Trial Outcomes & Findings for A Study to Test Whether BI 706321 Combined With Ustekinumab Helps People With Crohn's Disease (NCT NCT04978493)
NCT ID: NCT04978493
Last Updated: 2025-09-04
Results Overview
Absolute change from baseline in Simple Endoscopic Score for Crohn's disease (SES-CD) at Week 12 is reported. The SES-CD is a numerical grading system composed of 4 variables (presence of ulcers, ulcerated surface, affected surface, presence of narrowings) recorded sequentially in 5 segments: rectum, left colon, transverse colon, right colon, ileum. Each variable is assigned a value from 0 to 3, and the total score, ranging from 0 to 56, is obtained by adding each variable. Higher values indicate worse endoscopic inflammation. To achieve a score of 56, the maximum score for the "presence of narrowings" variable has to be be 2 (not 3) for the four segments leading up to the ileum. The analysis was a restricted maximum likelihood (REML) based analysis of covariance (ANCOVA). For the ANCOVA model, absolute change in SES-CD score was the dependent variable, treatment group and baseline corticosteroid use (yes/no) were fixed effects and baseline SES-CD score was a continuous covariate.
TERMINATED
PHASE2
49 participants
Within 28 days before randomization (baseline) and 12 weeks after first drug administration.
2025-09-04
Participant Flow
This was a Phase IIa, randomised, double-blind, placebo-controlled evaluation of male and female patients with Crohn's Disease (CD), using BI 706321 therapy in combination with a backbone ustekinumab induction regimen.
Subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) met all inclusion and no exclusion criteria. Subjects were not to be allocated to a treatment group if any entry criteria were violated. Subjects signed and dated an informed consent form according to local regulatory and legal requirements, and were informed that they were free to withdraw their consent at any time without penalty or prejudice.
Participant milestones
| Measure |
BI 706321 and Ustekinumab
Participants with moderately to severely active Crohn's Disease (CD) administered one dose of 8 milligram (mg) BI 706321 as tablets orally once per day in the morning for 12 weeks in conjunction with standard induction dosing of ustekinumab, followed by ustekinumab maintenance dosing for an additional 36 weeks.
A single intravenous infusion of 260 mg ustekinumab (body weight ≤55 kilogram \[kg\]), 390 mg ustekinumab (body weight 55-85 kg), or 520 mg ustekinumab (body weight \>85 kg) was administered on Day 0, followed by subcutaneous injection of 90 mg ustekinumab every 8 weeks.
|
Placebo and Ustekinumab
Participants with moderately to severely active CD administered one dose of placebo matching BI 706321 as tablets orally once per day in the morning for 12 weeks in conjunction with standard induction dosing of ustekinumab, followed by ustekinumab maintenance dosing for an additional 36 weeks.
A single intravenous infusion of 260 mg ustekinumab (body weight ≤55 kilogram \[kg\]), 390 mg ustekinumab (body weight 55-85 kg), or 520 mg ustekinumab (body weight \>85 kg) was administered on Day 0, followed by subcutaneous injection of 90 mg ustekinumab every 8 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
24
|
25
|
|
Overall Study
COMPLETED
|
23
|
24
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
Reasons for withdrawal
| Measure |
BI 706321 and Ustekinumab
Participants with moderately to severely active Crohn's Disease (CD) administered one dose of 8 milligram (mg) BI 706321 as tablets orally once per day in the morning for 12 weeks in conjunction with standard induction dosing of ustekinumab, followed by ustekinumab maintenance dosing for an additional 36 weeks.
A single intravenous infusion of 260 mg ustekinumab (body weight ≤55 kilogram \[kg\]), 390 mg ustekinumab (body weight 55-85 kg), or 520 mg ustekinumab (body weight \>85 kg) was administered on Day 0, followed by subcutaneous injection of 90 mg ustekinumab every 8 weeks.
|
Placebo and Ustekinumab
Participants with moderately to severely active CD administered one dose of placebo matching BI 706321 as tablets orally once per day in the morning for 12 weeks in conjunction with standard induction dosing of ustekinumab, followed by ustekinumab maintenance dosing for an additional 36 weeks.
A single intravenous infusion of 260 mg ustekinumab (body weight ≤55 kilogram \[kg\]), 390 mg ustekinumab (body weight 55-85 kg), or 520 mg ustekinumab (body weight \>85 kg) was administered on Day 0, followed by subcutaneous injection of 90 mg ustekinumab every 8 weeks.
|
|---|---|---|
|
Overall Study
No reason available
|
0
|
1
|
|
Overall Study
Adverse Event
|
1
|
0
|
Baseline Characteristics
A Study to Test Whether BI 706321 Combined With Ustekinumab Helps People With Crohn's Disease
Baseline characteristics by cohort
| Measure |
BI 706321 and Ustekinumab
n=24 Participants
Participants with moderately to severely active Crohn's Disease (CD) administered one dose of 8 milligram (mg) BI 706321 as tablets orally once per day in the morning for 12 weeks in conjunction with standard induction dosing of ustekinumab, followed by ustekinumab maintenance dosing for an additional 36 weeks.
A single intravenous infusion of 260 mg ustekinumab (body weight ≤55 kilogram \[kg\]), 390 mg ustekinumab (body weight 55-85 kg), or 520 mg ustekinumab (body weight \>85 kg) was administered on Day 0, followed by subcutaneous injection of 90 mg ustekinumab every 8 weeks.
|
Placebo and Ustekinumab
n=25 Participants
Participants with moderately to severely active CD administered one dose of placebo matching BI 706321 as tablets orally once per day in the morning for 12 weeks in conjunction with standard induction dosing of ustekinumab, followed by ustekinumab maintenance dosing for an additional 36 weeks.
A single intravenous infusion of 260 mg ustekinumab (body weight ≤55 kilogram \[kg\]), 390 mg ustekinumab (body weight 55-85 kg), or 520 mg ustekinumab (body weight \>85 kg) was administered on Day 0, followed by subcutaneous injection of 90 mg ustekinumab every 8 weeks.
|
Total
n=49 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
38.8 Years
STANDARD_DEVIATION 14.9 • n=5 Participants
|
47.8 Years
STANDARD_DEVIATION 13.8 • n=7 Participants
|
43.4 Years
STANDARD_DEVIATION 14.9 • n=5 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
21 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
46 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
22 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
44 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Simple Endoscopic Score for Crohn's disease (SES-CD)
|
14.1 Score on a scale
STANDARD_DEVIATION 5.8 • n=5 Participants
|
12.0 Score on a scale
STANDARD_DEVIATION 4.9 • n=7 Participants
|
13.0 Score on a scale
STANDARD_DEVIATION 5.4 • n=5 Participants
|
PRIMARY outcome
Timeframe: Within 28 days before randomization (baseline) and 12 weeks after first drug administration.Population: Full analysis set (FAS): all randomized patients who received at least 1 dose of trial medication and have analyzable post-baseline data (observed or imputed) in at least 1 efficacy/biological/histological parameter. If a subject discontinued after 6 weeks and had an assessment during the Week 8 visit window, the change in SES-CD score at Week 8 was carried forward to the Week 12 time point and used. If there was no post-baseline endoscopic assessment, baseline value was carried forward.
Absolute change from baseline in Simple Endoscopic Score for Crohn's disease (SES-CD) at Week 12 is reported. The SES-CD is a numerical grading system composed of 4 variables (presence of ulcers, ulcerated surface, affected surface, presence of narrowings) recorded sequentially in 5 segments: rectum, left colon, transverse colon, right colon, ileum. Each variable is assigned a value from 0 to 3, and the total score, ranging from 0 to 56, is obtained by adding each variable. Higher values indicate worse endoscopic inflammation. To achieve a score of 56, the maximum score for the "presence of narrowings" variable has to be be 2 (not 3) for the four segments leading up to the ileum. The analysis was a restricted maximum likelihood (REML) based analysis of covariance (ANCOVA). For the ANCOVA model, absolute change in SES-CD score was the dependent variable, treatment group and baseline corticosteroid use (yes/no) were fixed effects and baseline SES-CD score was a continuous covariate.
Outcome measures
| Measure |
BI 706321 and Ustekinumab
n=24 Participants
Participants with moderately to severely active Crohn's Disease (CD) administered one dose of 8 milligram (mg) BI 706321 as tablets orally once per day in the morning for 12 weeks in conjunction with standard induction dosing of ustekinumab, followed by ustekinumab maintenance dosing for an additional 36 weeks.
A single intravenous infusion of 260 mg ustekinumab (body weight ≤55 kilogram \[kg\]), 390 mg ustekinumab (body weight 55-85 kg), or 520 mg ustekinumab (body weight \>85 kg) was administered on Day 0, followed by subcutaneous injection of 90 mg ustekinumab every 8 weeks.
|
Placebo and Ustekinumab
n=25 Participants
Participants with moderately to severely active CD administered one dose of placebo matching BI 706321 as tablets orally once per day in the morning for 12 weeks in conjunction with standard induction dosing of ustekinumab, followed by ustekinumab maintenance dosing for an additional 36 weeks.
A single intravenous infusion of 260 mg ustekinumab (body weight ≤55 kilogram \[kg\]), 390 mg ustekinumab (body weight 55-85 kg), or 520 mg ustekinumab (body weight \>85 kg) was administered on Day 0, followed by subcutaneous injection of 90 mg ustekinumab every 8 weeks.
|
|---|---|---|
|
Absolute Change From Baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD) at Week 12
|
-1.69 Score on a scale
Interval -3.75 to 0.37
|
-3.62 Score on a scale
Interval -5.63 to -1.6
|
SECONDARY outcome
Timeframe: Within 28 days before randomization (baseline) and 12 weeks after first drug administration.Population: Full analysis set (FAS): all randomized patients who received at least 1 dose of trial medication and have analyzable post-baseline data (observed or imputed) in at least 1 efficacy/biological/histological parameter. If a subject discontinued after 6 weeks and had an assessment during the Week 8 visit window, the change in SES-CD score at Week 8 was carried forward to the Week 12 time point and used. If there was no post-baseline endoscopic assessment, baseline value was carried forward.
Percent change in Simple Endoscopic Score for Crohn's disease (SES-CD) from baseline at Week 12 is reported. The SES-CD is a numerical grading system composed of 4 variables (presence of ulcers, ulcerated surface, affected surface, presence of narrowings) recorded sequentially in 5 segments: rectum, left colon, transverse colon, right colon, ileum. Each variable is assigned a value from 0 to 3, and the total score, ranging from 0 to 56, is obtained by adding each variable. Higher values indicate worse endoscopic inflammation. To achieve a score of 56, the maximum score for the "presence of narrowings" variable has to be be 2 (not 3) for the four segments leading up to the ileum. The analysis was a restricted maximum likelihood (REML) based analysis of covariance (ANCOVA). For the ANCOVA model, absolute change in SES-CD score was the dependent variable, treatment group and baseline corticosteroid use (yes/no) were fixed effects and baseline SES-CD score was a continuous covariate.
Outcome measures
| Measure |
BI 706321 and Ustekinumab
n=24 Participants
Participants with moderately to severely active Crohn's Disease (CD) administered one dose of 8 milligram (mg) BI 706321 as tablets orally once per day in the morning for 12 weeks in conjunction with standard induction dosing of ustekinumab, followed by ustekinumab maintenance dosing for an additional 36 weeks.
A single intravenous infusion of 260 mg ustekinumab (body weight ≤55 kilogram \[kg\]), 390 mg ustekinumab (body weight 55-85 kg), or 520 mg ustekinumab (body weight \>85 kg) was administered on Day 0, followed by subcutaneous injection of 90 mg ustekinumab every 8 weeks.
|
Placebo and Ustekinumab
n=25 Participants
Participants with moderately to severely active CD administered one dose of placebo matching BI 706321 as tablets orally once per day in the morning for 12 weeks in conjunction with standard induction dosing of ustekinumab, followed by ustekinumab maintenance dosing for an additional 36 weeks.
A single intravenous infusion of 260 mg ustekinumab (body weight ≤55 kilogram \[kg\]), 390 mg ustekinumab (body weight 55-85 kg), or 520 mg ustekinumab (body weight \>85 kg) was administered on Day 0, followed by subcutaneous injection of 90 mg ustekinumab every 8 weeks.
|
|---|---|---|
|
Percent Change in SES-CD From Baseline at Week 12
|
-14.18 Percent change
Interval -30.3 to 1.95
|
-27.52 Percent change
Interval -43.3 to -11.73
|
SECONDARY outcome
Timeframe: Within 28 days before randomization (baseline) and 12 weeks after first drug administration.Population: Full analysis set (FAS): all randomized patients who received at least 1 dose of trial medication and have analyzable post-baseline data (observed or imputed) in at least 1 efficacy/biological/histological parameter. If there were data at visits before and after one with a missing outcome, data was imputed as success only if both neighboring visits represented a success, independently of whether the before and after observations were selected for analysis based on the pre-defined time windows.
Percentage of patients with endoscopic response (defined as \>50% Simple Endoscopic Score for Crohn's disease (SES-CD) reduction from baseline, or for an induction baseline SES-CD of 4, at least a 2 point reduction from induction baseline) at Week 12 is reported. The SES-CD is a numerical grading system composed of 4 variables (presence of ulcers, ulcerated surface, affected surface, presence of narrowings) recorded sequentially in 5 segments: rectum, left colon, transverse colon, right colon, ileum. Each variable is assigned a value from 0 to 3, and the total score, ranging from 0 to 56, is obtained by adding each variable. Higher values indicate worse endoscopic inflammation. To achieve a score of 56, the maximum score for the "presence of narrowings" variable has to be be 2 (not 3) for the four segments leading up to the ileum. The method to provide confidence intervals for single proportions is based on the Wilson method.
Outcome measures
| Measure |
BI 706321 and Ustekinumab
n=24 Participants
Participants with moderately to severely active Crohn's Disease (CD) administered one dose of 8 milligram (mg) BI 706321 as tablets orally once per day in the morning for 12 weeks in conjunction with standard induction dosing of ustekinumab, followed by ustekinumab maintenance dosing for an additional 36 weeks.
A single intravenous infusion of 260 mg ustekinumab (body weight ≤55 kilogram \[kg\]), 390 mg ustekinumab (body weight 55-85 kg), or 520 mg ustekinumab (body weight \>85 kg) was administered on Day 0, followed by subcutaneous injection of 90 mg ustekinumab every 8 weeks.
|
Placebo and Ustekinumab
n=25 Participants
Participants with moderately to severely active CD administered one dose of placebo matching BI 706321 as tablets orally once per day in the morning for 12 weeks in conjunction with standard induction dosing of ustekinumab, followed by ustekinumab maintenance dosing for an additional 36 weeks.
A single intravenous infusion of 260 mg ustekinumab (body weight ≤55 kilogram \[kg\]), 390 mg ustekinumab (body weight 55-85 kg), or 520 mg ustekinumab (body weight \>85 kg) was administered on Day 0, followed by subcutaneous injection of 90 mg ustekinumab every 8 weeks.
|
|---|---|---|
|
Percentage of Patients With Endoscopic Response (Defined as >50% SES-CD Reduction From Baseline, or for an Induction Baseline SES-CD of 4, at Least a 2 Point Reduction From Induction Baseline) at Week 12
|
12.5 Percentage of patients
Interval 4.3 to 31.0
|
40.0 Percentage of patients
Interval 23.4 to 59.3
|
SECONDARY outcome
Timeframe: Within 28 days before randomization (baseline) and 48 weeks after first drug administration.Population: Full analysis set (FAS): all randomized patients who received at least 1 dose of trial medication and have analyzable post-baseline data (observed or imputed) in at least 1 efficacy/biological/histological parameter. If there were data at visits before and after one with a missing outcome, data was imputed as success only if both neighboring visits represented a success, independently of whether the before and after observations were selected for analysis based on the pre-defined time windows.
Percentage of patients with endoscopic response (defined as \>50% Simple Endoscopic Score for Crohn's disease (SES-CD) reduction from baseline, or for an induction baseline SES-CD of 4, at least a 2 point reduction from induction baseline) at Week 48 is reported. The SES-CD is a numerical grading system composed of 4 variables (presence of ulcers, ulcerated surface, affected surface, presence of narrowings) recorded sequentially in 5 segments: rectum, left colon, transverse colon, right colon, ileum. Each variable is assigned a value from 0 to 3, and the total score, ranging from 0 to 56, is obtained by adding each variable. Higher values indicate worse endoscopic inflammation. To achieve a score of 56, the maximum score for the "presence of narrowings" variable has to be be 2 (not 3) for the four segments leading up to the ileum. The method to provide confidence intervals for single proportions is based on the Wilson method.
Outcome measures
| Measure |
BI 706321 and Ustekinumab
n=24 Participants
Participants with moderately to severely active Crohn's Disease (CD) administered one dose of 8 milligram (mg) BI 706321 as tablets orally once per day in the morning for 12 weeks in conjunction with standard induction dosing of ustekinumab, followed by ustekinumab maintenance dosing for an additional 36 weeks.
A single intravenous infusion of 260 mg ustekinumab (body weight ≤55 kilogram \[kg\]), 390 mg ustekinumab (body weight 55-85 kg), or 520 mg ustekinumab (body weight \>85 kg) was administered on Day 0, followed by subcutaneous injection of 90 mg ustekinumab every 8 weeks.
|
Placebo and Ustekinumab
n=25 Participants
Participants with moderately to severely active CD administered one dose of placebo matching BI 706321 as tablets orally once per day in the morning for 12 weeks in conjunction with standard induction dosing of ustekinumab, followed by ustekinumab maintenance dosing for an additional 36 weeks.
A single intravenous infusion of 260 mg ustekinumab (body weight ≤55 kilogram \[kg\]), 390 mg ustekinumab (body weight 55-85 kg), or 520 mg ustekinumab (body weight \>85 kg) was administered on Day 0, followed by subcutaneous injection of 90 mg ustekinumab every 8 weeks.
|
|---|---|---|
|
Percentage of Patients With Endoscopic Response (Defined as >50% SES-CD Reduction From Baseline, or for an Induction Baseline SES-CD of 4, at Least a 2 Point Reduction From Induction Baseline) at Week 48
|
16.7 Percentage of patients
Interval 6.7 to 35.9
|
16.0 Percentage of patients
Interval 6.4 to 34.7
|
SECONDARY outcome
Timeframe: 12 weeks after first drug administration.Population: Full analysis set (FAS): all randomized patients who received at least 1 dose of trial medication and have analyzable post-baseline data (observed or imputed) in at least 1 efficacy/biological/histological parameter. If there were data at visits before and after one with a missing outcome, data was imputed as success only if both neighboring visits represented a success, independently of whether the before and after observations were selected for analysis based on the pre-defined time windows.
Percentage of patients with endoscopic remission (defined as Simple Endoscopic Score for Crohn's disease (SES-CD) score of ≤2) at Week 12 is reported. The SES-CD is a numerical grading system composed of 4 variables (presence of ulcers, ulcerated surface, affected surface, presence of narrowings) recorded sequentially in 5 segments: rectum, left colon, transverse colon, right colon, ileum. Each variable is assigned a value from 0 to 3, and the total score, ranging from 0 to 56, is obtained by adding each variable. Higher values indicate worse endoscopic inflammation. To achieve a score of 56, the maximum score for the "presence of narrowings" variable has to be be 2 (not 3) for the four segments leading up to the ileum. The method to provide confidence intervals for single proportions is based on the Wilson method.
Outcome measures
| Measure |
BI 706321 and Ustekinumab
n=24 Participants
Participants with moderately to severely active Crohn's Disease (CD) administered one dose of 8 milligram (mg) BI 706321 as tablets orally once per day in the morning for 12 weeks in conjunction with standard induction dosing of ustekinumab, followed by ustekinumab maintenance dosing for an additional 36 weeks.
A single intravenous infusion of 260 mg ustekinumab (body weight ≤55 kilogram \[kg\]), 390 mg ustekinumab (body weight 55-85 kg), or 520 mg ustekinumab (body weight \>85 kg) was administered on Day 0, followed by subcutaneous injection of 90 mg ustekinumab every 8 weeks.
|
Placebo and Ustekinumab
n=25 Participants
Participants with moderately to severely active CD administered one dose of placebo matching BI 706321 as tablets orally once per day in the morning for 12 weeks in conjunction with standard induction dosing of ustekinumab, followed by ustekinumab maintenance dosing for an additional 36 weeks.
A single intravenous infusion of 260 mg ustekinumab (body weight ≤55 kilogram \[kg\]), 390 mg ustekinumab (body weight 55-85 kg), or 520 mg ustekinumab (body weight \>85 kg) was administered on Day 0, followed by subcutaneous injection of 90 mg ustekinumab every 8 weeks.
|
|---|---|---|
|
Percentage of Patients With Endoscopic Remission (Defined as SES-CD Score of ≤2) at Week 12
|
4.2 Percentage of patients
Interval 0.7 to 20.2
|
8.0 Percentage of patients
Interval 2.2 to 25.0
|
SECONDARY outcome
Timeframe: 48 weeks after first drug administration.Population: Full analysis set (FAS): all randomized patients who received at least 1 dose of trial medication and have analyzable post-baseline data (observed or imputed) in at least 1 efficacy/biological/histological parameter. If there were data at visits before and after one with a missing outcome, data was imputed as success only if both neighboring visits represented a success, independently of whether the before and after observations were selected for analysis based on the pre-defined time windows.
Percentage of patients with endoscopic remission (defined as Simple Endoscopic Score for Crohn's disease (SES-CD) score of ≤2) at Week 48 is reported. The SES-CD is a numerical grading system composed of 4 variables (presence of ulcers, ulcerated surface, affected surface, presence of narrowings) recorded sequentially in 5 segments: rectum, left colon, transverse colon, right colon, ileum. Each variable is assigned a value from 0 to 3, and the total score, ranging from 0 to 56, is obtained by adding each variable. Higher values indicate worse endoscopic inflammation. To achieve a score of 56, the maximum score for the "presence of narrowings" variable has to be be 2 (not 3) for the four segments leading up to the ileum. The method to provide confidence intervals for single proportions is based on the Wilson method.
Outcome measures
| Measure |
BI 706321 and Ustekinumab
n=24 Participants
Participants with moderately to severely active Crohn's Disease (CD) administered one dose of 8 milligram (mg) BI 706321 as tablets orally once per day in the morning for 12 weeks in conjunction with standard induction dosing of ustekinumab, followed by ustekinumab maintenance dosing for an additional 36 weeks.
A single intravenous infusion of 260 mg ustekinumab (body weight ≤55 kilogram \[kg\]), 390 mg ustekinumab (body weight 55-85 kg), or 520 mg ustekinumab (body weight \>85 kg) was administered on Day 0, followed by subcutaneous injection of 90 mg ustekinumab every 8 weeks.
|
Placebo and Ustekinumab
n=25 Participants
Participants with moderately to severely active CD administered one dose of placebo matching BI 706321 as tablets orally once per day in the morning for 12 weeks in conjunction with standard induction dosing of ustekinumab, followed by ustekinumab maintenance dosing for an additional 36 weeks.
A single intravenous infusion of 260 mg ustekinumab (body weight ≤55 kilogram \[kg\]), 390 mg ustekinumab (body weight 55-85 kg), or 520 mg ustekinumab (body weight \>85 kg) was administered on Day 0, followed by subcutaneous injection of 90 mg ustekinumab every 8 weeks.
|
|---|---|---|
|
Percentage of Patients With Endoscopic Remission (Defined as SES-CD Score of ≤2) at Week 48
|
8.3 Percentage of patients
Interval 2.3 to 25.8
|
8.0 Percentage of patients
Interval 2.2 to 25.0
|
SECONDARY outcome
Timeframe: 12 weeks after first drug administration.Population: Full analysis set (FAS): all randomized patients who received at least 1 dose of trial medication and have analyzable post-baseline data (observed or imputed) in at least 1 efficacy/biological/histological parameter. If there were data at visits before and after one with a missing outcome, data was imputed as success only if both neighboring visits represented a success, independently of whether the before and after observations were selected for analysis based on the pre-defined time windows.
Percentage of patients with biological remission, defined as C-Reactive Protein (CRP) \< 5 mg/L and faecal calprotectin (FCP) \< 250 ug/g at Week 12 is reported. The method to provide confidence intervals for single proportions is based on the Wilson method.
Outcome measures
| Measure |
BI 706321 and Ustekinumab
n=24 Participants
Participants with moderately to severely active Crohn's Disease (CD) administered one dose of 8 milligram (mg) BI 706321 as tablets orally once per day in the morning for 12 weeks in conjunction with standard induction dosing of ustekinumab, followed by ustekinumab maintenance dosing for an additional 36 weeks.
A single intravenous infusion of 260 mg ustekinumab (body weight ≤55 kilogram \[kg\]), 390 mg ustekinumab (body weight 55-85 kg), or 520 mg ustekinumab (body weight \>85 kg) was administered on Day 0, followed by subcutaneous injection of 90 mg ustekinumab every 8 weeks.
|
Placebo and Ustekinumab
n=25 Participants
Participants with moderately to severely active CD administered one dose of placebo matching BI 706321 as tablets orally once per day in the morning for 12 weeks in conjunction with standard induction dosing of ustekinumab, followed by ustekinumab maintenance dosing for an additional 36 weeks.
A single intravenous infusion of 260 mg ustekinumab (body weight ≤55 kilogram \[kg\]), 390 mg ustekinumab (body weight 55-85 kg), or 520 mg ustekinumab (body weight \>85 kg) was administered on Day 0, followed by subcutaneous injection of 90 mg ustekinumab every 8 weeks.
|
|---|---|---|
|
Percentage of Patients With Biological Remission, Defined as C-Reactive Protein (CRP) < 5 mg/L and Faecal Calprotectin (FCP) < 250 ug/g at Week 12
|
16.7 Percentage of patients
Interval 6.7 to 35.9
|
20.0 Percentage of patients
Interval 8.9 to 39.1
|
SECONDARY outcome
Timeframe: 48 weeks after first drug administration.Population: Full analysis set (FAS): all randomized patients who received at least 1 dose of trial medication and have analyzable post-baseline data (observed or imputed) in at least 1 efficacy/biological/histological parameter. If there were data at visits before and after one with a missing outcome, data was imputed as success only if both neighboring visits represented a success, independently of whether the before and after observations were selected for analysis based on the pre-defined time windows.
Percentage of patients with biological remission, defined as C-Reactive Protein (CRP) \< 5 mg/L and faecal calprotectin (FCP) \< 250 ug/g at Week 48 is reported. The method to provide confidence intervals for single proportions is based on the Wilson method.
Outcome measures
| Measure |
BI 706321 and Ustekinumab
n=24 Participants
Participants with moderately to severely active Crohn's Disease (CD) administered one dose of 8 milligram (mg) BI 706321 as tablets orally once per day in the morning for 12 weeks in conjunction with standard induction dosing of ustekinumab, followed by ustekinumab maintenance dosing for an additional 36 weeks.
A single intravenous infusion of 260 mg ustekinumab (body weight ≤55 kilogram \[kg\]), 390 mg ustekinumab (body weight 55-85 kg), or 520 mg ustekinumab (body weight \>85 kg) was administered on Day 0, followed by subcutaneous injection of 90 mg ustekinumab every 8 weeks.
|
Placebo and Ustekinumab
n=25 Participants
Participants with moderately to severely active CD administered one dose of placebo matching BI 706321 as tablets orally once per day in the morning for 12 weeks in conjunction with standard induction dosing of ustekinumab, followed by ustekinumab maintenance dosing for an additional 36 weeks.
A single intravenous infusion of 260 mg ustekinumab (body weight ≤55 kilogram \[kg\]), 390 mg ustekinumab (body weight 55-85 kg), or 520 mg ustekinumab (body weight \>85 kg) was administered on Day 0, followed by subcutaneous injection of 90 mg ustekinumab every 8 weeks.
|
|---|---|---|
|
Percentage of Patients With Biological Remission, Defined as C-Reactive Protein (CRP) < 5 mg/L and Faecal Calprotectin (FCP) < 250 ug/g at Week 48
|
12.5 Percentage of patients
Interval 4.3 to 31.0
|
16.0 Percentage of patients
Interval 6.4 to 34.7
|
SECONDARY outcome
Timeframe: Data was collected for 7 days prior to 12 weeks after first drug administration.Population: Full analysis set (FAS): all randomized patients who received at least 1 dose of trial medication and have analyzable post-baseline data (observed or imputed) in at least 1 efficacy/biological/histological parameter. If there were data at visits before and after one with a missing outcome, data was imputed as success only if both neighboring visits represented a success, independently of whether the before and after observations were selected for analysis based on the pre-defined time windows.
Percentage of patients with clinical remission at Week 12, defined as a Crohn's Disease Activity Index (CDAI) score of \<150 is reported. The CDAI is comprised of eight variables which are summed after adjustment with a weighting factor, and the total score ranges from 0 to approximately 600, with higher scores indicating more severe disease. For certain variables (daily number of liquid or very soft stools, daily abdominal pain, daily general well-being, fever over 37.8 Celsius, taking medication for diarrhea) the average over 7 days was taken. The method to provide confidence intervals for single proportions is based on the Wilson method.
Outcome measures
| Measure |
BI 706321 and Ustekinumab
n=24 Participants
Participants with moderately to severely active Crohn's Disease (CD) administered one dose of 8 milligram (mg) BI 706321 as tablets orally once per day in the morning for 12 weeks in conjunction with standard induction dosing of ustekinumab, followed by ustekinumab maintenance dosing for an additional 36 weeks.
A single intravenous infusion of 260 mg ustekinumab (body weight ≤55 kilogram \[kg\]), 390 mg ustekinumab (body weight 55-85 kg), or 520 mg ustekinumab (body weight \>85 kg) was administered on Day 0, followed by subcutaneous injection of 90 mg ustekinumab every 8 weeks.
|
Placebo and Ustekinumab
n=25 Participants
Participants with moderately to severely active CD administered one dose of placebo matching BI 706321 as tablets orally once per day in the morning for 12 weeks in conjunction with standard induction dosing of ustekinumab, followed by ustekinumab maintenance dosing for an additional 36 weeks.
A single intravenous infusion of 260 mg ustekinumab (body weight ≤55 kilogram \[kg\]), 390 mg ustekinumab (body weight 55-85 kg), or 520 mg ustekinumab (body weight \>85 kg) was administered on Day 0, followed by subcutaneous injection of 90 mg ustekinumab every 8 weeks.
|
|---|---|---|
|
Percentage of Patients With Clinical Remission at Week 12, Defined as a Crohn's Disease Activity Index (CDAI) Score of <150
|
37.5 Percentage of patients
Interval 21.2 to 57.3
|
56.0 Percentage of patients
Interval 37.1 to 73.3
|
SECONDARY outcome
Timeframe: Data was collected for 7 days prior to 48 weeks after first drug administration.Population: Full analysis set (FAS): all randomized patients who received at least 1 dose of trial medication and have analyzable post-baseline data (observed or imputed) in at least 1 efficacy/biological/histological parameter. If there were data at visits before and after one with a missing outcome, data was imputed as success only if both neighboring visits represented a success, independently of whether the before and after observations were selected for analysis based on the pre-defined time windows.
Percentage of patients with clinical remission at Week 48, defined as a CDAI score of \<150 is reported. The CDAI is comprised of eight variables which are summed after adjustment with a weighting factor, and the total score ranges from 0 to approximately 600, with higher scores indicating more severe disease. For certain variables (daily number of liquid or very soft stools, daily abdominal pain, daily general well-being, fever over 37.8 Celsius, taking medication for diarrhea) the average over 7 days was taken. The method to provide confidence intervals for single proportions is based on the Wilson method.
Outcome measures
| Measure |
BI 706321 and Ustekinumab
n=24 Participants
Participants with moderately to severely active Crohn's Disease (CD) administered one dose of 8 milligram (mg) BI 706321 as tablets orally once per day in the morning for 12 weeks in conjunction with standard induction dosing of ustekinumab, followed by ustekinumab maintenance dosing for an additional 36 weeks.
A single intravenous infusion of 260 mg ustekinumab (body weight ≤55 kilogram \[kg\]), 390 mg ustekinumab (body weight 55-85 kg), or 520 mg ustekinumab (body weight \>85 kg) was administered on Day 0, followed by subcutaneous injection of 90 mg ustekinumab every 8 weeks.
|
Placebo and Ustekinumab
n=25 Participants
Participants with moderately to severely active CD administered one dose of placebo matching BI 706321 as tablets orally once per day in the morning for 12 weeks in conjunction with standard induction dosing of ustekinumab, followed by ustekinumab maintenance dosing for an additional 36 weeks.
A single intravenous infusion of 260 mg ustekinumab (body weight ≤55 kilogram \[kg\]), 390 mg ustekinumab (body weight 55-85 kg), or 520 mg ustekinumab (body weight \>85 kg) was administered on Day 0, followed by subcutaneous injection of 90 mg ustekinumab every 8 weeks.
|
|---|---|---|
|
Percentage of Patients With Clinical Remission at Week 48, Defined as a CDAI Score of <150
|
20.8 Percentage of patients
Interval 9.2 to 40.5
|
20.0 Percentage of patients
Interval 8.9 to 39.1
|
SECONDARY outcome
Timeframe: Within 28 days before randomization (baseline) and for 7 days prior to 12 weeks after first drug administration.Population: Full analysis set (FAS): all randomized patients who received at least 1 dose of trial medication and have analyzable post-baseline data (observed or imputed) in at least 1 efficacy/biological/histological parameter. If there were data at visits before and after one with a missing outcome, data was imputed as success only if both neighboring visits represented a success, independently of whether the before and after observations were selected for analysis based on the pre-defined time windows.
Percentage of patients with clinical response at Week 12, defined by a CDAI reduction from baseline of at least 100 points, or a CDAI score of \<150 is reported. The CDAI is comprised of eight variables which are summed after adjustment with a weighting factor, and the total score ranges from 0 to approximately 600, with higher scores indicating more severe disease. For certain variables (daily number of liquid or very soft stools, daily abdominal pain, daily general well-being, fever over 37.8 Celsius, taking medication for diarrhea) the average over 7 days was taken. The method to provide confidence intervals for single proportions is based on the Wilson method.
Outcome measures
| Measure |
BI 706321 and Ustekinumab
n=24 Participants
Participants with moderately to severely active Crohn's Disease (CD) administered one dose of 8 milligram (mg) BI 706321 as tablets orally once per day in the morning for 12 weeks in conjunction with standard induction dosing of ustekinumab, followed by ustekinumab maintenance dosing for an additional 36 weeks.
A single intravenous infusion of 260 mg ustekinumab (body weight ≤55 kilogram \[kg\]), 390 mg ustekinumab (body weight 55-85 kg), or 520 mg ustekinumab (body weight \>85 kg) was administered on Day 0, followed by subcutaneous injection of 90 mg ustekinumab every 8 weeks.
|
Placebo and Ustekinumab
n=25 Participants
Participants with moderately to severely active CD administered one dose of placebo matching BI 706321 as tablets orally once per day in the morning for 12 weeks in conjunction with standard induction dosing of ustekinumab, followed by ustekinumab maintenance dosing for an additional 36 weeks.
A single intravenous infusion of 260 mg ustekinumab (body weight ≤55 kilogram \[kg\]), 390 mg ustekinumab (body weight 55-85 kg), or 520 mg ustekinumab (body weight \>85 kg) was administered on Day 0, followed by subcutaneous injection of 90 mg ustekinumab every 8 weeks.
|
|---|---|---|
|
Percentage of Patients With Clinical Response at Week 12, Defined by a CDAI Reduction From Baseline of at Least 100 Points, or a CDAI Score of <150
|
45.8 Percentage of patients
Interval 27.9 to 64.9
|
68.0 Percentage of patients
Interval 48.4 to 82.8
|
SECONDARY outcome
Timeframe: From first drug administration until 16 days after last drug administration, up to 27 weeks.Population: Full analysis set (FAS): all randomized patients who received at least 1 dose of trial medication and have analyzable post-baseline data (observed or imputed) in at least 1 efficacy/biological/histological parameter.
Number of patients with treatment-emergent adverse event (TEAE) through end of treatment (EoT) and the REP period is reported.
Outcome measures
| Measure |
BI 706321 and Ustekinumab
n=24 Participants
Participants with moderately to severely active Crohn's Disease (CD) administered one dose of 8 milligram (mg) BI 706321 as tablets orally once per day in the morning for 12 weeks in conjunction with standard induction dosing of ustekinumab, followed by ustekinumab maintenance dosing for an additional 36 weeks.
A single intravenous infusion of 260 mg ustekinumab (body weight ≤55 kilogram \[kg\]), 390 mg ustekinumab (body weight 55-85 kg), or 520 mg ustekinumab (body weight \>85 kg) was administered on Day 0, followed by subcutaneous injection of 90 mg ustekinumab every 8 weeks.
|
Placebo and Ustekinumab
n=25 Participants
Participants with moderately to severely active CD administered one dose of placebo matching BI 706321 as tablets orally once per day in the morning for 12 weeks in conjunction with standard induction dosing of ustekinumab, followed by ustekinumab maintenance dosing for an additional 36 weeks.
A single intravenous infusion of 260 mg ustekinumab (body weight ≤55 kilogram \[kg\]), 390 mg ustekinumab (body weight 55-85 kg), or 520 mg ustekinumab (body weight \>85 kg) was administered on Day 0, followed by subcutaneous injection of 90 mg ustekinumab every 8 weeks.
|
|---|---|---|
|
Number of Patients With Treatment-emergent Adverse Event (TEAE) Through End of Treatment (EoT) and the REP Period
|
11 Participants
|
12 Participants
|
Adverse Events
BI 706321 and Ustekinumab
Placebo and Ustekinumab
Serious adverse events
| Measure |
BI 706321 and Ustekinumab
n=24 participants at risk
Participants with moderately to severely active Crohn's Disease (CD) administered one dose of 8 milligram (mg) BI 706321 as tablets orally once per day in the morning for 12 weeks in conjunction with standard induction dosing of ustekinumab, followed by ustekinumab maintenance dosing for an additional 36 weeks.
A single intravenous infusion of 260 mg ustekinumab (body weight ≤55 kilogram \[kg\]), 390 mg ustekinumab (body weight 55-85 kg), or 520 mg ustekinumab (body weight \>85 kg) was administered on Day 0, followed by subcutaneous injection of 90 mg ustekinumab every 8 weeks.
|
Placebo and Ustekinumab
n=25 participants at risk
Participants with moderately to severely active CD administered one dose of placebo matching BI 706321 as tablets orally once per day in the morning for 12 weeks in conjunction with standard induction dosing of ustekinumab, followed by ustekinumab maintenance dosing for an additional 36 weeks.
A single intravenous infusion of 260 mg ustekinumab (body weight ≤55 kilogram \[kg\]), 390 mg ustekinumab (body weight 55-85 kg), or 520 mg ustekinumab (body weight \>85 kg) was administered on Day 0, followed by subcutaneous injection of 90 mg ustekinumab every 8 weeks.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/24 • From first drug administration, until end of follow-up period, up to 48 weeks.
Full analysis set (FAS): all randomized patients who received at least 1 dose of trial medication and have analyzable post-baseline data (observed or imputed) in at least 1 efficacy/biological/histological parameter.
|
4.0%
1/25 • From first drug administration, until end of follow-up period, up to 48 weeks.
Full analysis set (FAS): all randomized patients who received at least 1 dose of trial medication and have analyzable post-baseline data (observed or imputed) in at least 1 efficacy/biological/histological parameter.
|
|
Gastrointestinal disorders
Crohn's disease
|
4.2%
1/24 • From first drug administration, until end of follow-up period, up to 48 weeks.
Full analysis set (FAS): all randomized patients who received at least 1 dose of trial medication and have analyzable post-baseline data (observed or imputed) in at least 1 efficacy/biological/histological parameter.
|
0.00%
0/25 • From first drug administration, until end of follow-up period, up to 48 weeks.
Full analysis set (FAS): all randomized patients who received at least 1 dose of trial medication and have analyzable post-baseline data (observed or imputed) in at least 1 efficacy/biological/histological parameter.
|
|
Musculoskeletal and connective tissue disorders
Enthesopathy
|
4.2%
1/24 • From first drug administration, until end of follow-up period, up to 48 weeks.
Full analysis set (FAS): all randomized patients who received at least 1 dose of trial medication and have analyzable post-baseline data (observed or imputed) in at least 1 efficacy/biological/histological parameter.
|
0.00%
0/25 • From first drug administration, until end of follow-up period, up to 48 weeks.
Full analysis set (FAS): all randomized patients who received at least 1 dose of trial medication and have analyzable post-baseline data (observed or imputed) in at least 1 efficacy/biological/histological parameter.
|
Other adverse events
| Measure |
BI 706321 and Ustekinumab
n=24 participants at risk
Participants with moderately to severely active Crohn's Disease (CD) administered one dose of 8 milligram (mg) BI 706321 as tablets orally once per day in the morning for 12 weeks in conjunction with standard induction dosing of ustekinumab, followed by ustekinumab maintenance dosing for an additional 36 weeks.
A single intravenous infusion of 260 mg ustekinumab (body weight ≤55 kilogram \[kg\]), 390 mg ustekinumab (body weight 55-85 kg), or 520 mg ustekinumab (body weight \>85 kg) was administered on Day 0, followed by subcutaneous injection of 90 mg ustekinumab every 8 weeks.
|
Placebo and Ustekinumab
n=25 participants at risk
Participants with moderately to severely active CD administered one dose of placebo matching BI 706321 as tablets orally once per day in the morning for 12 weeks in conjunction with standard induction dosing of ustekinumab, followed by ustekinumab maintenance dosing for an additional 36 weeks.
A single intravenous infusion of 260 mg ustekinumab (body weight ≤55 kilogram \[kg\]), 390 mg ustekinumab (body weight 55-85 kg), or 520 mg ustekinumab (body weight \>85 kg) was administered on Day 0, followed by subcutaneous injection of 90 mg ustekinumab every 8 weeks.
|
|---|---|---|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/24 • From first drug administration, until end of follow-up period, up to 48 weeks.
Full analysis set (FAS): all randomized patients who received at least 1 dose of trial medication and have analyzable post-baseline data (observed or imputed) in at least 1 efficacy/biological/histological parameter.
|
8.0%
2/25 • From first drug administration, until end of follow-up period, up to 48 weeks.
Full analysis set (FAS): all randomized patients who received at least 1 dose of trial medication and have analyzable post-baseline data (observed or imputed) in at least 1 efficacy/biological/histological parameter.
|
|
General disorders
Fatigue
|
0.00%
0/24 • From first drug administration, until end of follow-up period, up to 48 weeks.
Full analysis set (FAS): all randomized patients who received at least 1 dose of trial medication and have analyzable post-baseline data (observed or imputed) in at least 1 efficacy/biological/histological parameter.
|
8.0%
2/25 • From first drug administration, until end of follow-up period, up to 48 weeks.
Full analysis set (FAS): all randomized patients who received at least 1 dose of trial medication and have analyzable post-baseline data (observed or imputed) in at least 1 efficacy/biological/histological parameter.
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/24 • From first drug administration, until end of follow-up period, up to 48 weeks.
Full analysis set (FAS): all randomized patients who received at least 1 dose of trial medication and have analyzable post-baseline data (observed or imputed) in at least 1 efficacy/biological/histological parameter.
|
8.0%
2/25 • From first drug administration, until end of follow-up period, up to 48 weeks.
Full analysis set (FAS): all randomized patients who received at least 1 dose of trial medication and have analyzable post-baseline data (observed or imputed) in at least 1 efficacy/biological/histological parameter.
|
|
Infections and infestations
Rhinitis
|
0.00%
0/24 • From first drug administration, until end of follow-up period, up to 48 weeks.
Full analysis set (FAS): all randomized patients who received at least 1 dose of trial medication and have analyzable post-baseline data (observed or imputed) in at least 1 efficacy/biological/histological parameter.
|
8.0%
2/25 • From first drug administration, until end of follow-up period, up to 48 weeks.
Full analysis set (FAS): all randomized patients who received at least 1 dose of trial medication and have analyzable post-baseline data (observed or imputed) in at least 1 efficacy/biological/histological parameter.
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/24 • From first drug administration, until end of follow-up period, up to 48 weeks.
Full analysis set (FAS): all randomized patients who received at least 1 dose of trial medication and have analyzable post-baseline data (observed or imputed) in at least 1 efficacy/biological/histological parameter.
|
8.0%
2/25 • From first drug administration, until end of follow-up period, up to 48 weeks.
Full analysis set (FAS): all randomized patients who received at least 1 dose of trial medication and have analyzable post-baseline data (observed or imputed) in at least 1 efficacy/biological/histological parameter.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/24 • From first drug administration, until end of follow-up period, up to 48 weeks.
Full analysis set (FAS): all randomized patients who received at least 1 dose of trial medication and have analyzable post-baseline data (observed or imputed) in at least 1 efficacy/biological/histological parameter.
|
8.0%
2/25 • From first drug administration, until end of follow-up period, up to 48 weeks.
Full analysis set (FAS): all randomized patients who received at least 1 dose of trial medication and have analyzable post-baseline data (observed or imputed) in at least 1 efficacy/biological/histological parameter.
|
Additional Information
Boehringer Ingelheim, Call Center
Boehringer Ingelheim
Results disclosure agreements
- Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER