A study to test whether BI 706321 combined with ustekinumab helps people with Crohn’s Disease (InCharge)
The purpose of this trial is to:
- To investigate how well the treatment with trial drug BI 706321 (in addition to ustekinumab) can improve the symptoms of CD
- To investigate the safety of BI 706321 and how you tolerate BI 706321
- To collect your blood and assess the amount of BI 706321 in the body (called pharmacokinetics or PK, meaning how your body absorbs and distributes BI 706321 and how BI 706321 leaves the body) and biomarkers (how other proteins in your body are influenced by BI 706321).
- 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 to 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
- Have any current or prior abscesses, unless they have been drained and treated at least 6 weeks prior to randomization 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 randomization
- Any biologic treatment with a TNF-alpha antagonist (adalimumab, infliximab, golimumab, certolizumab pegol) or vedolizumab within 4 weeks prior to randomization.
- Any previous treatment with ustekinumab
- Any previous treatment with an investigational nonbiologic or biologic drug for CD (including but not limited to JAK inhibitors, S1P modulators, interleukin (IL)-23 inhibitors, anti-integrins).
- 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 randomization.
- Any prior exposure to rituximab within 1 year prior to randomization.
- 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 randomization.
- Live or attenuated vaccination within 4 weeks prior to randomization.
- 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
Study description/explanation of participation:
The purpose of this study is to find out whether BI 706321 combined with ustekinumab helps people with Crohn's disease. BI 706321 is a medicine being developed to treat Crohn's disease. Ustekinumab is a medicine already used to treat Crohn's disease.
Participants are put into 2 groups randomly, which means by chance. One group gets BI 706321 and ustekinumab. The other group gets placebo and ustekinumab.
Participants are in the study for about 1 year. During this time, they visit the study site about 13 times. At 3 of the visits, doctors do a colonoscopy to examine the bowel. The results from the colonoscopies are compared between the 2 groups. The doctors also regularly check participants' health and take note of any unwanted effects.
Description of treatment or intervention (mechanism of action):
Participants take BI 706321 or placebo as tablets every day as well as commercially available medication. BI 706321 is a kinase inhibitor which is intended to blunt the inflammatory response to microbiome in the gut.
Possible risks and side effects:
There may be risks to taking part in any clinical trial. For this Study, risks may include those related to the trial drug (BI 706321), the commercially available drug and study procedures. Before you join the clinical trial, you will receive a detailed patient information sheet where these risks are outlined and described. You will be able to discuss any risks and benefits of this Study with the investigator.