Tildrakizumab for Pediatric Psoriasis

Recruiting at70 trial locations

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Recruiting

Sponsor: Sun Pharma Global FZE

Disqualifiers: Non-plaque psoriasis, Lab abnormalities, Infections, HIV, others

No Placebo Group

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial involves studying how a drug moves through and is processed by the bodies of children. It first examines older children and then younger children. The goal is to understand how the drug is absorbed, distributed, metabolized, and excreted in these age groups.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop your current medications. However, you cannot use topical therapy, phototherapy, or additional systemic therapy for psoriasis during the trial.

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 multiple clinical trials, including the phase III reSURFACE trials, which led to its approval by the US FDA. ^{1 2 3 4 5}

Is Tildrakizumab safe for use in humans?

Tildrakizumab has been shown to be generally safe in humans, with most adverse events being mild, such as upper respiratory tract infections and headaches. Nonclinical studies in monkeys also showed it was well tolerated at doses much higher than those used in humans, with no significant toxic effects. ^{1 2 6 7 8}

How does the drug Tildrakizumab differ from other treatments for pediatric psoriasis?

Tildrakizumab is unique because it specifically targets and blocks a protein called IL-23, which plays a key role in the inflammation process of psoriasis, offering a more targeted approach compared to broader immunosuppressive treatments. ^{9 10 11 12 13}

Research Team

Eligibility Criteria

This trial is for children and teens aged 6 to <18 with moderate to severe plaque psoriasis, who haven't responded well to topical treatments or phototherapy. They must weigh at least 15 kg and have a confirmed diagnosis of plaque psoriasis for over six months. Participants should not have recent serious infections, HIV, hepatitis B/C, significant lab abnormalities, or be pregnant.

Inclusion Criteria

A maximum of 2 QuantiFERON tests will be allowed. A re-test is only permitted if the first is indeterminate; the result of the second test will then be used.

My psoriasis is severe, affecting over 10% of my body.

My psoriasis is not well-controlled with creams, light therapy, or previous medications.

Exclusion Criteria

Your blood test results show high levels of certain substances, like ALT, AST, creatinine, or bilirubin, or low levels of white blood cells, which could affect your ability to take part in the study or affect the study results.

I am not pregnant, do not plan to become pregnant soon, and am not breastfeeding.

You have tested positive for HIV, hepatitis B, or hepatitis C.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part A: Open Label PK Study

Open label pharmacokinetics study conducted initially in adolescents (12 to <18 years) followed by younger cohort (6 to <12 years)

8 weeks

Part B: Randomized Trial Component

Randomized, placebo and active comparator-controlled study with withdrawal and retreatment after relapse

52 weeks

Part C: Open Label Long Term Extension (LTE)

Participants may opt into continuation of treatment long-term

Long-term (up to Week 108)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Etanercept (TNF-alpha Inhibitor)
• Placebo ()
• Tildrakizumab (Monoclonal Antibodies)

Trial Overview The study tests Tildrakizumab's effects on pediatric chronic plaque psoriasis. It starts with an open-label phase to understand how the body processes the drug (pharmacokinetics), followed by a randomized comparison with Etanercept and placebo, then a long-term extension phase for further evaluation.

Participant Groups

Group I: Part C: LTE Experimental Treatment 1 Intervention

Group II: Part B-1 and B-2: Randomized withdrawal and retreatment after relapse Experimental Treatment 2 Interventions

Group III: Part B Part 1: Placebo and active comparator controlled study Experimental Treatment 3 Interventions

Group IV: Part B 3: Efficacy and Safety Follow-up Active Control 1 Intervention

Group V: Part A Active Control 1 Intervention

Part A is a DOSE FINDING COMPONENT: OPEN LABEL PK lead-in and safety component

Who Is Running the Clinical Trial?

Sun Pharma Global FZE

Lead Sponsor

Trials

34

Recruited

10,200+

Sun Pharmaceutical Industries Limited

Lead 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]

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 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 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, a monoclonal antibody targeting interleukin-23, was found to be well tolerated in cynomolgus monkeys during a 9-month study with no significant toxicological findings, even at doses 90 times higher than the recommended human dose.

The nonclinical safety studies, including assessments of reproductive and developmental effects, support the safety of tildrakizumab for treating moderate to severe plaque psoriasis, with no adverse effects observed on fetal development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonclinical safety of tildrakizumab, a humanized anti-IL-23p19 monoclonal antibody, in nonhuman primates. Santostefano, M., Herzyk, D., Montgomery, D., et al.[2020]

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]

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]

A 3-year-old boy with recurrent viral infections exhibited an unusual CD16 phenotype on his natural killer (NK) cells, which may indicate a potential immunodeficiency related to his NK cell function.

Genetic analysis revealed a specific mutation in the Fc gamma RIIIA gene that alters the CD16 receptor, suggesting that this change could be linked to the boy's increased susceptibility to viral infections, warranting further investigation into the clinical implications of this genotype.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of an unusual Fc gamma receptor IIIa (CD16) on natural killer cells in a patient with recurrent infections. de Vries, E., Koene, HR., Vossen, JM., et al.[2021]

In a Phase I/II trial involving 7 patients with psoriatic arthritis (PsA), the humanized anti-CD3 monoclonal antibody huOKT3gamma1(ala-ala) showed promising efficacy, with 6 out of 7 patients experiencing over 75% improvement in inflamed joints and a 63% reduction in pain after 30 days.

The treatment was generally safe, with no significant side effects in patients receiving lower doses, although mild cytokine release symptoms were observed in one patient at a higher dose, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modified anti-CD3 therapy in psoriatic arthritis: a phase I/II clinical trial. Utset, TO., Auger, JA., Peace, D., et al.[2022]

In a study using wild-type and FcgammaR knock-out mice, the TA99 antibody significantly reduced lung metastases in metastatic melanoma, highlighting its efficacy in targeting the gp75 tumor antigen.

The study identified FcgammaRI (CD64) as the key receptor mediating the antitumor effects of TA99, and found that combining TA99 with the TLR-4 agonist MPL enhanced its protective effects, further emphasizing the importance of FcgammaRI in this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The high-affinity IgG receptor, FcgammaRI, plays a central role in antibody therapy of experimental melanoma. Bevaart, L., Jansen, MJ., van Vugt, MJ., et al.[2021]

Alefacept is an effective treatment for chronic plaque psoriasis, safely reducing disease symptoms by selectively inducing apoptosis in CD2(+) memory-effector T cells, as shown in phase II and III clinical trials.

The mechanism of action involves alefacept activating intracellular signals through interactions with CD2 and Fc gamma RIII (CD16), which leads to the activation of immune cells and the induction of apoptosis in target cells, highlighting its role as an immunomodulatory agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alefacept, an immunomodulatory recombinant LFA-3/IgG1 fusion protein, induces CD16 signaling and CD2/CD16-dependent apoptosis of CD2(+) cells. da Silva, AJ., Brickelmaier, M., Majeau, GR., et al.[2019]

A study of 87 donors revealed that the Fc gamma receptor IIIa (CD16) polymorphism at position 158 significantly affects IgG binding, with the 158V variant binding more IgG than the 158F variant.

The findings suggest that the differences in IgG binding among various Fc gammaRIIIa isoforms are linked to the 158V/F polymorphism, indicating its potential role in immune response variations among individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fc gammaRIIIa-158V/F polymorphism influences the binding of IgG by natural killer cell Fc gammaRIIIa, independently of the Fc gammaRIIIa-48L/R/H phenotype. Koene, HR., Kleijer, M., Algra, J., et al.[2022]

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

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

4. 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]

5. 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]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Nonclinical safety of tildrakizumab, a humanized anti-IL-23p19 monoclonal antibody, in nonhuman primates. [2020]

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

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

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

Identification of an unusual Fc gamma receptor IIIa (CD16) on natural killer cells in a patient with recurrent infections. [2021]

10. Canada pubmed.ncbi.nlm.nih.gov

Modified anti-CD3 therapy in psoriatic arthritis: a phase I/II clinical trial. [2022]

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

The high-affinity IgG receptor, FcgammaRI, plays a central role in antibody therapy of experimental melanoma. [2021]

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

Alefacept, an immunomodulatory recombinant LFA-3/IgG1 fusion protein, induces CD16 signaling and CD2/CD16-dependent apoptosis of CD2(+) cells. [2019]

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

Fc gammaRIIIa-158V/F polymorphism influences the binding of IgG by natural killer cell Fc gammaRIIIa, independently of the Fc gammaRIIIa-48L/R/H phenotype. [2022]