BI 706321 + Ustekinumab for Crohn's Disease

Recruiting at 80 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

49 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is for adults with moderate to severe Crohn's disease. It tests if a new medicine, BI 706321, combined with ustekinumab, can help reduce symptoms. Participants take daily pills and receive regular injections, and their health is closely monitored. Ustekinumab is approved for the treatment of Crohn's disease and ulcerative colitis.

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 the combination of BI 706321 and Ustekinumab safe for humans?

Ustekinumab (Stelara) is generally well tolerated in treating Crohn's disease, with serious infections and cancers being rare. It is considered a safe option for patients who have not responded to other treatments, but specific safety data for the combination with BI 706321 is not available. ^{1 2 3 4 5}

What makes the drug combination BI 706321 and Ustekinumab unique for treating Crohn's Disease?

The combination of BI 706321 and Ustekinumab is unique because it pairs a new investigational drug (BI 706321) with Ustekinumab, which is already known for its distinct mechanism of targeting specific proteins (IL-12 and IL-23) involved in inflammation, offering a novel approach for patients who have not responded to other treatments. ^{1 2 3 6 7}

What data supports the effectiveness of the drug Ustekinumab for Crohn's Disease?

Research shows that Ustekinumab, a drug used for Crohn's Disease, helped about 50% of patients achieve clinical remission (symptom relief) after one year. It has been effective for those who did not respond to other treatments, offering a promising alternative for managing the disease. ^{1 2 8 9 10}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: BI 706321 + ustekinumab Experimental Treatment 2 Interventions

Group II: Placebo + ustekinumab Placebo Group 2 Interventions

Who Is Running the Clinical Trial?

Boehringer Ingelheim

Lead Sponsor

Trials

2,566

Recruited

16,150,000+

Findings from Research

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]

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 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]

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]

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]

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]

References

1. United States 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. [2023]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Ustekinumab: A Review in Moderate to Severe Crohn's Disease. [2018]

3. United States 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. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Long-Term Real-World Effectiveness and Safety of Ustekinumab in Crohn's Disease Patients: The SUSTAIN Study. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Ustekinumab Exposure-outcome Analysis in Crohn's Disease Only in Part Explains Limited Endoscopic Remission Rates. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Real-World Effectiveness and Safety of Ustekinumab in Elderly Crohn's Disease Patients. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

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

8. United States pubmed.ncbi.nlm.nih.gov

The Real-World Effectiveness and Safety of Ustekinumab in the Treatment of Crohn's Disease: Results From the SUCCESS Consortium. [2023]

9. Spain pubmed.ncbi.nlm.nih.gov

Ustekinumab in Crohn's disease: effectiveness and safety in clinical practice. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Subcutaneous rather than intravenous ustekinumab induction is associated with comparable circulating drug levels and early clinical response: a pilot study. [2019]