BI 706321 + Ustekinumab for Crohn's Disease

No longer recruiting at 92 trial locations

Overseen By Boehringer Ingelheim

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Boehringer Ingelheim

Must be taking: 5-ASA, Corticosteroids, Azathioprine

Must not be taking: Tacrolimus, Mycophenolate, Biologics

Disqualifiers: Abscesses, Bowel surgery, Other IBD, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 13

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a new medicine, BI 706321, combined with ustekinumab, can help people with moderate to severe Crohn's disease. Ustekinumab is already used for Crohn's, while BI 706321 is still in development. Participants will receive either both medicines or ustekinumab with a placebo (a pill that resembles the medicine but contains no active ingredients). The trial targets individuals who have had Crohn's disease symptoms for at least three months and have experienced issues like bowel ulcers or have tried other treatments without success. Participants will be involved in the study for about a year, with regular health check-ups and colonoscopies to monitor progress. As a Phase 2 trial, this research measures how well the treatment works in an initial, smaller group, offering participants a chance to contribute to important medical advancements.

Will I have to stop taking my current medications?

The trial allows participants to continue taking certain medications like oral 5-aminosalicylic acid, oral corticosteroids, azathioprine, mercaptopurine, or methotrexate, as long as the doses have been stable for a specified period before joining the study. However, other non-biologic medications for inflammatory bowel disease and certain biologic treatments must be stopped before participating.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that BI 706321 is safe and well-tolerated for people with moderate to severe Crohn's disease. Patients have responded well to the treatment, with no major safety concerns reported.

Ustekinumab, used for a longer time and approved for treating Crohn's disease, has demonstrated safety in long-term studies, with no significant safety issues compared to a placebo.

Overall, both treatments appear safe for people with Crohn's disease based on past studies and current use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Crohn's disease?

Unlike the standard options for Crohn's Disease, which primarily focus on controlling inflammation with biologics like infliximab or adalimumab, BI 706321 is unique because it is a small molecule that can be taken orally. This oral administration could offer a more convenient alternative to the injectable biologics currently in use. Additionally, BI 706321 works in conjunction with ustekinumab, another biologic, potentially enhancing the effectiveness of the treatment for those with moderate to severe Crohn's Disease. Researchers are excited about this combination because it might offer improved outcomes with fewer side effects, providing a new hope for patients who need more effective management of their condition.

What evidence suggests that this trial's treatments could be effective for Crohn's disease?

Research shows that ustekinumab effectively treats moderate to severe Crohn's disease. One study found that 26% of patients using ustekinumab experienced a significant improvement, with bowel inflammation reduced by at least half. In this trial, one group of participants will receive BI 706321 combined with ustekinumab to test their combined effectiveness. Early results suggest that this combination might provide extra benefits, but further research is needed to confirm this. Researchers are carefully studying this combination to determine if it can help people with Crohn's disease achieve even better results. Another group will receive a placebo alongside ustekinumab to compare outcomes. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

Adults aged 18-75 with moderate to severe Crohn's disease can join this trial. They must have a confirmed diagnosis for at least 3 months, active symptoms, and certain inflammation markers. Stable doses of specific medications are required, and women must use effective birth control. Exclusions include recent surgeries, other IBD diagnoses, untreated abscesses or infections like HIV or COVID-19.

Inclusion Criteria

I have tried at least one TNF blocker for Crohn's disease but stopped for some reason.

I have been on a stable dose of oral 5-ASA for at least 4 weeks.

I am on a stable dose of oral corticosteroids for my condition, not exceeding the specified limits.

Exclusion Criteria

I have complications from Crohn's disease that might need surgery or affect treatment assessment.

I haven't taken non-biologic IBD meds like tacrolimus in the last 30 days.

My heart's electrical activity (QT interval) is longer than normal.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BI 706321 or placebo in combination with ustekinumab for 3 months

12 weeks

6 visits (in-person)

Maintenance

Participants receive only ustekinumab for an additional 9 months

36 weeks

7 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BI 706321
• Placebo
• Ustekinumab

Trial Overview The study tests if BI 706321 combined with ustekinumab is beneficial for Crohn's disease treatment compared to ustekinumab alone. Participants will take BI 706321 or placebo tablets daily plus an initial infusion followed by injections of ustekinumab every two months over a year.

How Is the Trial Designed?

Group I: BI 706321 and ustekinumab Experimental Treatment 2 Interventions

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.

Group II: Placebo and ustekinumab Placebo Group 2 Interventions

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.

Who Is Running the Clinical Trial?

Boehringer Ingelheim

Lead Sponsor

Trials

2,566

Recruited

16,150,000+

Published Research Related to This Trial

A study involving 117 Crohn's disease patients, including 39 elderly (≥65 years) and 78 nonelderly (<65 years), found that ustekinumab (UST) is safe and effective for treating elderly patients, with nearly 90% experiencing a clinical response.

Elderly patients were less likely to achieve complete clinical remission compared to nonelderly patients (28.2% vs. 52.6%), but there were no significant differences in adverse events or complications between the two age groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Effectiveness and Safety of Ustekinumab in Elderly Crohn's Disease Patients. Garg, R., Aggarwal, M., Butler, R., et al.[2023]

In a study of 463 Crohn's disease patients treated with ustekinumab for at least 6 months, 56% achieved remission and 70% had a positive response by week 16, demonstrating its effectiveness in real-world settings.

Ustekinumab was found to be safe for long-term use, with an 18% discontinuation rate per patient-year and only 8.4% of patients reporting adverse events, indicating a favorable safety profile in a refractory patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Real-World Effectiveness and Safety of Ustekinumab in Crohn's Disease Patients: The SUSTAIN Study. Chaparro, M., Baston-Rey, I., Fernández-Salgado, E., et al.[2022]

Ustekinumab (STELARA) is a safe and effective treatment for skin conditions related to inflammatory bowel diseases (IBD), including metastatic Crohn's disease and pyoderma gangrenosum, based on a review of 22 articles.

It also effectively addresses paradoxical skin reactions caused by TNF-α inhibitors, such as psoriasis, particularly when these reactions do not improve with standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ustekinumab for the treatment of paradoxical skin reactions and cutaneous manifestations of inflammatory bowel diseases. Wu, J., Smogorzewski, J.[2021]

Ustekinumab (STELARA) is effective for treating moderate-to-severe plaque psoriasis in pediatric patients aged 6 to 12, as shown by a phase III study that developed a pharmacokinetic model to predict its behavior in this age group.

The study successfully used data from adult patients to create a model that predicts clinical responses in children, indicating that ustekinumab's efficacy and safety profile can be extrapolated from adults to younger patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extrapolating Pharmacodynamic Effects From Adults to Pediatrics: A Case Study of Ustekinumab in Pediatric Patients With Moderate to Severe Plaque Psoriasis. Zhou, W., Hu, C., Zhu, Y., et al.[2021]

In a study of 86 Crohn's disease patients who were mostly resistant to other treatments, ustekinumab showed a clinical remission rate of 39.5% after 24 weeks, indicating its effectiveness in managing symptoms.

However, the study found low rates of endoscopic response (20.5%) and remission (7.1%), suggesting that higher doses of ustekinumab may be necessary to improve these endoscopic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ustekinumab Exposure-outcome Analysis in Crohn's Disease Only in Part Explains Limited Endoscopic Remission Rates. Verstockt, B., Dreesen, E., Noman, M., et al.[2020]

In a study of 36 adults with Crohn's disease, 61% responded to ustekinumab treatment after one year, but no distinct gene expression signature was found to predict response, indicating that more research is needed to identify reliable biomarkers.

Among nonresponders, an increased inflammatory response was observed, with 68 genes linked to cytokine activity and chemokine receptor binding, suggesting that these pathways may play a role in treatment resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baseline peripheral blood mononuclear cell (PBMC) transcriptomics before ustekinumab treatment is linked with Crohn Disease clinical response at 1 year. Granot, M., Braun, T., Efroni, G., et al.[2023]

Ustekinumab is an effective treatment for adults with moderately to severely active Crohn's disease who have not responded to or are intolerant of other therapies, showing improved clinical response and remission rates in pivotal phase III trials.

The drug has a unique mechanism of action targeting IL-12 and IL-23 cytokines, and it is generally well tolerated, with serious side effects like infections and malignancies being rare.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ustekinumab: A Review in Moderate to Severe Crohn's Disease. Lamb, YN., Duggan, ST.[2018]

Citations

1. crohnscolitisfoundation.org crohnscolitisfoundation.org/a-study-to-test-whether-bi-706321-combined-with-ustekinumab-helps-people-with-crohns-disease

A study to test whether BI 706321 combined with ... The purpose of this study is to find out whether BI 706321 combined with ustekinumab helps people with Crohn's disease.

2. clinicaltrials.eu clinicaltrials.eu/trial/study-on-bi-706321-and-ustekinumab-for-patients-with-moderate-to-severe-crohns-disease/

Study on BI 706321 and Ustekinumab for Patients with ... This study evaluates the safety and effectiveness of the combination of BI 706321 and ustekinumab for the treatment of moderate to severe Crohn's Disease.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11858795/

Drug Development in Inflammatory Bowel Diseases By the end of the induction period, 26% of patients achieved an endoscopic response (defined as a ≥50% improvement in the SES-CD score), while 49.1% achieved ...

4. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/93/NCT04978493/Prot_002.pdf

Boehringer ~1lll1v lngelheim signal of efficacy, safety and tolerability of BI 706321 in combination with ustekinumab treatment in patients with moderately to severely active CD. This ...

5. clinicaltrialsregister.eu clinicaltrialsregister.eu/ctr-search/trial/2020-004527-16/DK

Clinical Trials Register A study to test whether BI 706321 combined with ustekinumab helps people with Crohn's Disease. A.4.1, Sponsor's protocol code number, 1425-0003.

6. onderzoekmetmensen.nl onderzoekmetmensen.nl/en/node/53423/pdf

A Phase IIa, randomised, double-blind, placebo-controlled ... Keyword: BI 706321, Crohn's Disease, Ustekinumab. Outcome measures ... BI 706321 was safe and well tolerated in patients with moderate to severe ...