Targeted Therapies for Crohn's Disease

(Target CD Trial)

Recruiting at 193 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: AbbVie

Must not be taking: P19 inhibitors

Disqualifiers: Ulcerative colitis, Ostomy, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

Crohn's disease (CD) is a long-lasting disease that causes severe inflammation (redness, swelling), in the digestive tract, most frequently affecting the bowels. It can cause many different symptoms including belly pain, diarrhea, tiredness, and weight loss. Treatments are available but do not work the same for all patients or may stop working over time. This study will evaluate the effectiveness and adverse events of targeted therapies (TaTs) for adult participants with moderate to severe CD. The medicines assessed in this study are risankizumab, ABBV-382 and lutikizumab. When participants join the study, they will be randomized into available study treatment groups. Adult participants with CD will be enrolled. Around 500 participants will be enrolled in the study at approximately 300 sites worldwide. Risankizumab and ABBV-382 are given as an injection under the skin or as an infusion into the vein. Lutikizumab is given as an injection under the skin. Each group includes a 12-week induction period, a 12-week maintenance period, and an optional long-term extension period where medication will be given after the maintenance period. There may be higher treatment burden for participants in this trial compared to their standard of care treatment without participating in this study. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, endoscopies, checking for side effects and completing questionnaires and a daily diary.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, if you are currently on investigational targeted therapies, you may need to stop them at least 30 days before starting the trial, unless your drug levels are undetectable.

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

Research shows that similar drugs like ustekinumab and vedolizumab are effective in treating Crohn's disease, suggesting that targeted therapies can be beneficial for this condition. ^{1 2 3 4 5}

Is Risankizumab safe for humans?

Risankizumab has shown acceptable safety in studies for treating Crohn's disease, with long-term safety being investigated in ongoing research. ^{3 6 7 8 9}

What makes the drug ABBV-382, Lutikizumab, and Risankizumab unique for treating Crohn's disease?

This drug combination is unique because it includes Risankizumab, which targets interleukin-23 (a protein involved in inflammation) and has shown promise in maintaining remission in Crohn's disease, offering a novel mechanism of action compared to traditional treatments. ^{3 7 10 11 12}

Research Team

ABBVIE INC.

Principal Investigator

AbbVie

Eligibility Criteria

Adults with moderate to severe Crohn's Disease who weigh at least 40 kg and have been diagnosed for over 3 months. They must show intolerance or inadequate response to existing targeted therapies, have a certain level of disease activity, and evidence of inflammation in the bowels.

Inclusion Criteria

My weight is at least 40 kg.

My Crohn's disease activity index (CDAI) score is 220 or more.

My bowel inflammation is confirmed by a specific endoscopy score.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Participants receive targeted therapies during the 12-week induction period

12 weeks

Regular visits at a hospital or clinic

Maintenance

Participants continue receiving targeted therapies during the 12-week maintenance period

12 weeks

Regular visits at a hospital or clinic

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term Extension

Participants may opt into continuation of treatment long-term

Up to 72 weeks

Treatment Details

Interventions

• ABBV-382 (Monoclonal Antibodies)
• Lutikizumab (Monoclonal Antibodies)
• Risankizumab (Monoclonal Antibodies)

Trial Overview The trial is testing three drugs: Risankizumab, ABBV-382, and Lutikizumab. Participants will be randomly assigned to one of these treatments and monitored over a period that includes induction (12 weeks), maintenance (12 weeks), and possibly an extension phase.

Participant Groups

Group I: Monotherapy: Risankizumab Experimental Treatment 1 Intervention

Participants will receive Risankizumab Dose A as IV infusion and Risankizumab Dose B as SC injection.

Group II: Monotherapy: Lutikizumab Experimental Treatment 1 Intervention

Participants will receive Lutikizumab Dose A, Dose B and Dose C as SC injection.

Group III: Monotherapy: ABBV-382 Experimental Treatment 1 Intervention

Participants will receive ABBV-382 Dose A as IV infusion and ABBV-382 Dose B as SC injection.

Group IV: Long-Term Extension: Risankizumab Monotherapy Experimental Treatment 1 Intervention

Participants will receive Risankizumab Dose A as IV infusion and/or Risankizumab Dose B as SC injection for up to 72 weeks.

Group V: Combination Therapy: Risankizumab and Lutikizumab Experimental Treatment 2 Interventions

Participants will receive Risankizumab Dose A as IV infusion and Risankizumab Dose C as SC injection; and Lutikizumab Dose A, Dose B and Dose C as SC injection.

Group VI: Combination Therapy: Risankizumab and ABBV-382 Experimental Treatment 2 Interventions

Participants will receive Risankizumab Dose A as IV infusion and Risankizumab Dose C as SC injection; and ABBV-382 Dose A as IV infusion and ABBV-382 Dose B as SC injection.

Who Is Running the Clinical Trial?

AbbVie

Lead Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Findings from Research

In the STARDUST phase 3b trial, ustekinumab demonstrated significant long-term efficacy in treating Crohn's disease, with clinical remission rates reaching 68.4% among patients in the long-term extension after 104 weeks.

The study showed a favorable safety profile with no new safety signals, and the flexible dosing strategy allowed for both escalation and de-escalation of treatment based on patient response, maintaining effective clinical and endoscopic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical trial: Clinical and endoscopic outcomes with ustekinumab in patients with Crohn's disease: Results from the long-term extension period of STARDUST. Peyrin-Biroulet, L., Vermeire, S., D'Haens, G., et al.[2023]

In a long-term safety study involving 2,243 patients with ulcerative colitis (UC) and Crohn's disease (CD), vedolizumab demonstrated a favorable safety profile, with no new safety concerns or unexpected adverse events over an average treatment duration of 42.4 months for UC and 31.5 months for CD.

Vedolizumab maintained clinical response in a significant portion of patients, with 33% of UC patients and 28% of CD patients achieving clinical remission after 400 weeks of treatment, indicating its efficacy for long-term management of these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety of vedolizumab for inflammatory bowel disease. Loftus, EV., Feagan, BG., Panaccione, R., et al.[2021]

In a phase 2b study involving 246 patients with moderately to severely active Crohn's disease, briakinumab did not meet the primary endpoint of clinical remission at week 6, but showed numerically greater rates of remission and response at weeks 6, 12, and 24 compared to placebo.

Briakinumab demonstrated a safety and tolerability profile similar to that of placebo, with comparable rates of serious adverse events and other safety concerns, suggesting it may be a viable treatment option for Crohn's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Briakinumab for treatment of Crohn's disease: results of a randomized trial. Panaccione, R., Sandborn, WJ., Gordon, GL., et al.[2019]

Vedolizumab demonstrated the ability to maintain steroid-free clinical remission in 27.2% of patients with Crohn's disease and 40.5% of patients with ulcerative colitis at week 54, indicating its efficacy in long-term treatment.

The safety profile of vedolizumab was reasonable, with no deaths reported and only 7.2% of patients experiencing severe adverse events, although a notable number of patients, especially those with Crohn's disease, experienced a loss of response during the first year of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

One-year effectiveness and safety of vedolizumab therapy for inflammatory bowel disease: a prospective multicentre cohort study. Amiot, A., Serrero, M., Peyrin-Biroulet, L., et al.[2022]

In a 52-week study involving 24 patients with Crohn's disease who previously lost response to infliximab, adalimumab demonstrated significant efficacy, with clinical remission rates increasing from 35% at baseline to 58% at week 52.

Adalimumab was well tolerated, with no patients experiencing intolerance and no serious toxicities reported, indicating it is a safe option for maintaining remission in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adalimumab maintenance therapy for Crohn's disease with intolerance or lost response to infliximab: an open-label study. Peyrin-Biroulet, L., Laclotte, C., Bigard, MA.[2015]

In a long-term study of 65 patients with moderate-to-severe Crohn's disease, risankizumab was well tolerated over a median of 33 months, with no new safety concerns and a low rate of serious adverse events (24.6 events/100 patient-years).

Efficacy was maintained throughout the study, with over 71% of patients achieving clinical remission and more than 42% achieving endoscopic remission, indicating that risankizumab remains effective for long-term treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Safety and Efficacy of Risankizumab Treatment in Patients with Crohn's Disease: Results from the Phase 2 Open-Label Extension Study. Ferrante, M., Feagan, BG., Panés, J., et al.[2022]

Subcutaneous risankizumab, a selective anti-IL-23 antibody, has been shown to be an effective maintenance therapy for patients with moderately to severely active Crohn's disease, achieving higher rates of clinical remission and endoscopic response compared to placebo in a study involving 542 participants.

The treatment was well tolerated, with adverse event rates similar across all groups, indicating that risankizumab could be a safe new option for patients who need ongoing management of their condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risankizumab as maintenance therapy for moderately to severely active Crohn's disease: results from the multicentre, randomised, double-blind, placebo-controlled, withdrawal phase 3 FORTIFY maintenance trial. Ferrante, M., Panaccione, R., Baert, F., et al.[2022]

Vedolizumab, a gut-selective integrin blocker for Crohn's disease and ulcerative colitis, showed a similar rate of serious adverse events (35.9%) compared to anti-TNF drugs (32.1%) in a study analyzing 499 reports for vedolizumab and 119,620 for anti-TNFs.

The study identified 22 groups of adverse events associated with vedolizumab, including 9 with serious outcomes, suggesting potential cardiovascular risks; however, these findings are preliminary and require further investigation through long-term studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of the real-world safety profile of vedolizumab using the United States Food and Drug Administration adverse event reporting system. Cross, RK., Chiorean, M., Vekeman, F., et al.[2023]

In a systematic review of eight studies involving 1281 Crohn's disease patients who had previously been treated with anti-TNF agents, a second biological therapy was found to be significantly more effective than placebo in inducing remission and response, with odds ratios of 2.2 and 1.9, respectively.

No single biological agent was shown to be superior to others in efficacy, although adalimumab showed relatively better results for inducing remission, highlighting the need for further research to optimize treatment strategies for patients who do not respond to initial therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Review with Network Meta-Analysis: Efficacy of Induction Therapy with a Second Biological Agent in Anti-TNF-Experienced Crohn's Disease Patients. Pagnini, C., Siakavellas, SI., Bamias, G.[2022]

Infliximab and adalimumab are effective in inducing clinical response and maintaining remission in Crohn's disease, while infliximab is also effective for ulcerative colitis, highlighting their role as key therapies for these conditions.

Vedolizumab, an anti-α4β7 integrin antibody, shows a favorable efficacy and safety profile, making it a promising option for treating Crohn's disease, while other monoclonal antibodies like ustekinumab are also being developed to target specific inflammatory pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current directions of biologic therapies in inflammatory bowel disease. Reenaers, C., Louis, E., Belaiche, J.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Clinical trial: Clinical and endoscopic outcomes with ustekinumab in patients with Crohn's disease: Results from the long-term extension period of STARDUST. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Long-term safety of vedolizumab for inflammatory bowel disease. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Briakinumab for treatment of Crohn's disease: results of a randomized trial. [2019]

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

One-year effectiveness and safety of vedolizumab therapy for inflammatory bowel disease: a prospective multicentre cohort study. [2022]

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

Adalimumab maintenance therapy for Crohn's disease with intolerance or lost response to infliximab: an open-label study. [2015]

6. England pubmed.ncbi.nlm.nih.gov

Long-Term Safety and Efficacy of Risankizumab Treatment in Patients with Crohn's Disease: Results from the Phase 2 Open-Label Extension Study. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Risankizumab as maintenance therapy for moderately to severely active Crohn's disease: results from the multicentre, randomised, double-blind, placebo-controlled, withdrawal phase 3 FORTIFY maintenance trial. [2022]

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

Retrospective Analysis of Safety of Vedolizumab in Patients With Inflammatory Bowel Diseases. [2021]

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

Assessment of the real-world safety profile of vedolizumab using the United States Food and Drug Administration adverse event reporting system. [2023]

10. Egypt pubmed.ncbi.nlm.nih.gov

Systematic Review with Network Meta-Analysis: Efficacy of Induction Therapy with a Second Biological Agent in Anti-TNF-Experienced Crohn's Disease Patients. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Natalizumab for induction of remission in Crohn's disease. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Current directions of biologic therapies in inflammatory bowel disease. [2023]