Crohn's Disease
Conditions
Keywords
Crohn's Disease, ABBV-154
Brief summary
Crohn's disease (CD) is a long-lasting condition causing inflammation that can affect any part of the gut. CD may cause tiredness, loose stools with or without bleeding, abdominal pain, weight loss, and fever. This study evaluates how safe and effective ABBV-154 is in participants treated for moderately to severely active CD. Adverse events and change in the disease activity will be assessed. ABBV-154 is an investigational drug being evaluated for the treatment of CD. In the induction period, there is a 1 in 5 chance that participants will be assigned to placebo. Depending on the dose received in the induction period, there is a 1 in 2 or 1 in 3 chance that participants will be assigned to placebo in the maintenance period. Around 265 participants 18-75 years of age with moderately to severely active CD will be enrolled in the study at approximately 200 sites worldwide. The study is comprised of a 12-week double-blind, placebo-controlled induction period, followed by either a 12-week double-blind re-induction period for non-responders or a 40-week double-blind placebo-controlled maintenance period for responders. In the maintenance period, responders will be randomized to receive subcutaneous placebo or ABBV-154 in 2 different doses every other week. Participants in the placebo group who are initial responders will receive ABBV-154 in the maintenance period. There may be higher treatment burden for participants in this trial compared to their standard of care due to study procedures. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.
Interventions
DRUGABBV-154
Intravenous (IV) Infusion; Subcutaneous Injection
DRUGPlacebo
Intravenous (IV) infusion; Subcutaneous Injection
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of Crohn's Disease (CD) for at least 3 months prior to Baseline of the Induction Period. * Crohn's Disease Activity Index (CDAI) score 220 to 450 at Baseline of the Induction Period. * Endoscopic evidence of mucosal inflammation as documented by an Simple Endoscopic Score for Crohn's Disease (SES-CD) of \>= 6 for ileocolonic or colonic disease or SES-CD of \>= 4 for isolated ileal disease as scored by a central reader. All eligible scores must exclude the presence of narrowing component. * Demonstrated intolerance or inadequate response to one or more of the following biologic agents: infliximab, adalimumab, certolizumab pegol, vedolizumab, natalizumab, ustekinumab, or risankizumab.
Exclusion criteria
\- Participants with prior intolerance to adalimumab.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Endoscopic Response Per Simple Endoscopic Score for Crohn's Disease (SES-CD) | Baseline to Week 12 | The SES-CD assesses endoscopic disease severity by evidence of active intestinal mucosal inflammation. Endoscopic response is defined as a decrease in SES-CD \> 50% from Baseline (or for participants with isolated ileal disease and a Baseline SES-CD of 4, at least a 2-point reduction from Baseline). The SES-CD evaluates 4 endoscopic variables (ulcer size, ulcerated surface, affected surface, and narrowing, each on a scale from 0 (none) to 3 (worst) in 5 segments assessed during ileocolonoscopy (ileum, right colon, transverse colon, sigmoid and left colon, and rectum). The total score is the sum of the 4 endoscopic variable scores and ranges from 0 to 56, where higher scores indicate more severe disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Clinical Remission Per Crohn's Disease Activity Index (CDAI) | Induction Period Week 12 | The CDAI consists of 8 components; 6 are based on participant diary entries, participant interviews, and physical examinations, and 2 are based on laboratory analysis, and measurement of body weight and height. Clinical remission is defined as CDAI \< 150. |
| Percentage of Participants Achieving Clinical Remission Per Average Daily Liquid or Very Soft Stool Frequency (SF) and Average Daily Abdominal Pain (AP) Score (SF/AP) | Induction Period Week 12 | Clinical remission is defined as average daily liquid or very soft stool SF \<= 2.8 and not worse than Baseline and average daily AP score \<= 1 and not worse than Baseline. |
| Percentage of Participants Achieving Endoscopic Response Per SES-CD | Week 40 in the Maintenance Period | The SES-CD assesses endoscopic disease severity by evidence of active intestinal mucosal inflammation. Endoscopic response is defined as a decrease in SES-CD \> 50% from Baseline (or for participants with isolated ileal disease and a Baseline SES-CD of 4, at least a 2-point reduction from Baseline). |
| Percentage of Participants Achieving Clinical Remission Per CDAI | Week 40 in the Maintenance Period | The CDAI consists of 8 components; 6 are based on participant diary entries, participant interviews, and physical examinations, and 2 are based on laboratory analysis, and measurement of body weight and height. Clinical remission is defined as CDAI \< 150. |
| Percentage of Participants Achieving Clinical Remission Per SF/AP | Week 40 in the Maintenance Period | Clinical remission is defined as average daily liquid or very soft SF \<= 2.8 and not worse than Baseline and average daily AP score \<= 1 and not worse than Baseline. |
Countries
Australia, Austria, Belgium, Bulgaria, Canada, Czechia, France, Germany, Greece, Hungary, Israel, Italy, Japan, Netherlands, New Zealand, Poland, Portugal, Puerto Rico, Slovakia, South Korea, Spain, Taiwan, United Kingdom, United States
Participant flow
Pre-assignment details
In this Double-Blind study, subjects with Crohn's Disease (CD) were randomized into 5 groups for 12 weeks (Induction Period). At week 12, subjects were categorized as responders or non-responders. Responders were re-randomized into a 40-Week Maintenance Period. Non-responders were re-randomized into the 12-Week Re-Induction Period. At week 12 of the re-induction period, those achieving clinical/endoscopic response were re-randomized into the Maintenance Period.
Participants by arm
| Arm | Count |
|---|---|
| Double-Blind Induction Phase: Placebo Fixed dose placebo as described in the protocol.
Placebo: Intravenous (IV) infusion; Subcutaneous Injection. | 21 |
| Double-Blind Induction Phase: ABBV-154 150mg IV/ 80mg SC EOW ABBV-154:
150 mg Intravenous (IV) Infusion and Subcutaneous Injection 80 mg (SC) at end of week (EOW) 12-week double-blind Induction Phase. | 20 |
| Double-Blind Induction Phase: ABBV-154 300mg IV/ 230mg SC EOW ABBV-154:
300 mg Intravenous (IV) Infusion and Subcutaneous Injection 230 mg (SC) at end of week (EOW) 12-week double-blind Induction Phase. | 22 |
| Double-Blind Induction Phase: ABBV-154 600mg IV/ 530mg SC EOW ABBV-154:
600 mg Intravenous (IV) Infusion and Subcutaneous Injection 530 mg (SC) at end of week (EOW) 12-week double-blind Induction Phase. | 20 |
| Double-Blind Induction Phase: ABBV-154 600mg IV/ 530mg SC E4W ABBV-154:
600 mg Intravenous (IV) Infusion and Subcutaneous Injection 530 mg (SC) every 4 weeks (E4W) 12-week double-blind Induction Phase. | 23 |
| Total | 106 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Double-Blind Induction (12 Weeks) | Adverse Event | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 0 |
| Double-Blind Induction (12 Weeks) | Lack of Efficacy | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 |
| Double-Blind Induction (12 Weeks) | Study terminated by sponsor | 7 | 2 | 6 | 5 | 10 | 0 | 0 | 0 |
| Double-Blind Induction (12 Weeks) | Withdrawal by Subject | 2 | 3 | 0 | 0 | 0 | 0 | 0 | 0 |
| Double-Blind Maintenance (40 Weeks) | AE w/o receiving ABBV-154 rescue | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Double-Blind Maintenance (40 Weeks) | Lack of efficacy after receiving ABBV-154 rescue | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Double-Blind Maintenance (40 Weeks) | Lack of efficacy w/o receiving ABBV-154 rescue | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Double-Blind Maintenance (40 Weeks) | Other | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Double-Blind Maintenance (40 Weeks) | Study terminated by sponsor after ABBV-154 | 8 | 0 | 0 | 0 | 0 | 3 | 1 | 0 |
| Double-Blind Maintenance (40 Weeks) | Study terminated by sponsor w/o receiving ABBV-154 rescue | 6 | 0 | 0 | 0 | 0 | 10 | 11 | 3 |
| Double-Blind Maintenance (40 Weeks) | WD by subject w/o receiving ABBV-154 rescue | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Double-Blind Re-Induction (12 Weeks) | Adverse Event | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 |
| Double-Blind Re-Induction (12 Weeks) | Lack of Efficacy | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 |
| Double-Blind Re-Induction (12 Weeks) | Study terminated by sponsor | 0 | 0 | 1 | 4 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Double-Blind Induction Phase: ABBV-154 600mg IV/ 530mg SC EOW | Double-Blind Induction Phase: ABBV-154 600mg IV/ 530mg SC E4W | Total | Double-Blind Induction Phase: Placebo | Double-Blind Induction Phase: ABBV-154 150mg IV/ 80mg SC EOW | Double-Blind Induction Phase: ABBV-154 300mg IV/ 230mg SC EOW |
|---|---|---|---|---|---|---|
| Age, Continuous | 43.1 years STANDARD_DEVIATION 14.37 | 42.0 years STANDARD_DEVIATION 14.2 | 41.0 years STANDARD_DEVIATION 13.5 | 38.8 years STANDARD_DEVIATION 13.23 | 41.7 years STANDARD_DEVIATION 14.27 | 39.6 years STANDARD_DEVIATION 12.23 |
| Baseline Simple Endoscopic Score for Crohn's Disease (SES-CD) for ITT1 (all enrolled) | 16.13 SES-CD score (0-56) STANDARD_DEVIATION 6.472 | 14.65 SES-CD score (0-56) STANDARD_DEVIATION 6.748 | 15.19 SES-CD score (0-56) STANDARD_DEVIATION 8.011 | 14.86 SES-CD score (0-56) STANDARD_DEVIATION 8.928 | 13.53 SES-CD score (0-56) STANDARD_DEVIATION 6.816 | 16.73 SES-CD score (0-56) STANDARD_DEVIATION 10.533 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants | 23 Participants | 105 Participants | 21 Participants | 20 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 4 Participants | 22 Participants | 4 Participants | 5 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 14 Participants | 17 Participants | 80 Participants | 17 Participants | 15 Participants | 17 Participants |
| Sex: Female, Male Female | 9 Participants | 10 Participants | 43 Participants | 8 Participants | 8 Participants | 8 Participants |
| Sex: Female, Male Male | 11 Participants | 13 Participants | 63 Participants | 13 Participants | 12 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 20 | 0 / 22 | 0 / 20 | 0 / 23 | 0 / 4 | 0 / 4 | 0 / 8 | 0 / 8 | 0 / 18 | 0 / 14 | 0 / 13 | 0 / 4 | 0 / 14 |
| other Total, other adverse events | 7 / 21 | 12 / 20 | 11 / 22 | 14 / 20 | 13 / 23 | 4 / 4 | 1 / 4 | 5 / 8 | 4 / 8 | 9 / 18 | 10 / 14 | 8 / 13 | 2 / 4 | 8 / 14 |
| serious Total, serious adverse events | 3 / 21 | 3 / 20 | 2 / 22 | 0 / 20 | 3 / 23 | 0 / 4 | 0 / 4 | 1 / 8 | 2 / 8 | 3 / 18 | 1 / 14 | 0 / 13 | 0 / 4 | 1 / 14 |
Outcome results
Primary
Percentage of Participants Achieving Endoscopic Response Per Simple Endoscopic Score for Crohn's Disease (SES-CD)
The SES-CD assesses endoscopic disease severity by evidence of active intestinal mucosal inflammation. Endoscopic response is defined as a decrease in SES-CD \> 50% from Baseline (or for participants with isolated ileal disease and a Baseline SES-CD of 4, at least a 2-point reduction from Baseline). The SES-CD evaluates 4 endoscopic variables (ulcer size, ulcerated surface, affected surface, and narrowing, each on a scale from 0 (none) to 3 (worst) in 5 segments assessed during ileocolonoscopy (ileum, right colon, transverse colon, sigmoid and left colon, and rectum). The total score is the sum of the 4 endoscopic variable scores and ranges from 0 to 56, where higher scores indicate more severe disease.
Time frame: Baseline to Week 12
Population: ITT1 Population for whom data was collected and available for analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Percentage of Participants Achieving Endoscopic Response Per Simple Endoscopic Score for Crohn's Disease (SES-CD) | 0 Participants |
| ABBV-154 150mg IV, 80mg SC EOW | Percentage of Participants Achieving Endoscopic Response Per Simple Endoscopic Score for Crohn's Disease (SES-CD) | 1 Participants |
| ABBV-154 300mg IV, 230mg SC EOW | Percentage of Participants Achieving Endoscopic Response Per Simple Endoscopic Score for Crohn's Disease (SES-CD) | 4 Participants |
| ABBV-154 600mg IV, 530mg SC EOW | Percentage of Participants Achieving Endoscopic Response Per Simple Endoscopic Score for Crohn's Disease (SES-CD) | 4 Participants |
| ABBV-154 600mg IV, 530mg SC E4W | Percentage of Participants Achieving Endoscopic Response Per Simple Endoscopic Score for Crohn's Disease (SES-CD) | 3 Participants |
95% CI: [-6.3, 20.6]
95% CI: [6.7, 60]
95% CI: [4.9, 52.2]
95% CI: [1, 53.6]
Secondary
Percentage of Participants Achieving Clinical Remission Per Average Daily Liquid or Very Soft Stool Frequency (SF) and Average Daily Abdominal Pain (AP) Score (SF/AP)
Clinical remission is defined as average daily liquid or very soft stool SF \<= 2.8 and not worse than Baseline and average daily AP score \<= 1 and not worse than Baseline.
Time frame: Induction Period Week 12
Population: ITT1 Population for whom data was collected and available for analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Percentage of Participants Achieving Clinical Remission Per Average Daily Liquid or Very Soft Stool Frequency (SF) and Average Daily Abdominal Pain (AP) Score (SF/AP) | 2 Participants |
| ABBV-154 150mg IV, 80mg SC EOW | Percentage of Participants Achieving Clinical Remission Per Average Daily Liquid or Very Soft Stool Frequency (SF) and Average Daily Abdominal Pain (AP) Score (SF/AP) | 4 Participants |
| ABBV-154 300mg IV, 230mg SC EOW | Percentage of Participants Achieving Clinical Remission Per Average Daily Liquid or Very Soft Stool Frequency (SF) and Average Daily Abdominal Pain (AP) Score (SF/AP) | 7 Participants |
| ABBV-154 600mg IV, 530mg SC EOW | Percentage of Participants Achieving Clinical Remission Per Average Daily Liquid or Very Soft Stool Frequency (SF) and Average Daily Abdominal Pain (AP) Score (SF/AP) | 6 Participants |
| ABBV-154 600mg IV, 530mg SC E4W | Percentage of Participants Achieving Clinical Remission Per Average Daily Liquid or Very Soft Stool Frequency (SF) and Average Daily Abdominal Pain (AP) Score (SF/AP) | 6 Participants |
95% CI: [3.8, 74.5]
95% CI: [-18.5, 41]
95% CI: [5, 71.9]
95% CI: [-7, 56.2]
Secondary
Percentage of Participants Achieving Clinical Remission Per CDAI
The CDAI consists of 8 components; 6 are based on participant diary entries, participant interviews, and physical examinations, and 2 are based on laboratory analysis, and measurement of body weight and height. Clinical remission is defined as CDAI \< 150.
Time frame: Week 40 in the Maintenance Period
Population: Data were not collected for this outcome due to early termination of the study.
Secondary
Percentage of Participants Achieving Clinical Remission Per Crohn's Disease Activity Index (CDAI)
The CDAI consists of 8 components; 6 are based on participant diary entries, participant interviews, and physical examinations, and 2 are based on laboratory analysis, and measurement of body weight and height. Clinical remission is defined as CDAI \< 150.
Time frame: Induction Period Week 12
Population: ITT1 Population for whom data was collected and available for analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Percentage of Participants Achieving Clinical Remission Per Crohn's Disease Activity Index (CDAI) | 2 Participants |
| ABBV-154 150mg IV, 80mg SC EOW | Percentage of Participants Achieving Clinical Remission Per Crohn's Disease Activity Index (CDAI) | 4 Participants |
| ABBV-154 300mg IV, 230mg SC EOW | Percentage of Participants Achieving Clinical Remission Per Crohn's Disease Activity Index (CDAI) | 6 Participants |
| ABBV-154 600mg IV, 530mg SC EOW | Percentage of Participants Achieving Clinical Remission Per Crohn's Disease Activity Index (CDAI) | 5 Participants |
| ABBV-154 600mg IV, 530mg SC E4W | Percentage of Participants Achieving Clinical Remission Per Crohn's Disease Activity Index (CDAI) | 4 Participants |
95% CI: [-19.8, 43.6]
95% CI: [-4.8, 63.8]
95% CI: [-13.7, 51.8]
95% CI: [-13.6, 60.3]
Secondary
Percentage of Participants Achieving Clinical Remission Per SF/AP
Clinical remission is defined as average daily liquid or very soft SF \<= 2.8 and not worse than Baseline and average daily AP score \<= 1 and not worse than Baseline.
Time frame: Week 40 in the Maintenance Period
Population: Data were not collected for this outcome due to early termination of the study.
Secondary
Percentage of Participants Achieving Endoscopic Response Per SES-CD
The SES-CD assesses endoscopic disease severity by evidence of active intestinal mucosal inflammation. Endoscopic response is defined as a decrease in SES-CD \> 50% from Baseline (or for participants with isolated ileal disease and a Baseline SES-CD of 4, at least a 2-point reduction from Baseline).
Time frame: Week 40 in the Maintenance Period
Population: Data were not collected for this outcome due to early termination of the study.