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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether Tildrakizumab, a drug approved for treating psoriasis, can also improve heart health in people with psoriasis. The researchers aim to determine if reducing inflammation with this treatment can lower the risk of heart problems associated with psoriasis. Suitable participants have moderate-to-severe psoriasis and at least one heart disease risk factor, such as high blood pressure or a family history of heart issues. This study could uncover new ways to protect the heart in people living with psoriasis. As a Phase 4 trial, this research seeks to understand how the FDA-approved treatment benefits more patients, offering a chance to contribute to broader heart health insights.

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 is the safety track record for Tildrakizumab?

Research has shown that Tildrakizumab is generally safe for treating psoriasis. In earlier studies, people with moderate-to-severe plaque psoriasis used Tildrakizumab and tolerated it well, meaning it didn't cause unexpected problems. These trials revealed no new safety concerns. Another study found that Tildrakizumab remained safe for up to 72 weeks, which is more than a year. The FDA has approved this treatment for psoriasis, indicating it has been checked for safety. Overall, evidence supports Tildrakizumab as a safe option for people with psoriasis. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Tildrakizumab is unique because it targets a specific protein called IL-23, which plays a key role in the inflammatory process of psoriasis. Unlike many standard treatments that might target broader immune responses, Tildrakizumab's precise action on IL-23 can lead to fewer side effects and improved efficacy. Researchers are excited about this targeted approach because it offers the potential for better skin clearance and a more personalized treatment option for people with psoriasis.

What is the effectiveness track record for Tildrakizumab in treating psoriasis?

Research has shown that Tildrakizumab, the treatment under study in this trial, effectively treats moderate-to-severe plaque psoriasis. Studies have found that it consistently reduces psoriasis symptoms over several years. In everyday use, it effectively manages symptoms without introducing new safety issues. The treatment also quickly enhances patients' mental well-being. Additionally, it proved safe and effective for treating scalp psoriasis over a year. Since the FDA has already approved Tildrakizumab for psoriasis, it is considered a reliable treatment for this skin condition. ^{1 6 7 8 9}

Who Is on the Research Team?

Marcelo F Di Carli, MD

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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 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 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 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]

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]

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]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39093661/

Tildrakizumab Real-World Effectiveness and Safety Over ...

Tildrakizumab treatment was effective in adult patients with moderate-to-severe plaque psoriasis in real-world settings, with no new safety signals.

2.

ilumyapro.com

ilumyapro.com/ilumya-results

Pivotal Trial Data | ILUMYA® (tildrakizumab-asmn)

ILUMYA® PIVOTAL TRIAL RESULTS THROUGH 5 YEARS. ILUMYA® (tildrakizumab-asmn) provided consistent reduction of detectable psoriasis activity throughout the 5-year

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12219165/

52-week Interim Data of the Phase IV Positive Study

The results of the study showed that within 16 weeks of treatment, tildrakizumab quickly improved the psychological well-being of the people ...

4.

jaad.org

jaad.org/article/S0190-9622(24)03393-0/fulltext

Week 52 results from a phase 3b, randomized, double- ...

These results demonstrate that the efficacy and safety of tildrakizumab for the treatment of scalp psoriasis are maintained through 52 weeks. In ...

5.

academic.oup.com

academic.oup.com/bjd/article/193/3/442/8130694

Efficacy and safety of tildrakizumab in patients with early

Efficacy findings were supported in a subset of patients matched by disease duration. TEAEs and serious TEAEs occurred in 65.8% vs. 66.2% and ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01722331

NCT01722331 | A Study to Evaluate the Efficacy and ...

This study is being conducted to evaluate the efficacy and safety/tolerability of subcutaneous tildrakizumab (MK-3222), followed by an optional long-term safety ...

7.

ilumyapro.com

ilumyapro.com/scalp-psoriasis

Scalp Psoriasis Reduction - ILUMYA® (tildrakizumab-asmn)

SAFETY OUTCOMES IN SCALP PSORIASIS. No new safety signals detected through. Week 72 in Trial 42. SEE SUBGROUP SAFETY yellow-arrow. hello. INDICATION AND ...

8.

sciencedirect.com

sciencedirect.com/science/article/pii/S0003496724204799

Efficacy and safety of tildrakizumab in patients with active ...

Tildrakizumab was well tolerated through 52 weeks of treatment. These results support tildrakizumab phase III clinical development in PsA. Data availability ...

9.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7064936/

Long‐term efficacy and safety of tildrakizumab ...

Tildrakizumab 100 mg and 200 mg are efficacious and well tolerated with short‐term use in the treatment of patients with moderate‐to‐severe plaque psoriasis.