Mirikizumab for Crohn's Disease

(VIVID-2 Trial)

Not currently recruiting at 802 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the long-term effectiveness and safety of the drug mirikizumab for people with Crohn's disease. Participants will receive the drug either intravenously (IV) or subcutaneously (under the skin). It suits individuals who participated in specific previous Crohn's studies and have not developed new health conditions that could pose risks. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment for Crohn's disease.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that mirikizumab, administered either intravenously (IV) or subcutaneously (SC), is generally safe for treating Crohn's disease. The IV form has a safety profile similar to its use in ulcerative colitis, with most patients tolerating it well. Healthcare providers administer the first three doses to monitor for any immediate reactions.

For the SC form, common side effects include mild issues like colds and injection site reactions, which are typical and usually not serious. Notably, the drug does not accumulate in the body over time when given as a monthly injection.

Overall, studies suggest that mirikizumab is safe for individuals with Crohn's disease, as demonstrated in previous research. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Mirikizumab is unique because it specifically targets interleukin-23 (IL-23), a protein that plays a key role in inflammation associated with Crohn's disease. Unlike standard treatments like corticosteroids or anti-TNF therapies, which broadly suppress the immune system, mirikizumab offers a more precise approach, potentially reducing inflammation with fewer side effects. Researchers are also excited about the flexible delivery options of mirikizumab, which can be administered both intravenously and subcutaneously, offering more convenience and possibly improving treatment adherence for patients. These features make mirikizumab a promising contender in the quest for more effective and patient-friendly Crohn’s disease therapies.

What evidence suggests that mirikizumab might be an effective treatment for Crohn's disease?

Research has shown that mirikizumab holds promise for treating Crohn's disease. Studies found that many patients experienced symptom relief, such as reduced stomach pain, within six weeks. More than 90% of those who improved after one year remained well after two years of ongoing treatment. These studies also confirmed that mirikizumab is generally safe and well-tolerated. In this trial, participants will receive either the IV (intravenous) or SC (subcutaneous) form of mirikizumab, both of which appear effective. This information offers hope that mirikizumab could be a reliable long-term option for managing Crohn's disease. ^{6 7 8 9 10}

Who Is on the 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

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: All AMAG Participants: Miri 300 mg SC Experimental Treatment 1 Intervention

Participants from Study AMAG who continued into Study AMAX received mirikizumab 300 mg SC Q4W for 52 weeks.

Group II: AMAM Ustekinumab (Uste): Miri 300 mg SC Experimental Treatment 1 Intervention

Participants assigned to ustekinumab in Study AMAM who achieved Endoscopic Response at Week 52 of AMAM continued into Study AMAX and received mirikizumab 300 mg SC Q4W for 52 weeks.

Group III: AMAM Uste: Miri 900 mg IV Then 300 mg SC Experimental Treatment 1 Intervention

Participants assigned to ustekinumab in Study AMAM who did not achieve Endoscopic Response at Week 52 of AMAM continued into Study AMAX and received mirikizumab 900 mg IV Q4W for 3 doses, followed by mirikizumab 300 mg SC Q4W for 52 weeks.

Group IV: AMAM Placebo (PBO)/Miri: Miri 300 mg SC Experimental Treatment 1 Intervention

Participants assigned to placebo in Study AMAM who switched from placebo to mirikizumab at week 12 and achieved Endoscopic Response at Week 52 of AMAM continued into Study AMAX and received mirikizumab 300 mg SC Q4W for 52 weeks.

Group V: AMAM PBO: Miri 900 mg IV Then 300 mg SC Experimental Treatment 1 Intervention

Participants assigned to placebo in Study AMAM who did not achieve Endoscopic Response at Week 52 of AMAM continued into Study AMAX and received mirikizumab 900 mg IV Q4W for 3 doses, followed by mirikizumab 300 mg SC Q4W for 52 weeks.

Group VI: AMAM PBO: Miri 300 mg SC Experimental Treatment 1 Intervention

Participants assigned to placebo in Study AMAM who achieved Endoscopic Response at Week 52 of AMAM continued into Study AMAX and received mirikizumab 300 mg SC Q4W for 52 weeks.

Group VII: AMAM PBO/Miri: Miri 900 mg IV Then 300 mg SC Experimental Treatment 1 Intervention

Participants assigned to placebo in Study AMAM who switched from placebo to mirikizumab at week 12 and did not achieve Endoscopic Response at Week 52 of AMAM continued into Study AMAX and received mirikizumab 900 mg IV Q4W for 3 doses, followed by mirikizumab 300 mg SC Q4W for 52 weeks.

Group VIII: AMAM Mirikizumab (Miri): Miri 300 mg SC Experimental Treatment 1 Intervention

Participants assigned to mirikizumab in Study AMAM who achieved Endoscopic Response at Week 52 of AMAM continued into Study AMAX and received mirikizumab 300 milligrams (mg) subcutaneously (SC) every 4 weeks (Q4W) for 52 weeks.

Group IX: AMAM Miri: Miri 900 mg IV Then 300 mg SC Experimental Treatment 1 Intervention

Participants assigned to mirikizumab in Study AMAM who did not achieve Endoscopic Response at Week 52 of AMAM continued into Study AMAX and received mirikizumab 900 mg intravenously (IV) Q4W for 3 doses, followed by mirikizumab 300 mg SC Q4W for 52 weeks.

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

Published Research Related to This Trial

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]

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]

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]

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]

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 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]

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]

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]

Citations

1.

omvoh.lilly.com

omvoh.lilly.com/hcp/crohns-disease/clinical-studies

Clinical Studies, Trial Design & Data | CD - Omvoh - Eli Lilly

See Omvoh efficacy data for Crohn's disease, including remission data through 2 years, outcomes for both bio-naïve and bio-failed patients, ...

2.

investor.lilly.com

investor.lilly.com/node/51431/pdf

Lilly reports one-year histologic outcomes in Phase 3 study ...

VIVID-1 was a Phase 3, randomized, double-blind, treat-through study that evaluated the safety and efficacy of mirikizumab compared with placebo.

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03926130

NCT03926130 | A Study of Mirikizumab (LY3074828) in ...

The reason for this study is to see if the study drug mirikizumab is safe and effective in participants with moderately to severely active Crohn's disease.

4.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39581202/

Efficacy and safety of mirikizumab in patients with ...

The safety of mirikizumab in Crohn's disease was consistent with its known favourable profile. Interpretation: Mirikizumab was safe and ...

5.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02891226

NCT02891226 | A Study of Mirikizumab (LY3074828) in ...

The purpose of this study is to evaluate the safety and effectiveness of the study drug Mirikizumab in participants with active Crohn's Disease. Official ...

6.

omvoh.lilly.com

omvoh.lilly.com/hcp/safety-profile

Safety Profile & Adverse Events | Omvoh® (mirikizumab-mrkz)

Overall, the safety profiles in adult patients with CD and in adult patients with UC treated with Omvoh are generally consistent.

7.

omvoh.lilly.com

omvoh.lilly.com/crohns/clinical-results

Crohn's Disease Clinical Results & Safety Data - Omvoh

You will receive your first 3 doses of Omvoh through a vein in your arm (intravenous infusion) in a healthcare facility by a healthcare provider every 4 weeks.

8.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2025/761279s003lbl.pdf

highlights of prescribing information - accessdata.fda.gov

OMVOH for intravenous infusion for ulcerative colitis and Crohn's disease. OMVOH (mirikizumab-mrkz) injection is a sterile, preservative-free, clear to ...

9.

mayoclinic.org

mayoclinic.org/drugs-supplements/mirikizumab-mrkz-intravenous-route-subcutaneous-route/description/drg-20559672

Mirikizumab-mrkz (intravenous route, subcutaneous route)

For Crohn's disease: Adults—The first 3 doses are given by a doctor through an IV catheter placed in one of your veins at Week 0, Week 4, ...

10.

ema.europa.eu

ema.europa.eu/en/documents/product-information/omvoh-epar-product-information_en.pdf

Omvoh, INN: mirikizumab - EMA

(900 mg every 4 weeks administered by intravenous infusion) in patients with Crohn's disease were. 332 µg/mL (20.6 %) and 1820 µg*day/mL (38.1 %), respectively.