Mirikizumab for Crohn's Disease

(VIVID-2 Trial)

Recruiting at 714 trial locations

Overseen By Ziad Younes

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Eli Lilly and Company

Disqualifiers: Cancer, Important infections, Hypersensitivity, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

778 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing mirikizumab to see if it can help people with Crohn's disease feel better over a long time and ensure it is safe. The drug works by reducing gut inflammation.

Do I have to stop taking my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more details.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the idea that Mirikizumab for Crohn's Disease is an effective treatment?

The available research does not provide any data on Mirikizumab for Crohn's Disease. Instead, it focuses on other treatments for different conditions, such as colorectal cancer and gastric cancer. Therefore, there is no information here to support the effectiveness of Mirikizumab for Crohn's Disease. ^{1 2 3 4 5}

What safety data exists for Mirikizumab in treating Crohn's Disease?

The safety of Mirikizumab for Crohn's Disease has been evaluated in a randomized Phase 2 study, which investigated its safety and efficacy in patients with moderate-to-severe Crohn's Disease. Additionally, Mirikizumab has been studied in Phase II and III trials for ulcerative colitis, which may provide relevant safety data due to the similar nature of these conditions. However, specific safety data for Crohn's Disease from these studies is not detailed in the provided abstracts. ^{6 7 8 9 10}

Is Mirikizumab safe for humans?

Mirikizumab has been studied for safety in conditions like Crohn's disease and ulcerative colitis, showing it is generally safe for humans. It has been approved in Japan and received a positive opinion in the EU for treating ulcerative colitis, indicating its safety profile is acceptable for these conditions. ^{6 7 8 9 11}

Is the drug Mirikizumab a promising treatment for Crohn's Disease?

Yes, Mirikizumab is a promising drug for Crohn's Disease. It has shown effectiveness in treating similar conditions like psoriasis and ulcerative colitis. It has been approved in Japan for ulcerative colitis, indicating its potential for Crohn's Disease as well. ^{6 7 8 12 13}

How is the drug Mirikizumab different from other treatments for Crohn's disease?

Mirikizumab is unique because it is a monoclonal antibody that specifically targets interleukin 23p19, a protein involved in inflammation, and it has shown effectiveness in other conditions like psoriasis and ulcerative colitis. It is the first IL-23p19 inhibitor approved for ulcerative colitis, which may offer a new approach for patients with Crohn's disease who do not respond well to conventional therapies. ^{6 7 8 12 13}

Research Team

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM -5 PM Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Eligibility Criteria

This trial is for people who have Crohn's disease and completed previous studies (NCT02891226 or NCT03926130). Women must follow contraception rules. People with new risks like cancer, known allergies to mirikizumab, severe reactions in past trials, pregnancy, certain infections like hepatitis or HIV/AIDS can't join.

Inclusion Criteria

Participants must have completed study I6T-MC-AMAG (NCT02891226) or study I6T-MC-AMAM (NCT03926130)

I am following the required birth control measures.

Exclusion Criteria

I do not have significant infections like hepatitis B/C, HIV/AIDS, or active TB.

I am not allergic to mirikizumab or similar medications.

Participants with a history of active TB with documentation of treatment by the Centers for Disease Control (CDC) and/or World Health Organization (WHO) criteria prior to the originator study are not excluded from the study

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive mirikizumab intravenously (IV) and subcutaneously (SC) to evaluate long-term efficacy and safety

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants continue to receive mirikizumab to assess long-term outcomes

Long-term

Treatment Details

Interventions

• Mirikizumab

Trial Overview The study tests the long-term effects and safety of a drug called Mirikizumab on individuals with Crohn's disease. It aims to see how well it works over an extended period following earlier trials.

Participant Groups

Group I: Mirikizumab SC Experimental Treatment 1 Intervention

Mirikizumab given subcutaneously (SC).

Group II: Mirikizumab IV and SC Experimental Treatment 1 Intervention

Mirikizumab given intravenously (IV) and SC.

Mirikizumab is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Omvoh for:

• Moderately to severely active ulcerative colitis

Approved in United States as Omvoh for:

• Moderately to severely active ulcerative colitis

Approved in Canada as Omvoh for:

• Moderately to severely active ulcerative colitis

Approved in Japan as Omvoh for:

• Moderately to severely active ulcerative colitis

Who Is Running the Clinical Trial?

Eli Lilly and Company

Lead Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Findings from Research

The combination of tivozanib and everolimus was well tolerated in a phase II study, achieving a 50% rate of stable disease in patients with refractory, metastatic colorectal cancer, indicating its potential efficacy.

Patients who experienced grade 1+ hypertension while on treatment had significantly better outcomes, with higher rates of stable disease (65.2%) and longer overall survival (10.6 months), suggesting that hypertension may be a positive response indicator.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter phase II study of tivozanib (AV-951) and everolimus (RAD001) for patients with refractory, metastatic colorectal cancer. Wolpin, BM., Ng, K., Zhu, AX., et al.[2021]

In a phase II trial involving treatment-naïve patients with metastatic colorectal cancer, tivozanib combined with mFOLFOX6 showed comparable progression-free survival (PFS) to bevacizumab with mFOLFOX6, but did not demonstrate superior efficacy, leading to the study's discontinuation.

The safety profile of tivozanib/mFOLFOX6 was tolerable and similar to that of bevacizumab/mFOLFOX6, with adverse events consistent with previous studies, while low levels of neuropilin-1 (NRP-1) may indicate a potential predictive biomarker for tivozanib's effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BATON-CRC: A Phase II Randomized Trial Comparing Tivozanib Plus mFOLFOX6 with Bevacizumab Plus mFOLFOX6 in Stage IV Metastatic Colorectal Cancer. Benson, AB., Kiss, I., Bridgewater, J., et al.[2018]

In a study involving 256 matched patients (128 receiving fruquintinib and 128 receiving other TKIs), fruquintinib significantly increased median progression-free survival (PFS) to 3.71 months compared to 2.49 months for other TKIs, indicating its efficacy as a third-line treatment for metastatic colorectal cancer (mCRC).

Subgroup analyses revealed that fruquintinib provided notable PFS benefits for patients with specific characteristics, such as those who had undergone two or three prior chemotherapy regimens and those with rectal or left-sided tumors, suggesting that it may be particularly effective for certain patient profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multi-center effectiveness comparison study of fruquintinib with constructed external control cohort of other targeted kinase inhibitors using real-world data in third-line treatment of metastatic colorectal cancer. Jin, Y., Li, J., Shen, L., et al.[2022]

In a 4-week randomized trial involving 396 renal transplant recipients, switching from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPS) showed a trend towards improved gastrointestinal (GI) symptoms, with 62% of EC-MPS patients meeting the primary efficacy outcome compared to 55% of MMF patients, although this difference was not statistically significant.

EC-MPS was particularly effective in reducing indigestion symptoms and showed significant benefits in specific subgroups, including patients with diabetes and those on steroids, suggesting that EC-MPS may be a better option for certain patients experiencing GI issues post-transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enteric-coated mycophenolate sodium versus mycophenolate mofetil in renal transplant recipients experiencing gastrointestinal intolerance: a multicenter, double-blind, randomized study. Langone, AJ., Chan, L., Bolin, P., et al.[2022]

In the Phase III REGARD trial, ramucirumab, a monoclonal antibody targeting VEGFR2, improved median overall survival in patients with refractory metastatic gastric cancer to 5.2 months compared to 3.8 months for placebo, indicating its efficacy as a treatment option.

The study highlights the need for multi-target approaches to angiogenesis and predictive biomarkers to enhance patient selection for anti-angiogenic therapies, suggesting ongoing research in optimizing treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted inhibition of VEGF receptor 2: an update on ramucirumab. Clarke, JM., Hurwitz, HI.[2023]

In a study of 191 patients with moderate-to-severe Crohn's disease, mirikizumab significantly improved endoscopic response at Week 12 compared to placebo, with the highest response rate observed in the 1000 mg group (43.8%).

Mirikizumab demonstrated durable efficacy, maintaining a high endoscopic response rate of around 58.5% at Week 52, while the safety profile was comparable to placebo, indicating it is a promising treatment option for Crohn's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Mirikizumab in a Randomized Phase 2 Study of Patients With Crohn's Disease. Sands, BE., Peyrin-Biroulet, L., Kierkus, J., et al.[2022]

Mirikizumab, an anti-IL-23p19 monoclonal antibody, was approved in March 2023 in Japan for treating moderate to severe ulcerative colitis, marking it as the first IL-23p19 inhibitor approved for this condition.

In the EU, mirikizumab received a positive opinion for adult patients with active ulcerative colitis who did not respond to conventional or biologic therapies, highlighting its potential as a new treatment option for difficult-to-treat cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mirikizumab: First Approval. Keam, SJ.[2023]

Mirikizumab, an anti-interleukin-23 monoclonal antibody, demonstrated pharmacokinetic properties typical of monoclonal antibodies, with a half-life of approximately 9.5 days and a subcutaneous bioavailability of 48%, based on data from 1362 patients with ulcerative colitis.

The study found that while body weight and serum albumin levels influenced the drug's clearance and distribution, these effects were relatively small compared to individual variability, suggesting that no dose adjustments are necessary based on patient characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mirikizumab Pharmacokinetics in Patients with Moderately to Severely Active Ulcerative Colitis: Results from Phase III LUCENT Studies. Chua, L., Friedrich, S., Zhang, XC.[2023]

In phase 3 studies (LUCENT-1 and LUCENT-2) involving 1162 patients with moderately-to-severely active ulcerative colitis, mirikizumab significantly improved quality of life outcomes, including scores on the Inflammatory Bowel Disease Questionnaire and the 36-Item Short Form Health Survey.

Mirikizumab-treated patients showed higher rates of achieving response and remission in quality of life measures compared to placebo, indicating its efficacy in enhancing overall well-being in patients with ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mirikizumab Improves Quality of Life in Patients With Moderately-to-Severely Active Ulcerative Colitis: Results From the Phase 3 LUCENT-1 Induction and LUCENT-2 Maintenance Studies. Sands, BE., Feagan, BG., Hunter Gibble, T., et al.[2023]

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 study of 100 patients with moderate-to-severe Crohn's disease who had previously failed multiple treatments, risankizumab achieved a steroid-free clinical remission rate of 45.8% and a clinical response rate of 78.5% by week 12, indicating its effectiveness in a real-world setting.

The treatment was generally well-tolerated, with 20 adverse events reported, including 7 serious cases, but the majority of patients experienced significant improvements in their condition, highlighting risankizumab's potential as a viable option for refractory Crohn's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of risankizumab induction therapy for 100 patients with Crohn's disease: A GETAID multicentre cohort study. Fumery, M., Defrance, A., Roblin, X., et al.[2023]

Risankizumab-rzaa, a selective IL-23 inhibitor, has been shown to significantly improve clinical remission and endoscopic response in patients with moderate to severe Crohn's disease, based on results from three phase 3 studies involving multiple patients.

The safety profile of risankizumab-rzaa is comparable to other advanced therapies for Crohn's disease, with common side effects including nasopharyngitis and abdominal pain, making it a viable treatment option for patients who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risankizumab-rzaa: A New Therapeutic Option for the Treatment of Crohn's Disease. Choi, D., Sheridan, H., Bhat, S.[2023]

In a study of 170 participants with Crohn's disease, mirikizumab treatment led to significantly higher rates of histologic response (66% vs 27%) and remission (26% vs 6%) at 12 weeks compared to placebo, indicating its efficacy in promoting mucosal healing.

The study found that early histologic and endoscopic responses were associated with better long-term outcomes, as participants who showed combined responses at week 12 had a higher rate of endoscopic remission at one year (45% vs 4% for those with no response).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Mirikizumab on Histologic Resolution of Crohn's Disease in a Randomized Controlled Phase 2 Trial. Magro, F., Protic, M., De Hertogh, G., et al.[2023]

References

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

Multicenter phase II study of tivozanib (AV-951) and everolimus (RAD001) for patients with refractory, metastatic colorectal cancer. [2021]

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

BATON-CRC: A Phase II Randomized Trial Comparing Tivozanib Plus mFOLFOX6 with Bevacizumab Plus mFOLFOX6 in Stage IV Metastatic Colorectal Cancer. [2018]

3. Switzerland pubmed.ncbi.nlm.nih.gov

A multi-center effectiveness comparison study of fruquintinib with constructed external control cohort of other targeted kinase inhibitors using real-world data in third-line treatment of metastatic colorectal cancer. [2022]

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

Enteric-coated mycophenolate sodium versus mycophenolate mofetil in renal transplant recipients experiencing gastrointestinal intolerance: a multicenter, double-blind, randomized study. [2022]

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

Targeted inhibition of VEGF receptor 2: an update on ramucirumab. [2023]

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

Efficacy and Safety of Mirikizumab in a Randomized Phase 2 Study of Patients With Crohn's Disease. [2022]

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

Mirikizumab: First Approval. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Mirikizumab Pharmacokinetics in Patients with Moderately to Severely Active Ulcerative Colitis: Results from Phase III LUCENT Studies. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Mirikizumab Improves Quality of Life in Patients With Moderately-to-Severely Active Ulcerative Colitis: Results From the Phase 3 LUCENT-1 Induction and LUCENT-2 Maintenance Studies. [2023]

10. 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]

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

Effectiveness and safety of risankizumab induction therapy for 100 patients with Crohn's disease: A GETAID multicentre cohort study. [2023]

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

Risankizumab-rzaa: A New Therapeutic Option for the Treatment of Crohn's Disease. [2023]

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

Effects of Mirikizumab on Histologic Resolution of Crohn's Disease in a Randomized Controlled Phase 2 Trial. [2023]