Tildrakizumab for Psoriasis

(MINIMA Trial)

Overseen By Leanne Barrett Goldstein

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Marcelo F. Di Carli, MD, FACC

Must not be taking: Oral prednisone, Methotrexate

Disqualifiers: SLE, RA, HIV, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 24 weeks

36 Participants Needed

Trial Summary

What is the purpose of this trial?

Psoriasis, a common chronic inflammatory skin disease affecting approximately 2% of the population, is associated with increased cardiovascular (CV) risk. Despite the implication of inflammation in this excess risk, it remains unclear whether reducing inflammation reduces the risk of cardiac events. This study proposes to test whether Tildrakizumab, an FDA approved therapy for psoriasis that blocks IL-23 and the Th17 pathway of inflammation, improves coronary vascular function and coronary flow reserve, as measured by noninvasive imaging with cardiac positron emission tomography. In so doing, improvement in coronary vasoreactivity, endothelial function, and tissue perfusion may have beneficial effects on myocardial mechanics, left ventricular deformation and function and, ultimately, symptoms and prognosis. This research may offer novel insights into the contributors of CV risk in psoriasis and provide data to support the development of strategies to prevent cardiovascular events in psoriatic disease.

Will I have to stop taking my current medications?

If you have previously used biologic therapy, topical steroids, phototherapy, or other systemic therapies for psoriasis, you will need to stop taking them for a certain period before joining the trial. If you are on statin therapy, you must have been on a stable dose for at least 6 months before enrolling.

What data supports the effectiveness of the drug Tildrakizumab for treating psoriasis?

Tildrakizumab has been shown to be effective in treating moderate-to-severe chronic plaque psoriasis, as demonstrated by positive results from phase III clinical trials (reSURFACE 1 and reSURFACE 2) where it was superior to placebo and etanercept. It targets a specific part of the immune system (interleukin-23 p19) to help reduce symptoms. ^{1 2 3 4 5}

Is Tildrakizumab safe for humans?

Tildrakizumab has been shown to be generally safe and well-tolerated in clinical trials for psoriasis, with most side effects being mild, such as upper respiratory infections and headaches. ^{1 2 5 6 7}

What makes the drug Tildrakizumab unique for treating psoriasis?

Tildrakizumab is unique because it specifically targets the p19 subunit of interleukin-23, a protein involved in inflammation, without affecting other related proteins like IL-12, making it a targeted treatment for moderate-to-severe chronic plaque psoriasis. ^{1 2 4 8 9}

Research Team

Marcelo F Di Carli, MD

Principal Investigator

Brigham and Women's Hospital

Eligibility Criteria

Adults aged 18-90 with moderate-to-severe psoriasis and at least one cardiovascular risk factor can join this trial. They must have a stable statin dose for 6 months if applicable, and meet specific criteria like certain blood test results or body measurements. Those who've tried other psoriasis treatments need a wash-out period before starting.

Inclusion Criteria

I have stopped my previous skin treatments as required.

I have a heart risk factor like high cholesterol, diabetes, or a family history of heart disease.

I have metabolic syndrome with at least three of the specified conditions.

Exclusion Criteria

I am not on chronic oral prednisone >10mg/day, methotrexate, or other immunosuppressants.

I have not had serious infections or other cancers besides non-melanoma skin cancer in the last 5 years.

I have severe heart failure.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (virtual or in-person)

Baseline

Baseline imaging tests conducted and study drug dispensed

1 day

1 visit (in-person)

Treatment

Participants receive Tildrakizumab and are monitored for adverse events and compliance

24 weeks

2 visits (in-person)

Final Assessment

Final imaging tests conducted to assess changes in coronary flow reserve and myocardial function

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Tildrakizumab

Trial Overview The study is testing Tildrakizumab, an FDA-approved psoriasis drug that targets inflammation pathways, to see if it improves heart vessel function in people with psoriasis using advanced imaging techniques. The goal is to understand how reducing skin inflammation might lower the risk of heart problems.

Participant Groups

Group I: Subjects treated with Tildrakizumab Experimental Treatment 1 Intervention

Informed consent will be obtained from study participants willing to participate in MiNIMA. Study participants will then undergo the baseline rest/stress cardiac PET scan. The final PET scan will occur at 6 months after the intervention.

Tildrakizumab is already approved in European Union, United States for the following indications:

Approved in European Union as Ilumya for:

• Moderate to severe plaque psoriasis

Approved in United States as Ilumya for:

• Moderate to severe plaque psoriasis

Who Is Running the Clinical Trial?

Marcelo F. Di Carli, MD, FACC

Lead Sponsor

Trials

4

Recruited

100+

Findings from Research

Tildrakizumab is a monoclonal antibody that specifically targets interleukin-23 p19, which plays a key role in the inflammatory process of chronic plaque psoriasis.

The drug received FDA approval based on positive outcomes from the phase III reSURFACE clinical trial program, demonstrating its efficacy for adults with moderate-to-severe chronic plaque psoriasis who require systemic therapy or phototherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tildrakizumab: First Global Approval. Markham, A.[2020]

In a study of 51 patients with moderate-to-severe plaque psoriasis who had previously failed biologic treatments, tildrakizumab showed significant effectiveness, with a marked reduction in the Psoriasis Area Severity Index (PASI) score from 19.2 at baseline to 0.6 at 48 weeks (P < 0.001).

The treatment also led to substantial improvements in Body Surface Area (BSA) and Dermatology Life Quality Index (DLQI) scores, indicating enhanced quality of life for patients, with significant results observed at both 12 and 48 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and Safety After a Switch to Tildrakizumab: A Real World Multicenter Italian Study in Psoriasis. Di Brizzi, EV., Buononato, D., Benvenuto, P., et al.[2023]

In two phase 3 trials involving 1862 patients, tildrakizumab (200 mg and 100 mg) demonstrated significant efficacy in treating moderate-to-severe chronic plaque psoriasis, achieving PASI 75 responses in 62-66% of patients compared to only 6% in the placebo group.

Tildrakizumab was well tolerated, with serious adverse events being low and similar across all treatment groups, indicating a favorable safety profile for this new treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tildrakizumab versus placebo or etanercept for chronic plaque psoriasis (reSURFACE 1 and reSURFACE 2): results from two randomised controlled, phase 3 trials. Reich, K., Papp, KA., Blauvelt, A., et al.[2019]

In a 52-week study involving 237 adults with moderate-to-severe plaque psoriasis, tildrakizumab demonstrated high efficacy, with 90.91% of patients achieving at least a 75% reduction in psoriasis severity (PASI 75) and 58.68% achieving complete skin clearance (PASI 100) by Week 52.

The safety profile of tildrakizumab was favorable, with no significant adverse events reported, and no patients had to discontinue treatment due to side effects, indicating it is a well-tolerated option for psoriasis management in real-life settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-life effectiveness of tildrakizumab in chronic plaque psoriasis: A 52-week multicentre retrospective study-IL PSO (Italian landscape psoriasis). Narcisi, A., Valenti, M., Gargiulo, L., et al.[2023]

Tildrakizumab, an antibody for treating moderate-to-severe chronic plaque psoriasis, shows a favorable efficacy profile, with 62.2% of patients achieving a 75% improvement in psoriasis severity (PASI75) at week 12, based on data from three clinical trials involving 2,717 participants.

The recommended dosing regimen is 100 mg every 12 weeks for most patients, but those weighing over 90 kg may benefit from a higher dose of 200 mg every 12 weeks, ensuring optimized treatment based on body weight.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exposure-response characterisation of tildrakizumab in chronic plaque psoriasis: Pooled analysis of 3 randomised controlled trials. Kerbusch, T., Li, H., Wada, R., et al.[2021]

Tildrakizumab, an antibody targeting IL-23, was found to be safe and well tolerated in healthy adults, with mild adverse events like upper respiratory infections and headaches reported.

The pharmacokinetics showed that both intravenous and subcutaneous doses resulted in slow clearance and a long half-life, with subcutaneous bioavailability around 80%, indicating effective delivery of the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of Tildrakizumab (MK-3222), an Anti-IL-23 Monoclonal Antibody, After Intravenous or Subcutaneous Administration in Healthy Subjects. Khalilieh, S., Hodsman, P., Xu, C., et al.[2019]

In the TRIBUTE study involving 177 adult patients with moderate-to-severe plaque psoriasis, treatment with Tildrakizumab (TIL) 100 mg for 24 weeks resulted in significant improvements in psoriasis severity, with 88.4% of patients achieving a PASI score of ≤3 and 92.5% achieving PASI 75.

The treatment also led to notable enhancements in health-related quality of life, including reduced pruritus, pain, and improved sleep, with a high patient satisfaction score (mean TSQM score of 80.5), and a favorable safety profile with only one serious adverse event reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tildrakizumab improves high burden skin symptoms, impaired sleep and quality of life of moderate-to-severe plaque psoriasis patients in conditions close to clinical practice. Costanzo, A., Llamas-Velasco, M., Fabbrocini, G., et al.[2023]

In a phase IIb trial involving 355 adults with moderate-to-severe chronic plaque psoriasis, tildrakizumab demonstrated significant efficacy, with PASI 75 responses of up to 74.4% at week 16 compared to only 4.4% in the placebo group, indicating its effectiveness in reducing psoriasis severity.

Tildrakizumab was generally safe and well tolerated, with serious adverse events reported but not common, suggesting that targeting IL-23p19 could be a promising approach for psoriasis treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tildrakizumab (MK-3222), an anti-interleukin-23p19 monoclonal antibody, improves psoriasis in a phase IIb randomized placebo-controlled trial. Papp, K., Thaçi, D., Reich, K., et al.[2018]

In a study of 190 patients with moderate-to-severe plaque psoriasis treated with tildrakizumab for 24 weeks, there was an impressive 88.79% reduction in the Psoriasis Area and Severity Index (PASI), indicating significant effectiveness in managing the condition.

The treatment was found to be safe, with only a 5.9% rate of adverse events, primarily infections, and no significant differences in effectiveness based on factors like gender or prior biological therapy exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of tildrakizumab for the treatment of psoriasis in real-world settings at 24 weeks: A retrospective, observational, multicentre study by the Spanish Psoriasis Group. Berenguer-Ruiz, S., Aparicio-Domínguez, M., Herranz-Pinto, P., et al.[2023]

References

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

Tildrakizumab: First Global Approval. [2020]

2. Austria pubmed.ncbi.nlm.nih.gov

Effectiveness and Safety After a Switch to Tildrakizumab: A Real World Multicenter Italian Study in Psoriasis. [2023]

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

Tildrakizumab versus placebo or etanercept for chronic plaque psoriasis (reSURFACE 1 and reSURFACE 2): results from two randomised controlled, phase 3 trials. [2019]

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

Real-life effectiveness of tildrakizumab in chronic plaque psoriasis: A 52-week multicentre retrospective study-IL PSO (Italian landscape psoriasis). [2023]

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

Exposure-response characterisation of tildrakizumab in chronic plaque psoriasis: Pooled analysis of 3 randomised controlled trials. [2021]

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

Pharmacokinetics of Tildrakizumab (MK-3222), an Anti-IL-23 Monoclonal Antibody, After Intravenous or Subcutaneous Administration in Healthy Subjects. [2019]

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

Tildrakizumab improves high burden skin symptoms, impaired sleep and quality of life of moderate-to-severe plaque psoriasis patients in conditions close to clinical practice. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Tildrakizumab (MK-3222), an anti-interleukin-23p19 monoclonal antibody, improves psoriasis in a phase IIb randomized placebo-controlled trial. [2018]

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

Effectiveness and safety of tildrakizumab for the treatment of psoriasis in real-world settings at 24 weeks: A retrospective, observational, multicentre study by the Spanish Psoriasis Group. [2023]