Tildrakizumab for Psoriasis

Overseen By Raymond Cho, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of California, San Francisco

Must not be taking: Systemic immunosuppressives

Disqualifiers: Pregnancy, Severe immunodeficiency, Tuberculosis, 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: Unknown

Duration: 3 months

10 Participants Needed

Trial Summary

What is the purpose of this trial?

This study aims to assess cutaneous and blood immune cell function of patients with psoriasis before and after initiation of treatment with the IL23 blocker, tildrakizumab.

Will I have to stop taking my current medications?

The trial requires that you have not taken systemic immunosuppressives (medications that suppress the immune system) in the last 4 weeks. If you are on such medications, you may need to stop them before participating.

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 found to be superior to placebo and etanercept. It works by targeting a specific part of the immune system (interleukin-23 p19) that is involved in the development of psoriasis. ^{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 tract infections and headaches. ^{1 2 5 6 7}

How is the drug Tildrakizumab different from other psoriasis treatments?

Tildrakizumab is unique because it specifically targets the p19 subunit of interleukin-23, a protein involved in inflammation, without affecting interleukin-12, which is different from some other treatments that target both. This specificity may lead to fewer side effects and improved effectiveness for moderate-to-severe chronic plaque psoriasis. ^{1 2 4 8 9}

Research Team

Raymond Cho, MD, PhD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

This trial is for adults over 18 with moderate to severe psoriasis, affecting more than 5% of their body. It's not suitable for those on systemic immunosuppressives in the last month, pregnant or breastfeeding individuals, people with severe immune deficiencies, active tuberculosis or other serious infections, and anyone with an active systemic cancer.

Inclusion Criteria

I am 18 years old or older.

My psoriasis is severe or covers more than 5% of my body.

My psoriasis covers more than 5% of my body.

Exclusion Criteria

I have not taken any immunosuppressive drugs in the last 4 weeks.

I have an active cancer that is affecting my whole body.

Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tildrakizumab and undergo biopsy and blood sample collection for molecular profiling

3 months

Multiple visits for sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Tildrakizumab

Trial Overview The study is testing Tildrakizumab injections to see how they affect skin and blood immune cells in psoriasis patients. The goal is to understand the changes in immune function after starting treatment with this IL23 blocker.

Participant Groups

Group I: Tildrakizumab treatment Experimental Treatment 1 Intervention

Biological/vaccine: tildrakizumab

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?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Sun Pharmaceutical Industries Limited

Industry Sponsor

Trials

71

Recruited

14,000+

Dilip Shanghvi

Sun Pharmaceutical Industries Limited

Chief Executive Officer since 1993

Majored in Cellular and Molecular Biology at the University of Michigan – Ann Arbor

Dr. Azadar H. Khan

Sun Pharmaceutical Industries Limited

Chief Medical Officer since 2023

MD from a recognized institution

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]