Crohn's Disease (CD)
Conditions
Keywords
Crohn's Disease, Efficacy, Safety, Tolerability, ABT-494
Brief summary
This is a open-label extension (OLE) study designed to evaluate the long-term efficacy, safety, and tolerability of Upadacitinib (ABT-494).
Interventions
DRUGABT-494
Tablet: Oral
Sponsors
AbbVie
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Participant must have completed Study M13-740 through Week 52. * If female, participant must be postmenopausal, surgically sterile or on using a birth control method.
Exclusion criteria
* For any reason participant is considered by the investigator to be an unsuitable candidate * Female participant with a positive pregnancy test at Baseline or who is considering becoming pregnant during the study. * Participant is not in compliance with prior and concomitant medication requirements and procedures throughout Study M13-740.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Endoscopic Remission at Month 12 | Month 12 | Endoscopic remission was based on Simplified Endoscopic Score for Crohn's disease (SES-CD). The SES-CD assessed the size of mucosal ulcers, the ulcerated surface, the endoscopic extension and the presence of stenosis. SES-CD was based on endoscopic findings in 5 bowel segments (Ileum, right colon, transverse colon, left colon/sigmoid, and rectum). Each item was scored 0 to 3 per segment. The sum of the scores for each endoscopic variable ranged from 0 to 15, except for stenosis, where it varied between 0 and 11; total score ranged from 0 to 56. A lower score indicated better outcome. Endoscopic remission was defined as SES-CD ≤4 and at least two-point reduction versus Baseline of Study M13-740 and no subscore \>1 in any individual variable. |
| Percentage of Participants Achieving Clinical Remission at Month 12 | Month 12 | Clinical remission was defined as average daily stool frequency ≤1.5 and not worse than Baseline and average daily abdominal pain score ≤1.0 and not worse than baseline in Study M13-740. Abdominal pain was assessed using the CDAI component "abdominal pain" rated as none \[0\], mild \[1\], moderate \[2\], and severe \[3\]) (cumulative total over the past 7 days) as per the CDAI to calculate abdominal pain score; total score range from 0 to 105. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Endoscopic Remission | Week 0 (Baseline), Months 24, 36, 48, 60, 72, 84, and 96 | Endoscopic remission was based on SES-CD. The SES-CD assessed the size of mucosal ulcers, the ulcerated surface, the endoscopic extension and the presence of stenosis. SES-CD was based on endoscopic findings in 5 bowel segments (Ileum, right colon, transverse colon, left colon/sigmoid, and rectum). Each item was scored 0 to 3 per segment. The sum of the scores for each endoscopic variable ranged from 0 to 15, except for stenosis, where it varied between 0 and 11; total score ranged from 0 to 56. A lower score indicated better outcome. Endoscopic remission was defined as SES-CD ≤4 and at least two-point reduction versus Baseline of Study M13-740 and no subscore \>1 in any individual variable. Week 52 visit of Study M13-740 was considered Week 0 (Baseline) of Study M14-327. |
| Percentage of Participants Achieving Clinical Remission | Week 0 (Baseline), Months 12, 24, 36, 48, 60, 72, 84, and 96 | Clinical remission was defined as average daily stool frequency ≤1.5 and not worse than baseline and average daily abdominal pain score of ≤1.0 and not worse than baseline of Study M13-740. Abdominal pain was assessed using the CDAI component "abdominal pain" rated as none \[0\], mild \[1\], moderate \[2\], and severe \[3\]) (cumulative total over the past 7 days) and multiplied by a factor of 5 as per the CDAI to calculate abdominal pain score; total score range from 0 to 105. |
| Percentage of Participants Achieving Modified Clinical Remission | Week 0 (Baseline), Months 12, 24, 36, 48, 60, 72, 84, and 96 | Modified Clinical Remission was defined as average daily stool frequency ≤2.8 and not worse than baseline and average daily abdominal pain score of ≤1.0 and not worse than baseline of Study M13-740, among participants with stool frequency ≥4.0 or abdominal pain score ≥2.0 at Baseline of Study M13-740. Abdominal pain was assessed using the CDAI component "abdominal pain" rated as none \[0\], mild \[1\], moderate \[2\], and severe \[3\]) (cumulative total over the past 7 days) and multiplied by a factor of 5 as per the CDAI to calculate abdominal pain score; total score range from 0 to 105. |
| Percentage of Participants Achieving Remission | Week 0 (Baseline), Months 12, 24, 36, 48, 60, 72, 84, and 96 | Remission=clinical remission and endoscopic remission. Clinical remission was an average daily stool frequency ≤1.5 and not worse than baseline and average daily abdominal pain score of ≤1.0 and not worse than baseline of Study M13-740. Abdominal pain was assessed by CDAI component "abdominal pain"; rated as none \[0\], mild \[1\], moderate \[2\], severe \[3\]) cumulative total over the past 7 days and multiplied by a factor of 5 as per CDAI. Abdominal pain score range: 0 to 105. Endoscopic remission was based on SES-CD and assessed the size of mucosal ulcers, ulcerated surface, endoscopic extension and presence of stenosis. SES-CD was based on endoscopic findings in 5 bowel segments: Ileum, right colon, transverse colon, left colon/sigmoid, and rectum. Each item was scored 0 to 3 per segment. The sum of the scores for each endoscopic variable ranged from 0 to 15, except for stenosis, where it varied between 0 and 11; total score ranged from 0 to 56. A lower score indicated better outcome. |
| Percentage of Participants Achieving CDAI Remission | Week 0 (Baseline), Months 12, 24, 36, 48, 60, 72, 84, and 96 | CDAI is a measure of clinical response and remission that includes 8 variables encompassing both participant-reported (symptoms, general well-being) and objective (medication usage, laboratory variables, presence of abdominal mass or complications, and weight) variables. For symptoms scores, participants kept a diary card and the daily symptom scores were summed for the week. Each item in the CDAI was assigned a pre-specified factor to calculate the subtotals, and the subtotals of the items were totaled to produce the CDAI. Higher CDAI scores indicated greater disease activity, with a lower limit of 0 and no set upper limit. Total score range: 0 to 600. CDAI remission was defined as CDAI score \<150. |
| Percentage of Participants Achieving Inflammatory Bowel Disease Questionnaire (IBDQ) Remission | Week 0 (Baseline), Months 12, 24, 36, 48, 60, 72, 84, and 96 | The IBDQ is a 32-item (ranged 1 to 7) self-report questionnaire for participants with inflammatory bowel disease to evaluate the participant-reported outcomes across 4 dimensions: bowel symptoms (loose stools, abdominal pain), systemic symptoms (fatigue, altered sleep pattern), social function (work attendance, need to cancel social events), and emotional function (anger, depression, irritability). IBDQ total score range: 32 to 224. A higher score indicating better outcome. IBDQ remission was defined as IBDQ score ≥170. |
| Percentage of Participants Achieving Endoscopic Improvement | Week 0 (Baseline), Months 12, 24, 36, 48, 60, 72, 84, and 96 | Endoscopic improvement was defined as SES-CD at least 50% reduction from Baseline or endoscopic remission. Endoscopic remission was based on SES-CD and assessed the size of mucosal ulcers, ulcerated surface, endoscopic extension and presence of stenosis. SES-CD was based on endoscopic findings in 5 bowel segments: Ileum, right colon, transverse colon, left colon/sigmoid, and rectum. Each item was scored 0 to 3 per segment. The sum of the scores for each endoscopic variable ranged from 0 to 15, except for stenosis, where it varied between 0 and 11; total score ranged from 0 to 56. A lower score indicated better outcome. Endoscopic remission was defined as SES-CD ≤4 and at least 2-point reduction versus baseline of Study M13-740 and no subscore \>1 in any individual variable. Week 52 visit of Study M13-740 was considered Week 0 (Baseline) of Study M14-327. |
| Percentage of Participants Taking Steroids at Baseline (of Study M13-740) Who Are Steroid-Free at the Specified Timepoint in Study M14-327 | Months 12, 24, 36, 48, 60, 72, 84, and 96 | — |
| Percentage of Participants Achieving Remission and Normal C-Reactive Protein (CRP) | Week 0 (Baseline), Months 12, 24, 36, 48, 60, 72, 84, and 96 | Remission = clinical remission and endoscopic remission. Clinical remission was average daily stool frequency ≤1.5 and not worse than baseline and average daily abdominal pain score ≤1.0 and not worse than baseline of Study M13-740. Abdominal pain was assessed by CDAI component "abdominal pain" rated: none \[0\], mild \[1\], moderate \[2\], severe \[3\] cumulative total over the past 7 days and multiplied by a prespecified factor of 5; total score range from 0 to 105. Endoscopic remission was based on SES-CD and assessed size of mucosal ulcers, ulcerated surface, endoscopic extension and presence of stenosis. SES-CD was based on endoscopic findings in 5 bowel segments: Ileum, right colon, transverse colon, left colon/sigmoid, and rectum; scored 0 to 3 per segment. Sum of scores for each endoscopic variable ranged from 0 to 15, except for stenosis, where it varied between 0 and 11; total score ranged from 0 to 56. A lower score indicated better outcome. Normal CRP=high-sensitivity CRP \<5 mg/L. |
| Percentage of Participants in Remission at Week 0 Who Maintained Remission | Months 12, 24, 36, 48, 60, 72, 84, and 96 | Remission=clinical remission and endoscopic remission. Clinical remission was an average daily stool frequency ≤1.5 and not worse than baseline and average daily abdominal pain score of ≤1.0 and not worse than baseline of Study M13-740. Abdominal pain was assessed by CDAI component "abdominal pain"; rated as none \[0\], mild \[1\], moderate \[2\], severe \[3\]) cumulative total over the past 7 days and multiplied by a factor of 5 as per CDAI. Abdominal pain score range: 0 to 105. Endoscopic remission was based on SES-CD and assessed the size of mucosal ulcers, ulcerated surface, endoscopic extension and presence of stenosis. SES-CD was based on endoscopic findings in 5 bowel segments: Ileum, right colon, transverse colon, left colon/sigmoid, and rectum. Each item was scored 0 to 3 per segment. The sum of the scores for each endoscopic variable ranged from 0 to 15, except for stenosis, where it varied between 0 and 11; total score ranged from 0 to 56. A lower score indicated better outcome. |
| Percentage of Participants in Endoscopic Remission at Week 0 Who Maintained Endoscopic Remission | Months 12, 24, 36, 48, 60, 72, 84, and 96 | Endoscopic remission was based on SES-CD and assessed the size of mucosal ulcers, ulcerated surface, endoscopic extension and presence of stenosis. SES-CD was based on endoscopic findings in 5 bowel segments: Ileum, right colon, transverse colon, left colon/sigmoid, and rectum. Each item was scored 0 to 3 per segment. The sum of the scores for each endoscopic variable ranged from 0 to 15, except for stenosis, where it varied between 0 and 11; total score ranged from 0 to 56. A lower score indicated better outcome. Endoscopic remission was defined as SES-CD ≤4 and at least 2-point reduction versus baseline of Study M13-740 and no subscore \>1 in any individual variable. Week 52 visit of Study M13-740 was considered Week 0 (Baseline) of Study M14-327. |
| Percentage of Participants Achieving Response | Week 0 (Baseline), Months 12, 24, 36, 48, 60, 72, 84, and 96 | Response = clinical and endoscopic response. Clinical response was average daily stool frequency at least 30% reduction from baseline and average daily abdominal pain score not worse than baseline or average daily abdominal pain at least 30% reduction from baseline of Study M13-740 and average daily stool frequency not worse than baseline of Study M13-740. Abdominal pain based on CDAI component "abdominal pain" rated none \[0\], mild \[1\], moderate \[2\], severe \[3\] cumulative total over past 7 days and multiplied by prespecified factor of 5; total score range from 0-105. Endoscopic response was decrease ≥25% SES-CD from baseline of Study M13-740. SES-CD was based on endoscopic findings in 5 bowel segments (Ileum, right colon, transverse colon, left colon/sigmoid, rectum), scored 0 to 3 per each segment. Sum of the scores for each endoscopic variable ranged from 0-15, except for stenosis, where it varied between 0-11; total score ranged from 0-56. Lower score indicated better outcome. |
| Percentage of Participants Achieving Enhanced Clinical Response | Week 0 (Baseline), Months 12, 24, 36, 48, 60, 72, 84, and 96 | Enhanced Clinical Response was defined as average daily stool frequency at least 65% reduction from baseline and average daily abdominal pain score not worse than baseline or average daily abdominal pain score at least 35% reduction from baseline of Study M13-740 and average daily stool frequency not worse than baseline of Study M13-740.Abdominal pain was assessed by CDAI component "abdominal pain" rated none \[0\], mild \[1\], moderate \[2\], severe \[3\]; cumulative total over the past 7 days) and multiplied by prespecified factor of 5; total score range from 0 to 105. |
| Percentage of Participants Achieving Clinical Response | Week 0 (Baseline), Months 12, 24, 36, 48, 60, 72, 84, and 96 | Clinical response was defined as average daily stool frequency at least 30% reduction from Baseline and average daily abdominal pain score not worse than Baseline or average daily abdominal pain score at least 30% reduction from baseline of Study M13-740 and average daily stool frequency not worse than baseline of Study M13-740. Abdominal pain was assessed by CDAI component "abdominal pain" rated none \[0\], mild \[1\], moderate \[2\], severe \[3\]; cumulative total over the past 7 days) and multiplied by prespecified factor of 5; total score range from 0 to 105. |
| Percentage of Participants Achieving CDAI Response | Week 0 (Baseline), Months 12, 24, 36, 48, 60, 72, 84, and 96 | CDAI is a measure of clinical response and remission that includes 8 variables encompassing both participant-reported (symptoms, general well-being) and objective (medication usage, laboratory variables, presence of abdominal mass or complications, and weight) variables. For symptoms scores, participants kept a diary card and the daily symptom scores were summed for the week. Each item in the CDAI was assigned a prespecified factor to calculate the subtotals, and the subtotals of the items were totaled to produce the CDAI. Higher scores indicated greater disease activity, with a lower limit of 0 and no set upper limit. Total score range: 0 to 600. CDAI response was defined as a reduction in CDAI scores by ≥70 from baseline of Study M13-740. |
| Percentage of Participants Achieving Enhanced CDAI Response | Week 0 (Baseline), Months 12, 24, 36, 48, 60, 72, 84, and 96 | CDAI is a measure of clinical response and remission that includes 8 variables encompassing both participant-reported (symptoms, general well-being) and objective (medication usage, laboratory variables, presence of abdominal mass or complications, and weight) variables. For symptoms scores, participants kept a diary card and the daily symptom scores were summed for the week. Each item in the CDAI was assigned a prespecified factor to calculate the subtotals, and the subtotals of the items were totaled to produce the CDAI. Higher scores indicated greater disease activity, with a lower limit of 0 and no set upper limit. Total score range: 0 to 600. Enhanced CDAI response was defined as reduction in CDAI score by ≥100 from baseline of Study M13-740. |
| Percentage of Participants Achieving Endoscopic Response | Week 0 (Baseline), Months 12, 24, 36, 48, 60, 72, 84, and 96 | Endoscopic response was defined as decrease ≥ 25% SES-CD from Baseline of Study M13-740. SES-CD was based on endoscopic findings in 5 bowel segments (Ileum, right colon, transverse colon, left colon/sigmoid, and rectum). Each item was scored 0 to 3 per segment. The sum of the scores for each endoscopic variable ranged from 0 to 15, except for stenosis, where it varied between 0 and 11; total score ranged from 0 to 56. A lower score indicated better outcome. |
| Percentage of Participants Achieving IBDQ Response | Week 0 (Baseline), Months 12, 24, 36, 48, 60, 72, 84, and 96 | The IBDQ is a 32-item (ranged 1 to 7) self-report questionnaire for participants with inflammatory bowel disease to evaluate the participant-reported outcomes across 4 dimensions: bowel symptoms (loose stools, abdominal pain), systemic symptoms (fatigue, altered sleep pattern), social function (work attendance, need to cancel social events), and emotional function (anger, depression, irritability). IBDQ total Score range 32 to 224. A higher score indicated better outcome. IBDQ response was defined as an increase in IBDQ score ≥16 point from baseline of Study M13-740. |
| Percentage of Participants Taking Steroids at Baseline (of Study M13-740) Who Are Steroid-Free for At Least 90 Days and Achieve Remission | Months 12, 24, 36, 48, 60, 72, 84, and 96 | Remission = clinical remission and endoscopic remission. Clinical remission was average daily stool frequency ≤1.5, not worse than baseline, and average daily abdominal pain score ≤1.0 and not worse than baseline of Study M13-740. Abdominal pain was assessed using the CDAI component "abdominal pain" rated none \[0\], mild \[1\], moderate \[2\], severe \[3\] (cumulative total over the past 7 days) and multiplied by a factor of 5 as per the CDAI. Total score range 0 to 105. Endoscopic remission was defined as SES-CD ≤4 and at least 2- point reduction versus baseline of Study M13-740 and no subscore \>1 in any individual variable. SES-CD was based on endoscopic findings in 5 segments (Ileum, right colon, transverse colon, left colon/sigmoid, and rectum). Each item was scored 0 to 3 per segment. The sum of the scores for each endoscopic variable ranged from 0 to 15, except for stenosis, where it varied between 0 and 11; total score ranged from 0 to 56. A lower score indicated better outcome |
| Change From Baseline in Fecal Calprotectin Levels | Week 0 (Baseline), Months 12, 24, 36, 48, 60, 72, 84, and 96 | Stool samples were collected for analysis of fecal calprotectin levels. |
| Change From Baseline in Hs-CRP Levels | Week 0 (Baseline), Months 12, 24, 36, 48, 60, 72, 84, and 96 | — |
| Change From Baseline in IBDQ Total Score | Week 0 (Baseline), Months 12, 24, 36, 48, 60, 72, 84, and 96 | The IBDQ is a 32-item (ranged 1 to 7) self-report questionnaire for participants with inflammatory bowel disease to evaluate the participant-reported outcomes across 4 dimensions: bowel symptoms (loose stools, abdominal pain), systemic symptoms (fatigue, altered sleep pattern), social function (work attendance, need to cancel social events), and emotional function (anger, depression, irritability). IBDQ total score range from 32 to 224. A higher score indicated better outcome. |
| Change From Baseline in SES-CD | Week 0 (Baseline), Months 12, 24, 36, 48, 60, 72, 84, and 96 | The SES-CD assessed the size of mucosal ulcers, the ulcerated surface, the endoscopic extension and the presence of stenosis. SES-CD was based on endoscopic findings in 5 bowel segments (Ileum, right colon, transverse colon, left colon/sigmoid, and rectum). Each item was scored 0 to 3 per segment. The sum of the scores for each endoscopic variable ranged from 0 to 15, except for stenosis, where it varied between 0 and 11; total score ranged from 0 to 56. A lower score indicated better outcome. Endoscopic remission was defined as SES-CD ≤4 and at least two-point reduction versus Baseline of Study M13-740 and no subscore \>1 in any individual variable. |
Countries
Belgium, Canada, Czechia, Denmark, France, Germany, Hungary, Israel, Italy, Netherlands, New Zealand, Norway, Poland, Romania, Slovakia, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORABBVIE INC.
AbbVie
Participant flow
Pre-assignment details
Participants were evaluated for entry into Study M14-327 at the final study visit (Week 52) or up to 10 days following the Week 52 visit of Study M13-740 (NCT02365649). Participants who received the double-blind doses of upadacitinib during Study M13-740 were to receive open-label upadacitinib 15 milligrams (mg) once daily (QD). Participants who received the open-label doses (12 mg twice daily \[BID\] or 24 mg BID) during Study M13-740 were to receive open-label upadacitinib 30 mg QD.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 40.2 years STANDARD_DEVIATION 12.92 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 96 Participants |
| Sex: Female, Male Female | 56 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 31 | 0 / 29 | 1 / 47 |
| other Total, other adverse events | 31 / 31 | 27 / 29 | 41 / 47 |
| serious Total, serious adverse events | 9 / 31 | 7 / 29 | 15 / 47 |
Outcome results
None listed