Vedolizumab for Ulcerative Colitis and Crohn's Disease

(PANORAMA Trial)

Recruiting at 3 trial locations

Overseen By Takeda Contact

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Takeda

Must not be taking: Anti-integrin antibodies

Disqualifiers: Active infection, Ileostomy, Malignancy, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 50 weeks

400 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Ulcerative Colitis (UC) and Crohn's Disease (CD) are long-term conditions in the gut that can cause diarrhea, swelling (inflammation), bleeding from the anus, and belly pain. The main aim of this study is to check for how many participants with UC and CD signs and symptoms disappear after 3.5 months (14 weeks) of treatment with Vedolizumab (this is called remission). Participants will be treated with Vedolizumab for approximately 1 year (50 weeks). During the first 1.5 months (6 weeks), participants will receive Vedolizumab as an infusion in the vein (called intravenously). After this, participants will receive Vedolizumab as an injection under the skin (called subcutaneously) for the rest of the treatment. Participants for whom the treatment does not seem to work well after 3.5 months (14 weeks) will stop treatment with Vedolizumab and can change to another treatment and also there will be additional required visits at 6 months (26 weeks) and at 1 year (52 weeks). All participants will be checked again 4.5 months (18 weeks) after their last treatment with Vedolizumab. During the study, participants will visit their study clinic several times.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you cannot use corticosteroid enemas or suppositories within 2 weeks before screening, and you should not have received certain advanced treatments recently. It's best to discuss your current medications with the trial team.

Is vedolizumab safe for humans?

Vedolizumab has been shown to be generally safe for people with ulcerative colitis and Crohn's disease, with studies noting its safety in both short-term and long-term use. ^{1 2 3 4 5}

How is the drug vedolizumab different from other treatments for ulcerative colitis and Crohn's disease?

Vedolizumab is unique because it is a gut-selective anti-lymphocyte trafficking agent, meaning it specifically targets the gut to reduce inflammation without affecting the rest of the body. This makes it different from other treatments that may have broader effects on the immune system. ^{3 6 7 8 9}

What data supports the effectiveness of the drug Vedolizumab for treating ulcerative colitis and Crohn's disease?

Vedolizumab has shown effectiveness in treating ulcerative colitis and Crohn's disease, with studies indicating that higher levels of the drug in the body are linked to remission without the need for corticosteroids (a type of medication that reduces inflammation). Long-term studies and real-world data also support its use, showing it can help manage these conditions over time. ^{6 10 11 12 13}

Who Is on the Research Team?

Study Director

Principal Investigator

Takeda

Are You a Good Fit for This Trial?

Adults aged 18-80 with Ulcerative Colitis or Crohn's Disease can join this trial. They must be up-to-date on immunizations, understand the study requirements, and agree to use effective contraception. Pregnant women, breastfeeding mothers, and those planning to donate sperm or ova during the study and for 18 weeks after cannot participate.

Inclusion Criteria

I have signed the consent form and any privacy documents for the study.

I agree not to donate eggs during and for 18 weeks after the study.

I understand and can follow the study's requirements.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Vedolizumab intravenously for the first 6 weeks, followed by subcutaneous injections every 2 weeks until Week 50

50 weeks

Several visits throughout the treatment period

Follow-up

Participants are monitored for safety and effectiveness after treatment

18 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Vedolizumab

Trial Overview The trial is testing Vedolizumab's ability to induce remission in UC and CD patients over a year. Initially given intravenously for six weeks, then as a subcutaneous injection until week 50. Effectiveness is assessed at week 14; non-responders switch treatments.

How Is the Trial Designed?

Group I: UC Participants: Vedolizumab Experimental Treatment 2 Interventions

Participants with moderate to severely active UC will receive vedolizumab 300 milligrams (mg), intravenous (IV) infusion at Weeks 0 and 2. Following the first 2 vedolizumab IV doses, participant may be switched to vedolizumab 108 mg subcutaneous (SC) injection at Week 6, to be administered every 2 weeks until Week 50. Treating health care practitioner (HCP) may give an additional dose of vedolizumab IV at Week 6 with mandatory transition by Week 14.

Group II: CD Participants: Vedolizumab Experimental Treatment 2 Interventions

Participants with moderate to severely active CD will receive vedolizumab 300 mg, IV infusion at Weeks 0 and 2. Following the first 2 vedolizumab IV doses, participant may be switched to vedolizumab 108 mg SC injection at Week 6, to be administered every 2 weeks until Week 50. Treating HCP may give an additional dose of vedolizumab IV at Week 6 with mandatory transition by Week 14.

Who Is Running the Clinical Trial?

Takeda

Lead Sponsor

Trials

1,255

Recruited

4,219,000+

Dr. Naoyoshi Hirota

Takeda

Chief Medical Officer since 2020

MD from University of Tokyo

Christophe Weber

Takeda

Chief Executive Officer since 2015

PhD in Molecular Biology from Université de Montpellier

Published Research Related to This Trial

In a study of 53 patients with ulcerative colitis and Crohn's disease receiving vedolizumab therapy, 20% of ulcerative colitis patients and 14.3% of Crohn's disease patients achieved remission by week 30, indicating some efficacy in a treatment-refractory population.

Despite some patients responding to vedolizumab, a significant portion (48% for ulcerative colitis and 39.4% for Crohn's disease) did not respond satisfactorily, highlighting the need for alternative treatment options for those not achieving remission.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Outcomes of Vedolizumab Therapy in Ulcerative Colitis and Crohn's Disease at a Tertiary Referral Center. Hoffmann, P., Krisam, J., Stremmel, W., et al.[2018]

In a study of 258 inflammatory bowel disease patients on maintenance vedolizumab, those in clinical and biochemical remission had significantly higher drug concentrations (12.7 µg/mL) compared to those with active disease (10.1 µg/mL), indicating a strong association between higher vedolizumab levels and remission.

Patients with vedolizumab concentrations above 11.5 µg/mL were nearly 2.4 times more likely to achieve corticosteroid-free clinical and biochemical remission, suggesting that maintaining adequate drug levels is crucial for effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Higher Trough Vedolizumab Concentrations During Maintenance Therapy are Associated With Corticosteroid-Free Remission in Inflammatory Bowel Disease. Ungaro, RC., Yarur, A., Jossen, J., et al.[2020]

In a long-term study involving 72 patients with ulcerative colitis (UC) and Crohn's disease (CD), vedolizumab demonstrated significant clinical efficacy, with 39% of patients achieving a clinical response and 58.3% achieving clinical remission after treatment.

Vedolizumab was well-tolerated over the treatment period of up to 78 weeks, with no deaths or serious infections reported, indicating a favorable safety profile similar to previous studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term clinical experience with vedolizumab in patients with inflammatory bowel disease. Parikh, A., Fox, I., Leach, T., et al.[2022]

In a real-world study of 132 patients with moderate to severe Crohn's disease (CD) and ulcerative colitis (UC), vedolizumab showed sustained clinical response, with 35% of UC patients and 31% of CD patients achieving steroid-free remission after 12 months.

Mucosal healing was observed in 52% of UC patients and 30% of CD patients, indicating that vedolizumab is effective in promoting healing in the intestines, with most adverse events being minor and 74% of patients continuing treatment after one year.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vedolizumab as Induction and Maintenance for Inflammatory Bowel Disease: 12-month Effectiveness and Safety. Christensen, B., Colman, RJ., Micic, D., et al.[2020]

In a study of 1087 patients with Crohn's disease and ulcerative colitis, vedolizumab demonstrated a favorable safety profile, with a low overall infection rate of 6.3% and non-infectious adverse events primarily being arthralgias (2.9%).

Factors such as active smoking and the use of multiple immunosuppressive agents were found to significantly increase the risk of infections in patients receiving vedolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective Analysis of Safety of Vedolizumab in Patients With Inflammatory Bowel Diseases. Meserve, J., Aniwan, S., Koliani-Pace, JL., et al.[2021]

Vedolizumab has been shown to be effective in managing ulcerative colitis, providing significant improvements in patient symptoms and disease control.

The review also highlights that vedolizumab has a favorable safety profile, making it a suitable treatment option for patients with ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of vedolizumab for the treatment of ulcerative colitis. Lau, MS., Tsai, HH.[2020]

Vedolizumab is an effective treatment for moderate to severe ulcerative colitis (UC) and Crohn's disease (CD), helping to induce and maintain clinical response and remission, as shown in multiple phase trials.

The drug is generally well tolerated, with common side effects including nasopharyngitis and headache, but it has not been linked to serious conditions like progressive multifocal leukoencephalopathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vedolizumab: an α4β7 integrin inhibitor for inflammatory bowel diseases. Smith, MA., Mohammad, RA.[2018]

In a study involving 311 patients with ulcerative colitis (UC) and Crohn's disease (CD), vedolizumab demonstrated high treatment persistence, with 93.9% of UC patients and 91.6% of CD patients remaining on a reduced dosing schedule of every 8 weeks after 2 years.

The safety profile of vedolizumab remained consistent with previous studies, showing infrequent adverse events and low relapse rates of 9.1% for UC and 14.0% for CD among those who reduced their dosing frequency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vedolizumab treatment persistence and safety in a 2-year data analysis of an extended access programme. Danese, S., Subramaniam, K., Van Zyl, J., et al.[2022]

Vedolizumab demonstrated significant efficacy in bio-naïve patients with ulcerative colitis (UC) and Crohn's disease (CD), with 63.9% of UC patients and 61.7% of CD patients achieving clinical remission by week 52.

Bio-naïve patients with UC experienced a lower risk of serious adverse events compared to those previously treated, indicating a favorable safety profile for vedolizumab in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vedolizumab as the first line of biologic therapy for ulcerative colitis and Crohn's disease - a systematic review with meta-analysis. Attauabi, M., Madsen, GR., Bendtsen, F., et al.[2023]

In a systematic review of 10 real-world studies involving 395 patients with inflammatory bowel disease (IBD), approximately 50% achieved a clinical response after escalating vedolizumab maintenance dosing from every 8 weeks to every 4 weeks.

Clinical response rates varied between 40% to 73% across the studies, indicating that dose escalation can be an effective strategy for patients experiencing secondary loss of response or non-response to vedolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Effectiveness of Vedolizumab Dose Escalation in Patients With Inflammatory Bowel Disease: A Systematic Literature Review. Patel, D., Martin, S., Luo, M., et al.[2023]

Vedolizumab is an effective treatment option for patients with moderately to severely active Crohn's disease and ulcerative colitis who have not responded to conventional therapies or anti-TNF treatments.

The article provides practical management insights for using vedolizumab, drawing from both published research and the authors' clinical experiences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Questions and answers about the management of Crohn's disease and ulcerative colitis with vedolizumab. Hinojosa Del Val, J., Barreiro-de Acosta, M.[2020]

In a study of 100 patients with moderate to severe ulcerative colitis, vedolizumab demonstrated effectiveness with a clinical response in 62% and clinical remission in 50% after 54 weeks of treatment, indicating it is a viable option for managing this condition.

Despite its effectiveness, 37% of patients who responded to treatment experienced a relapse within 26 weeks after discontinuation, highlighting the need for ongoing monitoring and potential additional therapies after stopping vedolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world outcomes of 54-week vedolizumab therapy and response durability after treatment discontinuation in ulcerative colitis: results from a multicenter prospective POLONEZ study. Eder, P., Kłopocka, M., Cichoż-Lach, H., et al.[2023]

Citations

1. Switzerland pubmed.ncbi.nlm.nih.gov

Real-World Outcomes of Vedolizumab Therapy in Ulcerative Colitis and Crohn's Disease at a Tertiary Referral Center. [2018]

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

Higher Trough Vedolizumab Concentrations During Maintenance Therapy are Associated With Corticosteroid-Free Remission in Inflammatory Bowel Disease. [2020]

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

Long-term clinical experience with vedolizumab in patients with inflammatory bowel disease. [2022]

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

Vedolizumab as Induction and Maintenance for Inflammatory Bowel Disease: 12-month Effectiveness and Safety. [2020]

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

Predictors of Clinical Response and Remission at 1 Year Among a Multicenter Cohort of Patients with Inflammatory Bowel Disease Treated with Vedolizumab. [2023]

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

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

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

Review of vedolizumab for the treatment of ulcerative colitis. [2020]

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

Vedolizumab: an α4β7 integrin inhibitor for inflammatory bowel diseases. [2018]

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

Vedolizumab treatment persistence and safety in a 2-year data analysis of an extended access programme. [2022]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Vedolizumab as the first line of biologic therapy for ulcerative colitis and Crohn's disease - a systematic review with meta-analysis. [2023]

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

Real-World Effectiveness of Vedolizumab Dose Escalation in Patients With Inflammatory Bowel Disease: A Systematic Literature Review. [2023]

12. Spain pubmed.ncbi.nlm.nih.gov

Questions and answers about the management of Crohn's disease and ulcerative colitis with vedolizumab. [2020]

13. England pubmed.ncbi.nlm.nih.gov

Real-world outcomes of 54-week vedolizumab therapy and response durability after treatment discontinuation in ulcerative colitis: results from a multicenter prospective POLONEZ study. [2023]