Ulcerative Colitis
Conditions
Keywords
Ulcerative Colitis, IBD
Brief summary
The primary objective of this study is to evaluate the effect of abrilumab on induction of remission in adults with moderate to severe ulcerative colitis after 8 weeks of treatment as assessed by a total Mayo Score ≤ 2 points, with no individual subscore \> 1 point.
Detailed description
The study consisted of a 24-week double-blind, placebo-controlled treatment period followed by an open-label period of approximately 108 weeks. Participants were eligible to enter the open-label period of the study early if they did not achieve a response at week 8 and had an inadequate response at week 12 or later or if they experienced disease worsening after achieving response and/or remission at week 8. Failure to achieve response at week 8 was defined as failure to achieve a decrease from baseline in total Mayo Score ≥ 3 points and ≥ 30% decrease from baseline. Inadequate response at week 12 or later was defined as failure to achieve a 2-point decrease and 25% improvement in partial Mayo Score compared with screening and minimum partial Mayo Score ≥ 5 points. Disease worsening was defined as an increase in partial Mayo Score ≥ 3 points from the week 8 value and minimum partial Mayo Score ≥ 5 points with recto-sigmoidoscopy sub-score ≥ 2. Participants were planned to be randomized in a 2:1:2:2:2 ratio to placebo or abrilumab at 7 mg, 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 4:3:2. 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
BIOLOGICALAbrilumab
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
* Diagnosis of ulcerative colitis (UC) established ≥ 3 months before baseline by clinical and endoscopic evidence and corroborated by a histopathology report. * Moderate to severe active UC as defined by a total Mayo score of 6 to 12 with a centrally read rectosigmoidoscopy score ≥2 prior to baseline * Inadequate response to, loss of response to, or intolerance to at least one of the following treatments: * Immunomodulators * Anti-TNF agents * 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
Exclusion criteria
* Disease limited to the rectum (ie, within 10 cm of the anal verge) * Toxic megacolon * Crohn's Disease * History of subtotal colectomy with ileorectostomy or colectomy with ileoanal pouch, Koch pouch, or ileostomy for UC * Planned bowel surgery within 24 weeks from baseline * Stool positive for C. Difficile toxin at screening * History of gastrointestinal surgery within 8 weeks of baseline * Primary Sclerosing Cholangitis * Any uncontrolled or clinically significant systemic disease * Condition or disease that, in the opinion of the investigator would pose a risk to subject safety or interfere with study evaluation, procedures or completion. * Known to have tested positive for hepatitis B virus surface antigen, hepatitis C virus antibody or human immunodeficiency virus (HIV) * Underlying condition that predisposes subject to infections (eg, uncontrolled diabetes; history of splenectomy) * Known history of drug or alcohol abuse within 1 year of screening * Malignancy (other than resected cutaneous basal or cutaneous squamous cell carcinoma, or treated in situ cervical cancer considered cured) within 5 years of screening visit (if a malignancy occurred \> 5 years ago, subject is eligible with documentation of disease free state since treatment) * Immunosuppressive therapy with either cyclosporine A, tacrolimus, or mycophenolate mofetil, within 1 month prior to baseline * Prior exposure to anti tumor necrosis factor (TNF) agents, within 2 months, or 5 times the respective elimination half life (whichever is longer) prior to baseline * Any prior exposure to vedolizumab, rituximab, efalizumab, natalizumab * Use of topical (rectal) aminosalicylic acid (eg, mesalamine) or topical (rectal) steroids within 2 weeks prior to baseline * Use of intravenous or intramuscular corticosteroids within 2 weeks prior to screening and during screening * Previously treated with AMG 181 * Received any type of live attenuated vaccine \< 1 month prior to baseline or is planning to receive any such live attenuated vaccine over the course of the study * Treatment of infection with intravenous (within 30 days of baseline) or oral (within 14 days prior to baseline) antibiotics, antivirals, or antifungals * Abnormal laboratory results at screening * Any other laboratory abnormality, which, in the opinion of the investigator, will prevent the subject from completing the study or will interfere with the interpretation of the study results * Currently enrolled in another investigational device or drug study, or less than 30 days since ending another investigational device or drug study(s), or receiving other investigational agent(s)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Remission at Week 8 | Week 8 | Remission was defined as a total Mayo Score ≤ 2 points, with no individual subscore \> 1 point. The Mayo Score is a composite index of four items (stool frequency, rectal bleeding, rectosigmoidoscopy findings, and physician's global assessment) with each item graded semi-quantitatively on a score of 0 to 3 where 0 represents normal and higher score represents more severe disease status. The total Mayo Score is the sum of the four item scores, with a result ranging from 0 to 12 points. Higher scores represent more severe disease. 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 total Mayo Score (adjusted remission rate). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Response at Week 8 | Baseline and week 8 | Response was defined by a decrease from baseline in the total Mayo Score of ≥ 3 points and ≥ 30%, with an accompanying decrease in the rectal bleeding subscore ≥ 1 point or an absolute rectal bleeding subscore = 0 or 1. The Mayo Score is a composite index of four items (stool frequency, rectal bleeding, rectosigmoidoscopy findings, and physician's global assessment), each graded semi-quantitatively on a scale of 0 to 3 where 0 represents normal and higher score represents more severe disease status. The total Mayo Score is the sum of the four item scores, ranging from 0 to 12 points. Higher scores represent more severe disease. 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 total Mayo Score (adjusted response rate). |
| Percentage of Participants With Mucosal Healing at Week 8 | Week 8 | Mucosal healing was defined using the rectosigmoidoscopy subscore of Mayo assessment as absolute subscore for rectosigmoidoscopy of 0 or 1. Flexible rectosigmoidoscopy was performed as part of the Mayo assessment, graded semi-quantitatively on a scale of 0 to 3 where 0 represents normal and higher score represents more severe disease status. The healing rate (percentage of participants with mucosal healing) was calculated based on observed data (unadjusted healing 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 rectosigmoidoscopy score (adjusted healing rate). |
| Percentage of Participants With Sustained Remission at Week 8 and Week 24 | Week 8 and week 24 | Remission was defined as a total Mayo Score ≤ 2 points, with no individual subscore \> 1 point. Sustained remission was defined as achieving the criteria for remission at both week 8 and week 24. The Mayo Score is a composite index of four items (stool frequency, rectal bleeding, rectosigmoidoscopy findings, and physician's global assessment), each graded semi-quantitatively on a scale of 0 to 3 where 0 represents normal and higher scores represent more severe disease status. The total Mayo Score is the sum of the four item scores, with a and ranges from 0 to 12 points. Higher scores represent more severe disease. 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 total Mayo Score (adjusted remission rate). |
Countries
Australia, Austria, Belgium, Canada, Czechia, Denmark, Estonia, France, Germany, Greece, Hungary, Italy, Latvia, Netherlands, Norway, Poland, Russia, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled at 92 centers located in North America, Europe, and Australia from 16 November 2012 to 11 May 2015. 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 2:1:2:2:2 ratio to 1 of 5 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. | 117 |
| Abrilumab 7 mg Q4W Participants randomized to receive 7 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. | 22 |
| 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 thereafter until week 24 during the double-blind treatment period. | 40 |
| 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. | 100 |
| 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. | 80 |
| Total | 359 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Death | 1 | 0 | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 9 | 1 | 6 | 10 | 7 |
| Overall Study | Sponsor Decision | 3 | 0 | 0 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 20 | 6 | 7 | 25 | 18 |
Baseline characteristics
| Characteristic | Placebo | Abrilumab 7 mg Q4W | Abrilumab 21 mg Q4W | Abrilumab 70 mg Q4W | Abrilumab 210 mg | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 41.0 years STANDARD_DEVIATION 13.3 | 42.0 years STANDARD_DEVIATION 12.4 | 38.3 years STANDARD_DEVIATION 11.6 | 39.3 years STANDARD_DEVIATION 12.2 | 39.8 years STANDARD_DEVIATION 12 | 40.0 years STANDARD_DEVIATION 12.5 |
| Age, Customized 18 - 64 years | 113 Participants | 22 Participants | 40 Participants | 99 Participants | 80 Participants | 354 Participants |
| Age, Customized ≥ 65 years | 4 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 5 Participants |
| Any Prior Anti-Tumor Necrosis Factor (TNF) Use No | 48 Participants | 16 Participants | 30 Participants | 44 Participants | 41 Participants | 179 Participants |
| Any Prior Anti-Tumor Necrosis Factor (TNF) Use Yes | 69 Participants | 6 Participants | 10 Participants | 56 Participants | 39 Participants | 180 Participants |
| Duration of Ulcerative Colitis | 7.83 years STANDARD_DEVIATION 5.58 | 9.07 years STANDARD_DEVIATION 6.57 | 7.05 years STANDARD_DEVIATION 5.39 | 9.39 years STANDARD_DEVIATION 7.25 | 9.44 years STANDARD_DEVIATION 7.88 | 8.62 years STANDARD_DEVIATION 6.7 |
| Enrollment Prior to Protocol Amendment 3 No | 41 Participants | 22 Participants | 40 Participants | 42 Participants | 42 Participants | 187 Participants |
| Enrollment Prior to Protocol Amendment 3 Yes | 76 Participants | 0 Participants | 0 Participants | 58 Participants | 38 Participants | 172 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 0 Participants | 2 Participants | 0 Participants | 3 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 113 Participants | 22 Participants | 38 Participants | 100 Participants | 77 Participants | 350 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 5 Participants | 2 Participants | 1 Participants | 7 Participants | 1 Participants | 16 Participants |
| Race/Ethnicity, Customized Other | 3 Participants | 0 Participants | 0 Participants | 4 Participants | 1 Participants | 8 Participants |
| Race/Ethnicity, Customized White | 109 Participants | 20 Participants | 39 Participants | 89 Participants | 78 Participants | 335 Participants |
| Sex: Female, Male Female | 36 Participants | 8 Participants | 12 Participants | 32 Participants | 32 Participants | 120 Participants |
| Sex: Female, Male Male | 81 Participants | 14 Participants | 28 Participants | 68 Participants | 48 Participants | 239 Participants |
| Total Mayo Score | 8.9 units on a scale STANDARD_DEVIATION 1.5 | 8.1 units on a scale STANDARD_DEVIATION 1.4 | 8.6 units on a scale STANDARD_DEVIATION 1.7 | 9.0 units on a scale STANDARD_DEVIATION 1.5 | 9.1 units on a scale STANDARD_DEVIATION 1.4 | 8.9 units on a scale STANDARD_DEVIATION 1.5 |
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 | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 47 / 116 | 9 / 20 | 16 / 40 | 55 / 99 | 35 / 79 | 55 / 100 | 10 / 18 | 19 / 36 | 53 / 89 | 26 / 68 |
| serious Total, serious adverse events | 14 / 116 | 1 / 20 | 3 / 40 | 5 / 99 | 7 / 79 | 13 / 100 | 3 / 18 | 4 / 36 | 14 / 89 | 6 / 68 |
Outcome results
Primary
Percentage of Participants With Remission at Week 8
Remission was defined as a total Mayo Score ≤ 2 points, with no individual subscore \> 1 point. The Mayo Score is a composite index of four items (stool frequency, rectal bleeding, rectosigmoidoscopy findings, and physician's global assessment) with each item graded semi-quantitatively on a score of 0 to 3 where 0 represents normal and higher score represents more severe disease status. The total Mayo Score is the sum of the four item scores, with a result ranging from 0 to 12 points. Higher scores represent more severe disease. 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 total Mayo 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 Mayo Score at week 8 were counted as non-responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Remission at Week 8 | Unadjusted remission rate | 4.3 percentage of participants |
| Placebo | Percentage of Participants With Remission at Week 8 | Adjusted remission rate | 4.4 percentage of participants |
| Abrilumab 7 mg Q4W | Percentage of Participants With Remission at Week 8 | Unadjusted remission rate | 0.0 percentage of participants |
| Abrilumab 7 mg Q4W | Percentage of Participants With Remission at Week 8 | Adjusted remission rate | 1.6 percentage of participants |
| Abrilumab 21 mg Q4W | Percentage of Participants With Remission at Week 8 | Unadjusted remission rate | 2.5 percentage of participants |
| Abrilumab 21 mg Q4W | Percentage of Participants With Remission at Week 8 | Adjusted remission rate | 2.9 percentage of participants |
| Abrilumab 70 mg Q4W | Percentage of Participants With Remission at Week 8 | Adjusted remission rate | 13.5 percentage of participants |
| Abrilumab 70 mg Q4W | Percentage of Participants With Remission at Week 8 | Unadjusted remission rate | 13.3 percentage of participants |
| Abrilumab 210 mg | Percentage of Participants With Remission at Week 8 | Unadjusted remission rate | 12.7 percentage of participants |
| Abrilumab 210 mg | Percentage of Participants With Remission at Week 8 | Adjusted remission rate | 13.4 percentage of participants |
Comparison: Comparisons between treatment groups were made using remission rates estimated from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).p-value: 0.02190% CI: [1.41, 7.95]Regression, Logistic
Comparison: The difference in remission rates, estimated from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).90% CI: [1.6, 14.6]
Comparison: Comparisons between treatment groups were made using remission rates from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).p-value: 0.0390% CI: [1.34, 8.26]Regression, Logistic
Comparison: The difference in remission rates, estimated from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).90% CI: [0.8, 14.9]
Comparison: Comparisons between treatment groups were made using remission rates from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).p-value: 0.6490% CI: [0.13, 3.17]Regression, Logistic
Comparison: The difference in remission rates estimated from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).90% CI: [-5.2, 5.5]
Comparison: Comparisons between treatment groups were made using remission rates from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).p-value: 0.4990% CI: [0.03, 4.33]Regression, Logistic
Comparison: The difference in remission rates estimated from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).90% CI: [-5.5, 5.4]
Secondary
Percentage of Participants With Mucosal Healing at Week 8
Mucosal healing was defined using the rectosigmoidoscopy subscore of Mayo assessment as absolute subscore for rectosigmoidoscopy of 0 or 1. Flexible rectosigmoidoscopy was performed as part of the Mayo assessment, graded semi-quantitatively on a scale of 0 to 3 where 0 represents normal and higher score represents more severe disease status. The healing rate (percentage of participants with mucosal healing) was calculated based on observed data (unadjusted healing 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 rectosigmoidoscopy score (adjusted healing 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 healing rates were calculated using non-responder imputation, where participants with missing rectosigmoidoscopy scores at week 8 were counted as non-responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Mucosal Healing at Week 8 | Unadjusted healing rate | 21.6 percentage of participants |
| Placebo | Percentage of Participants With Mucosal Healing at Week 8 | Adjusted healing rate | 16.8 percentage of participants |
| Abrilumab 7 mg Q4W | Percentage of Participants With Mucosal Healing at Week 8 | Unadjusted healing rate | 14.3 percentage of participants |
| Abrilumab 7 mg Q4W | Percentage of Participants With Mucosal Healing at Week 8 | Adjusted healing rate | 12.2 percentage of participants |
| Abrilumab 21 mg Q4W | Percentage of Participants With Mucosal Healing at Week 8 | Unadjusted healing rate | 15.0 percentage of participants |
| Abrilumab 21 mg Q4W | Percentage of Participants With Mucosal Healing at Week 8 | Adjusted healing rate | 13.9 percentage of participants |
| Abrilumab 70 mg Q4W | Percentage of Participants With Mucosal Healing at Week 8 | Adjusted healing rate | 32.2 percentage of participants |
| Abrilumab 70 mg Q4W | Percentage of Participants With Mucosal Healing at Week 8 | Unadjusted healing rate | 32.7 percentage of participants |
| Abrilumab 210 mg | Percentage of Participants With Mucosal Healing at Week 8 | Unadjusted healing rate | 29.1 percentage of participants |
| Abrilumab 210 mg | Percentage of Participants With Mucosal Healing at Week 8 | Adjusted healing rate | 29.8 percentage of participants |
Comparison: Comparisons between treatment groups were made using healing rates estimated from a logistic regression model adjusted for baseline rectosigmoidoscopy score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).p-value: 0.01190% CI: [1.35, 4.07]Regression, Logistic
Comparison: The difference in adjusted healing rates, estimated from a logistic regression model adjusted for baseline rectosigmoidoscopy score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).90% CI: [4.8, 24]
Comparison: Comparisons between treatment groups were made using healing rates from a logistic regression model adjusted for baseline rectosigmoidoscopy score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).p-value: 0.04190% CI: [1.15, 3.82]Regression, Logistic
Comparison: The difference in adjusted healing rates, estimated from a logistic regression model adjusted for baseline rectosigmoidoscopy score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).90% CI: [1.7, 22.1]
Comparison: Comparisons between treatment groups were made using healing rates from a logistic regression model adjusted for baseline rectosigmoidoscopy score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).p-value: 0.6890% CI: [0.32, 1.97]Regression, Logistic
Comparison: The difference in adjusted healing rates, estimated from a logistic regression model adjusted for baseline rectosigmoidoscopy score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).90% CI: [-11.9, 9.4]
Comparison: Comparisons between treatment groups were made using healing rates from a logistic regression model adjusted for baseline rectosigmoidoscopy score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).p-value: 0.690% CI: [0.21, 2.22]Regression, Logistic
Comparison: The difference in adjusted healing rates, estimated from a logistic regression model adjusted for baseline rectosigmoidoscopy score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).90% CI: [-14.9, 11.3]
Secondary
Percentage of Participants With Response at Week 8
Response was defined by a decrease from baseline in the total Mayo Score of ≥ 3 points and ≥ 30%, with an accompanying decrease in the rectal bleeding subscore ≥ 1 point or an absolute rectal bleeding subscore = 0 or 1. The Mayo Score is a composite index of four items (stool frequency, rectal bleeding, rectosigmoidoscopy findings, and physician's global assessment), each graded semi-quantitatively on a scale of 0 to 3 where 0 represents normal and higher score represents more severe disease status. The total Mayo Score is the sum of the four item scores, ranging from 0 to 12 points. Higher scores represent more severe disease. 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 total Mayo 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 Mayo Score at week 8 were counted as non-responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Response at Week 8 | Unadjusted response rate | 25.9 percentage of participants |
| Placebo | Percentage of Participants With Response at Week 8 | Adjusted response rate | 26.0 percentage of participants |
| Abrilumab 7 mg Q4W | Percentage of Participants With Response at Week 8 | Unadjusted response rate | 14.3 percentage of participants |
| Abrilumab 7 mg Q4W | Percentage of Participants With Response at Week 8 | Adjusted response rate | 12.3 percentage of participants |
| Abrilumab 21 mg Q4W | Percentage of Participants With Response at Week 8 | Unadjusted response rate | 50.0 percentage of participants |
| Abrilumab 21 mg Q4W | Percentage of Participants With Response at Week 8 | Adjusted response rate | 47.2 percentage of participants |
| Abrilumab 70 mg Q4W | Percentage of Participants With Response at Week 8 | Adjusted response rate | 49.4 percentage of participants |
| Abrilumab 70 mg Q4W | Percentage of Participants With Response at Week 8 | Unadjusted response rate | 49.0 percentage of participants |
| Abrilumab 210 mg | Percentage of Participants With Response at Week 8 | Unadjusted response rate | 46.8 percentage of participants |
| Abrilumab 210 mg | Percentage of Participants With Response at Week 8 | Adjusted response rate | 47.4 percentage of participants |
Comparison: Comparisons between treatment groups were made using response rates estimated from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).p-value: <0.00190% CI: [1.71, 4.52]Regression, Logistic
Comparison: The difference in adjusted response rates, estimated from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).90% CI: [11.8, 33.2]
Comparison: Comparisons between treatment groups were made using response rates from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).p-value: 0.00390% CI: [1.53, 4.31]Regression, Logistic
Comparison: The difference in adjusted response rates, estimated from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).90% CI: [9, 31.8]
Comparison: Comparisons between treatment groups were made using response rates from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).p-value: 0.02490% CI: [1.29, 5.02]Regression, Logistic
Comparison: The difference in adjusted response rates, estimated from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).90% CI: [4.9, 34.1]
Comparison: Comparisons between treatment groups were made using response rates from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).p-value: 0.1890% CI: [0.13, 1.22]Regression, Logistic
Comparison: The difference in adjusted response rates, estimated from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).90% CI: [-24.4, 2.7]
Secondary
Percentage of Participants With Sustained Remission at Week 8 and Week 24
Remission was defined as a total Mayo Score ≤ 2 points, with no individual subscore \> 1 point. Sustained remission was defined as achieving the criteria for remission at both week 8 and week 24. The Mayo Score is a composite index of four items (stool frequency, rectal bleeding, rectosigmoidoscopy findings, and physician's global assessment), each graded semi-quantitatively on a scale of 0 to 3 where 0 represents normal and higher scores represent more severe disease status. The total Mayo Score is the sum of the four item scores, with a and ranges from 0 to 12 points. Higher scores represent more severe disease. 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 total Mayo 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 non-adjusted and adjusted remission rates were calculated using non-responder imputation, where participants with missing Mayo Score at week 8 or week 16 were counted as non-responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Sustained Remission at Week 8 and Week 24 | Unadjusted remission rate | 2.6 percentage of participants |
| Placebo | Percentage of Participants With Sustained Remission at Week 8 and Week 24 | Adjusted remission rate | 3.3 percentage of participants |
| Abrilumab 7 mg Q4W | Percentage of Participants With Sustained Remission at Week 8 and Week 24 | Adjusted remission rate | 1.6 percentage of participants |
| Abrilumab 7 mg Q4W | Percentage of Participants With Sustained Remission at Week 8 and Week 24 | Unadjusted remission rate | 0.0 percentage of participants |
| Abrilumab 21 mg Q4W | Percentage of Participants With Sustained Remission at Week 8 and Week 24 | Adjusted remission rate | 2.8 percentage of participants |
| Abrilumab 21 mg Q4W | Percentage of Participants With Sustained Remission at Week 8 and Week 24 | Unadjusted remission rate | 2.5 percentage of participants |
| Abrilumab 70 mg Q4W | Percentage of Participants With Sustained Remission at Week 8 and Week 24 | Unadjusted remission rate | 8.2 percentage of participants |
| Abrilumab 70 mg Q4W | Percentage of Participants With Sustained Remission at Week 8 and Week 24 | Adjusted remission rate | 9.1 percentage of participants |
| Abrilumab 210 mg | Percentage of Participants With Sustained Remission at Week 8 and Week 24 | Unadjusted remission rate | 3.8 percentage of participants |
| Abrilumab 210 mg | Percentage of Participants With Sustained Remission at Week 8 and Week 24 | Adjusted remission rate | 4.3 percentage of participants |
Comparison: Comparisons between treatment groups were made using sustained remission rates estimated from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).p-value: 0.0990% CI: [1.03, 8.36]Regression, Logistic
Comparison: The difference in adjusted sustained remission rates, estimated from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).90% CI: [-0.6, 10.4]
Comparison: Comparisons between treatment groups were made using sustained remission rates from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).p-value: 0.7290% CI: [0.38, 4.56]Regression, Logistic
Comparison: The difference in adjusted sustained remission rates, estimated from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).90% CI: [-4.7, 4.6]
Comparison: Comparisons between treatment groups were made using sustained remission rates from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).p-value: 0.8690% CI: [0.16, 4.41]Regression, Logistic
Comparison: The difference in adjusted sustained remission rates estimated from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).90% CI: [-3.9, 6.2]
Comparison: Comparisons between treatment groups were made using sustained remission rates from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).p-value: 0.6490% CI: [0.04, 6.31]Regression, Logistic
Comparison: The difference in adjusted sustained remission rates estimated from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).90% CI: [-4.2, 6.4]