were counted as non-responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Remission at Week 12 | Unadjusted remission rate | 18.1 percentage of participants |
| Placebo | Percentage of Participants With Remission at Week 12 | Adjusted remission rate | 20.1 percentage of participants |
| Abrilumab 21 mg Q4W | Percentage of Participants With Remission at Week 12 | Adjusted remission rate | 43.8 percentage of participants |
| Abrilumab 21 mg Q4W | Percentage of Participants With Remission at Week 12 | Unadjusted remission rate | 33.3 percentage of participants |
| Abrilumab 70 mg Q4W | Percentage of Participants With Remission at Week 12 | Unadjusted remission rate | 25.3 percentage of participants |
| Abrilumab 70 mg Q4W | Percentage of Participants With Remission at Week 12 | Adjusted remission rate | 31.0 percentage of participants |
| Abrilumab 210 mg | Percentage of Participants With Remission at Week 12 | Unadjusted remission rate | 27.0 percentage of participants |
| Abrilumab 210 mg | Percentage of Participants With Remission at Week 12 | Adjusted remission rate | 34.8 percentage of participants |
Comparison: Comparisons between treatment groups were made using remission rates estimated from a logistic regression model adjusted for baseline CDAI score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).p-value: 0.1690% CI: [0.9, 3.53]Regression, Logistic
Comparison: The difference in remission rates, estimated from a logistic regression model adjusted for baseline CDAI score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).90% CI: [-1.8, 21]
Comparison: Comparisons between treatment groups were made using remission rates estimated from a logistic regression model adjusted for baseline CDAI score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).p-value: 0.1390% CI: [0.93, 4.84]Regression, Logistic
Comparison: The difference in remission rates, estimated from a logistic regression model adjusted for baseline CDAI score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).90% CI: [-2.1, 27.5]
Comparison: Comparisons between treatment groups were made using remission rates estimated from a logistic regression model adjusted for baseline CDAI score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).p-value: 0.05690% CI: [1.17, 8.2]Regression, Logistic
Comparison: The difference in remission rates, estimated from a logistic regression model adjusted for baseline CDAI score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).90% CI: [2.8, 39.2]
Secondary
Percentage of Participants With Response at Week 12
Response was defined as either remission (a CDAI score \< 150) or a decrease from baseline in the CDAI score of ≥ 100 points. The CDAI is a weighted, composite index of 8 disease variables (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extra-intestinal manifestations or fistula, use or non-use of antidiarrheal agents, presence or absence of an abdominal mass, hematocrit, and body weight). Scores range from approximately 0 to 600, with a higher score indicating more-severe disease activity. The response rate (percentage of participants with response) was calculated based on observed data (unadjusted response rate) and also after applying a logistic regression model including the factors of treatment group, stratification factors (prior anti-TNF use and pre- versus post-Protocol Amendment 3) and baseline CDAI score (adjusted response rate).
Time frame: Baseline and week 12
Population: The full analysis set includes all randomized participants who received at least 1 dose of study drug. Both unadjusted and adjusted response rates were calculated using non-responder imputation, where participants with a missing CDAI Score at week 12 were counted as non-responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Response at Week 12 | Unadjusted response rate | 27.7 percentage of participants |
| Placebo | Percentage of Participants With Response at Week 12 | Adjusted response rate | 35.3 percentage of participants |
| Abrilumab 21 mg Q4W | Percentage of Participants With Response at Week 12 | Adjusted response rate | 50.4 percentage of participants |
| Abrilumab 21 mg Q4W | Percentage of Participants With Response at Week 12 | Unadjusted response rate | 41.7 percentage of participants |
| Abrilumab 70 mg Q4W | Percentage of Participants With Response at Week 12 | Adjusted response rate | 55.1 percentage of participants |
| Abrilumab 70 mg Q4W | Percentage of Participants With Response at Week 12 | Unadjusted response rate | 45.3 percentage of participants |
| Abrilumab 210 mg | Percentage of Participants With Response at Week 12 | Adjusted response rate | 50.9 percentage of participants |
| Abrilumab 210 mg | Percentage of Participants With Response at Week 12 | Unadjusted response rate | 43.2 percentage of participants |
Comparison: Comparisons between treatment groups were made using response rates estimated from a logistic regression model adjusted for baseline CDAI score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).p-value: 0.02190% CI: [1.27, 4.01]Regression, Logistic
Comparison: The difference in response rates, estimated from a logistic regression model adjusted for baseline CDAI score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).90% CI: [5.8, 31.3]
Comparison: Comparisons between treatment groups were made using response rates estimated from a logistic regression model adjusted for baseline CDAI score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).p-value: 0.1490% CI: [0.94, 3.87]Regression, Logistic
Comparison: The difference in response rates, estimated from a logistic regression model adjusted for baseline CDAI score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).90% CI: [-2.3, 29.7]
Comparison: Comparisons between treatment groups were made using response rates estimated from a logistic regression model adjusted for baseline CDAI score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).p-value: 0.2390% CI: [0.79, 4.39]Regression, Logistic
Comparison: The difference in response rates, estimated from a logistic regression model adjusted for baseline CDAI score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).90% CI: [-6.4, 31.3]
Secondary
Percentage of Participants With Response at Week 8
Response was defined as either remission (a CDAI score \< 150) or a decrease from baseline in the CDAI score of ≥ 100 points. The CDAI is a weighted, composite index of 8 disease variables (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extra-intestinal manifestations or fistula, use or non-use of antidiarrheal agents, presence or absence of an abdominal mass, hematocrit, and body weight). Scores range from approximately 0 to 600, with a higher score indicating more-severe disease activity. The response rate (percentage of participants with response) was calculated based on observed data (unadjusted response rate) and also after applying a logistic regression model including the factors of treatment group, stratification factors (prior anti-TNF use and pre- versus post-Protocol Amendment 3) and baseline CDAI score (adjusted response rate).
Time frame: Baseline and week 8
Population: The full analysis set includes all randomized participants who received at least 1 dose of study drug. Both unadjusted and adjusted response rates were calculated using non-responder imputation, where participants with a missing CDAI Score at week 8 were counted as non-responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Response at Week 8 | Adjusted response rate | 30.6 percentage of participants |
| Placebo | Percentage of Participants With Response at Week 8 | Unadjusted response rate | 26.4 percentage of participants |
| Abrilumab 21 mg Q4W | Percentage of Participants With Response at Week 8 | Unadjusted response rate | 33.3 percentage of participants |
| Abrilumab 21 mg Q4W | Percentage of Participants With Response at Week 8 | Adjusted response rate | 33.8 percentage of participants |
| Abrilumab 70 mg Q4W | Percentage of Participants With Response at Week 8 | Adjusted response rate | 46.6 percentage of participants |
| Abrilumab 70 mg Q4W | Percentage of Participants With Response at Week 8 | Unadjusted response rate | 42.9 percentage of participants |
| Abrilumab 210 mg | Percentage of Participants With Response at Week 8 | Adjusted response rate | 32.6 percentage of participants |
| Abrilumab 210 mg | Percentage of Participants With Response at Week 8 | Unadjusted response rate | 30.6 percentage of participants |
Comparison: Comparisons between treatment groups were made using response rates estimated from a logistic regression model adjusted for baseline CDAI score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).p-value: 0.04790% CI: [1.13, 3.47]Regression, Logistic
Comparison: The difference in response rates, estimated from a logistic regression model adjusted for baseline CDAI score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).90% CI: [2.4, 27.1]
Comparison: Comparisons between treatment groups were made using response rates estimated from a logistic regression model adjusted for baseline CDAI score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).p-value: 0.8490% CI: [0.52, 2.29]Regression, Logistic
Comparison: The difference in response rates, estimated from a logistic regression model adjusted for baseline CDAI score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).90% CI: [-15.2, 15.2]
Comparison: Comparisons between treatment groups were made using response rates estimated from a logistic regression model adjusted for baseline CDAI score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).p-value: 0.7890% CI: [0.49, 2.72]Regression, Logistic
Comparison: The difference in response rates, estimated from a logistic regression model adjusted for baseline CDAI score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).90% CI: [-17.4, 18.3]
Secondary
Percentage of Participants With Sustained Remission at Both Week 12 and Week 24
Remission was defined as a Crohn's Disease Activity Index (CDAI) score \< 150. Sustained remission was defined as achieving the criteria for remission at both week 12 and week 24. The CDAI is a weighted, composite index of 8 disease variables (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extra-intestinal manifestations or fistula, use or non-use of antidiarrheal agents, presence or absence of an abdominal mass, hematocrit, and body weight). Scores range from approximately 0 to 600, with a higher score indicating more-severe disease activity. The remission rate (percentage of participants with sustained remission) was calculated based on observed data (unadjusted remission rate) and also after applying a logistic regression model including the factors of treatment group, stratification factors (prior anti-TNF use and pre- versus post-Protocol Amendment 3) and baseline CDAI Score (adjusted remission rate).
Time frame: Week 12 and week 24
Population: The full analysis set includes all randomized participants who received at least 1 dose of study drug. Both unadjusted and adjusted sustained remission rates were calculated using non-responder imputation, where participants with missing CDAI scores at week 12 or week 24 were counted as non-responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Sustained Remission at Both Week 12 and Week 24 | Unadjusted remission rate | 8.2 percentage of participants |
| Placebo | Percentage of Participants With Sustained Remission at Both Week 12 and Week 24 | Adjusted remission rate | 9.0 percentage of participants |
| Abrilumab 21 mg Q4W | Percentage of Participants With Sustained Remission at Both Week 12 and Week 24 | Adjusted remission rate | 25.0 percentage of participants |
| Abrilumab 21 mg Q4W | Percentage of Participants With Sustained Remission at Both Week 12 and Week 24 | Unadjusted remission rate | 19.2 percentage of participants |
| Abrilumab 70 mg Q4W | Percentage of Participants With Sustained Remission at Both Week 12 and Week 24 | Unadjusted remission rate | 11.9 percentage of participants |
| Abrilumab 70 mg Q4W | Percentage of Participants With Sustained Remission at Both Week 12 and Week 24 | Adjusted remission rate | 14.0 percentage of participants |
| Abrilumab 210 mg | Percentage of Participants With Sustained Remission at Both Week 12 and Week 24 | Unadjusted remission rate | 17.1 percentage of participants |
| Abrilumab 210 mg | Percentage of Participants With Sustained Remission at Both Week 12 and Week 24 | Adjusted remission rate | 21.7 percentage of participants |
Comparison: Comparisons between treatment groups were made using sustained remission rates estimated from a logistic regression model adjusted for baseline CDAI score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).p-value: 0.3490% CI: [0.69, 3.91]Regression, Logistic
Comparison: The difference in sustained remission rates, estimated from a logistic regression model adjusted for baseline CDAI score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).90% CI: [-3.9, 11.7]
Comparison: Comparisons between treatment groups were made using sustained remission rates estimated from a logistic regression model adjusted for baseline CDAI score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).p-value: 0.07890% CI: [1.07, 7.41]Regression, Logistic
Comparison: The difference in sustained remission rates, estimated from a logistic regression model adjusted for baseline CDAI score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).90% CI: [-0.6, 22.6]
Comparison: Comparisons between treatment groups were made using sustained remission rates estimated from a logistic regression model adjusted for baseline CDAI score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).p-value: 0.08390% CI: [1.07, 10.66]Regression, Logistic
Comparison: The difference in sustained remission rates, estimated from a logistic regression model adjusted for baseline CDAI score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).90% CI: [-1.2, 28.3]
Secondary
Percentage of Participants With Sustained Remission at Both Week 8 and Week 24
Remission was defined as a Crohn's Disease Activity Index (CDAI) score \< 150. Sustained remission was defined as achieving the criteria for remission at both week 8 and week 24. The CDAI is a weighted, composite index of 8 disease variables (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extra-intestinal manifestations or fistula, use or non-use of antidiarrheal agents, presence or absence of an abdominal mass, hematocrit, and body weight). Scores range from approximately 0 to 600, with a higher score indicating more-severe disease activity. The remission rate (percentage of participants with sustained remission) was calculated based on observed data (unadjusted remission rate) and also after applying a logistic regression model including the factors of treatment group, stratification factors (prior anti-TNF use and pre- versus post-Protocol Amendment 3) and baseline CDAI Score (adjusted remission rate).
Time frame: Week 8 and week 24
Population: The full analysis set includes all randomized participants who received at least 1 dose of study drug. Both unadjusted and adjusted sustained remission rates were calculated using non-responder imputation, where participants with missing CDAI scores at week 8 or week 24 were counted as non-responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Sustained Remission at Both Week 8 and Week 24 | Unadjusted remission rate | 7.1 percentage of participants |
| Placebo | Percentage of Participants With Sustained Remission at Both Week 8 and Week 24 | Adjusted remission rate | 5.9 percentage of participants |
| Abrilumab 21 mg Q4W | Percentage of Participants With Sustained Remission at Both Week 8 and Week 24 | Adjusted remission rate | 14.3 percentage of participants |
| Abrilumab 21 mg Q4W | Percentage of Participants With Sustained Remission at Both Week 8 and Week 24 | Unadjusted remission rate | 15.4 percentage of participants |
| Abrilumab 70 mg Q4W | Percentage of Participants With Sustained Remission at Both Week 8 and Week 24 | Adjusted remission rate | 8.7 percentage of participants |
| Abrilumab 70 mg Q4W | Percentage of Participants With Sustained Remission at Both Week 8 and Week 24 | Unadjusted remission rate | 9.5 percentage of participants |
| Abrilumab 210 mg | Percentage of Participants With Sustained Remission at Both Week 8 and Week 24 | Unadjusted remission rate | 12.2 percentage of participants |
| Abrilumab 210 mg | Percentage of Participants With Sustained Remission at Both Week 8 and Week 24 | Adjusted remission rate | 12.7 percentage of participants |
Comparison: Comparisons between treatment groups were made using sustained remission rates estimated from a logistic regression model adjusted for baseline CDAI score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).p-value: 0.4790% CI: [0.59, 3.93]Regression, Logistic
Comparison: The difference in sustained remission rates, estimated from a logistic regression model adjusted for baseline CDAI score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).90% CI: [-4.7, 8.1]
Comparison: Comparisons between treatment groups were made using sustained remission rates estimated from a logistic regression model adjusted for baseline CDAI score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).p-value: 0.2190% CI: [0.77, 6.98]Regression, Logistic
Comparison: The difference in sustained remission rates, estimated from a logistic regression model adjusted for baseline CDAI score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).90% CI: [-4.3, 14.5]
Comparison: Comparisons between treatment groups were made using sustained remission rates estimated from a logistic regression model adjusted for baseline CDAI score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).p-value: 0.2190% CI: [0.75, 9.45]Regression, Logistic
Comparison: The difference in sustained remission rates, estimated from a logistic regression model adjusted for baseline CDAI score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).90% CI: [-6, 17.9]