NCT04978493 - A Study to Test Whether BI 706321 Combined With Ustekinumab Helps People With Crohn's Disease | Crick

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Diagnosis of Crohn Disease (CD) for at least 3 months prior to visit 1, as confirmed at any time in the past by endoscopy and/OR, radiology, and supported by histology. * Elevated C-reactive protein (≥ 5 mg/L) OR elevated fecal calprotectin (≥ 250 µg/g) * Symptomatic CD defined as Crohn's Disease Activity Index (CDAI) ≥150. * Presence of mucosal ulcers in at least one segment of the ileum or colon and a Simple Endoscopic Score for Crohn's disease (SES-CD) score ≥ 7 (for patients with isolated ileitis ≥4). * Patients who are experienced at least 1 tumor necrosis factor (TNF) antagonists at a dose approved for CD. Patients may have stopped TNF antagonist treatment due to primary or secondary non-responsiveness, intolerance, or for other reasons. * May be receiving a therapeutic dose of the following: * Oral 5-aminosalicylic acid (5-ASA) compounds must have been at a stable dose for at least 4 weeks prior to randomisation and must continue on this dose until week 12 and/or * Oral corticosteroids if indicated for treatment of CD must be at a prednisone equivalent dose of ≤ 20 mg/day, or ≤ 9 mg/day of budesonide, and have been at a stable dose for at least 2 weeks immediately prior to randomisation and must continue on this dose until week 12. and/or * Azathioprine (AZA), mercaptopurine (MP), or methotrexate (MTX), provided that dose has been stable for the 8 weeks immediately prior to randomisation and must continue on this dose until week 12. * Women of childbearing potential must be ready and able to use highly effective methods of birth control. * Further inclusion criteria apply Exclusion Criteria: * Have any current or prior abscesses, unless they have been drained and treated at least 6 weeks prior to randomisation and are not anticipated to require surgery. Patients with active fistulas may be included if there is no anticipation of a need for surgery and there are currently no abscesses present based on investigator's judgement. * Have complications of CD such as strictures, stenosis, short bowel syndrome, or any other manifestation that might require surgery, or could preclude the use of SES-CD/CDAI to assess response to therapy, or would possibly confound the evaluation of benefit from treatment with BI 706321 (based on investigator's judgement). * Patient with an inflammatory bowel disease (IBD) diagnosis other than CD. * Have had any kind of bowel resection or diversion within 4 months or any other intra-abdominal surgery within 3 months prior to visit 1. Patients with current ileostomy, colostomy, or ileorectal anastomosis are excluded. * Treatment with: * Any non-biologic medication for IBD (e.g.tacrolimus or mycophenolate mofetil, systemic corticosteroids), other than those allowed per inclusion criteria, within 30 days prior to randomisation * Any biologic treatment with a TNF-alpha antagonist (adalimumab, infliximab, golimumab, certolizumab pegol) or vedolizumab (or a biosimilar of these drugs) within 4 weeks prior to randomisation. (If drug level testing for previously used biologic treatment confirms no detectable drug level before randomisation, patient can be enrolled despite not having completed 4 week from last treatment.) * Any previous treatment with ustekinumab (or a biosimilar of this drug) * Any previous treatment with an investigational (or subsequently approved) non-biologic/biologic drug for CD (including but not limited to JAK inhibitors \[e.g. upadacitinib\], S1P modulators, IL-23 inhibitors \[e.g. risankizumab\], antiintegrins). * Any investigational drug for an indication other than CD during the course of the actual study and within 30 days or 5 half-lives (whichever is longer) prior to randomisation. * Any prior exposure to rituximab within 1 year prior to randomisation. * Positive stool examination for C difficile or other intestinal pathogens \<30 days prior to randomization * Evidence of colonic moderate/severe mucosal dysplasia or colonic adenomas, unless properly removed * Increased risk of infectious complications (e.g. recent pyogenic infection, any congenital or acquired immunodeficiency (e.g. human immunodeficiency virus (HIV)), past organ or stem cell transplantation (with exception of a corneal transplant \> 12 weeks prior to screening) or have ever received stem cell therapy (e.g., Prochymal). Prior treatment with a somatic cell therapy product (e.g., Alofisel) is not excluded, provided it was administered \> 8 weeks prior to randomisation. * Live or attenuated vaccination within 4 weeks prior to randomisation. * Presence of clinically significant acute or chronic infections not otherwise listed, including viral hepatitis, COVID-19, or others based on investigator's judgement. * A marked baseline prolongation of QT/QTc interval (such as QTcF intervals that are greater than 450 ms for men, 470 ms for female) or any other relevant electrocardiogram (ECG) finding at screening. Both have to be confirmed by repeated ECG recording. * Further exclusion criteria apply

Outcomes

Primary Outcomes

Absolute Change From Baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD) at Week 12

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.

Time frame: Within 28 days before randomization (baseline) and 12 weeks after first drug administration.

Secondary Outcomes

Percent Change in SES-CD From Baseline at Week 12

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.

Time frame: Within 28 days before randomization (baseline) and 12 weeks after first drug administration.

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

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.

Time frame: Within 28 days before randomization (baseline) and 12 weeks after first drug administration.

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.

Time frame: Within 28 days before randomization (baseline) and 48 weeks after first drug administration.

Percentage of Patients With Endoscopic Remission (Defined as SES-CD Score of ≤2) at Week 12

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.

Time frame: 12 weeks after first drug administration.

Percentage of Patients With Endoscopic Remission (Defined as SES-CD Score of ≤2) at Week 48

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.

Time frame: 48 weeks after first drug administration.

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

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.

Time frame: 12 weeks after first drug administration.

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

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.

Time frame: 48 weeks after first drug administration.

Percentage of Patients With Clinical Remission at Week 12, Defined as a Crohn's Disease Activity Index (CDAI) Score of <150

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.

Time frame: Data was collected for 7 days prior to 12 weeks after first drug administration.

Percentage of Patients With Clinical Remission at Week 48, Defined as a CDAI Score of <150

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.

Time frame: Data was collected for 7 days prior to 48 weeks after first drug administration.

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

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.

Time frame: Within 28 days before randomization (baseline) and for 7 days prior to 12 weeks after first drug administration.

Number of Patients With Treatment-emergent Adverse Event (TEAE) Through End of Treatment (EoT) and the REP Period

Number of patients with treatment-emergent adverse event (TEAE) through end of treatment (EoT) and the REP period is reported.

Time frame: From first drug administration until 16 days after last drug administration, up to 27 weeks.

A Study to Test Whether BI 706321 Combined With Ustekinumab Helps People With Crohn's Disease

Overview

Conditions

Interventions

Eligibility

Locations (49)

Outcomes

Primary Outcomes

Secondary Outcomes