Effects of Tildrakizumab on Epigenetic Age

July 16, 2024 updated by: Carlos Wambier

Effects of Tildrakizumab (ILUMYA) Use on Epigenetic Age Acceleration and Psoriasis

Design: Single-center open-label clinical trial.

Objective: Evaluate if tildrakizumab reverses peripheral blood leukocyte DNA methylation (epigenetic aging) observed in chronic psoriasis.

Number of subjects: 30. Intervention group: 20 (10 men, 10 women) with moderate-to-severe psoriasis. Control group: 10 (5 men, 5 women) with other skin diagnosis.

Population: >35-year-old subjects will be recruited from Brown Dermatology clinics.

Biological samples: Blood samples will be collected for all subjects at screening, and weeks 16, 28 and 52. Urine pregnancy tests will be performed for females of childbearing potential at weeks 4, 16, and 28. Serum pregnancy test and QuantiFERON test for tuberculosis will be performed at screening visit.

Safety parameters: Adverse events, and screening, week 16, week 28 blood samples laboratory results. Females of childbearing potential: serum pregnancy test at screening visit, urine pregnancy test at weeks 4, 16, and 28. Data Safety Monitoring Board will review data and laboratory flags quarterly.

Study center: Rhode Island Hospital, Providence, RI, USA.

Trial Duration: One year.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

  1. Introduction

    Psoriasis is a common, chronic, inflammatory disorder that affects millions of individuals worldwide.1,2 Although psoriasis etiology is still largely unknown and its precision management remains to be improved, advances in understanding the pathogenic cytokine network of psoriasis have led to the development of biologic therapy, such as FDA-approved on-label indication for moderate-to-severe psoriasis of tildrakizumab-asmn (ILUMYA, Sun Pharma Global, Princeton, NJ), an injectable monoclonal antibody that inhibit interleukin (IL)-23, a pro-inflammatory cytokine. Epidemiologic studies have promoted the recognition of psoriasis as a systemic disorder.3 Associations between psoriasis and incident risk of diabetes, cardiovascular disease, Crohn's disease, and gout have been reported in prospective studies.4-7 However, the mechanism underlying the systemic manifestations has been a knowledge gap for research on psoriasis.8

  2. Epigenetic aging (DNA methylation)

    The complex interplay of genetic and environmental factors in psoriasis may occur through the epigenetic mechanisms. DNA methylation of cytosine followed by guanine residues (CpG dinucleotides), the epigenetic process that participates in the transcriptional regulation and gene expression, has been linked to psoriasis.9 As the precise pathogenesis underlying the development of psoriasis remains largely undefined, further exploration of the role of epigenetics would offer a biologically plausible perspective to clarify psoriasis etiology. Epigenetic epidemiology would serve as a tool to elucidate the susceptibility and to identify novel biomarkers for psoriasis.10 The epigenetic clock is a novel biomarker of aging, developed based on DNA methylation.11-13 The epigenetic clock may capture aspects of "biological age" and older epigenetic age of blood has been associated with all-cause mortality,14,15 obesity,16 and many diseases.17-20 Although whether epigenetic age is associated with psoriasis is not yet known, previous research from our group recently found that average epigenetic age in psoriasis patients was 5 years higher than their corresponding chronological age (data not published), suggesting possible epigenetic age acceleration in psoriasis. Therefore, epigenetic age acceleration may serve as a novel biomarker for psoriasis and its systemic manifestations. It may also potentially be used as an intermediate biomarker assessing the systemic effects of tildrakizumab.

    Blood-based measures of epigenetics have the advantage of interrogating the systemic health status or treatment responses and assessing biomarkers across a large variety of disease domains.10,21

    Rationale for the study:

    Although epigenetic changes are tissue-specific, the connections between epigenetic epidemiology and psoriasis in blood-based epigenetic studies would decipher novel systemic inflammation and immune states of psoriasis and elucidate the effect of tildrakizumab use on the epigenetic age acceleration. Comprehensive assessment of epigenetic age acceleration in blood leukocytes between psoriasis and controls, and the change in epigenetic age acceleration after tildrakizumab initiation may lead to the identification of methylation markers for predicting the systemic risk of psoriasis and the effect of tildrakizumab on psoriasis. If confirmed to be an intermediate marker for the effect of psoriasis therapy with tildrakizumab, epigenetic age may be used to better profile the beneficial role of immunomodulation, promoting the management of psoriasis and its systemic comorbidities.

    Psoriasis is an inflammatory disease of the skin and joints and has been recognized as a systemic disorder. In this proposed study, the investigators hypothesize that epigenetic age acceleration may be associated with psoriasis, and tildrakizumab may be able to affect the epigenetic age acceleration associated with psoriasis.

  3. Objective

To determine the association between epigenetic age acceleration and risk of psoriasis, and also to evaluate if tildrakizumab can reverse peripheral blood leukocyte DNA methylation (epigenetic aging) associated with chronic psoriasis.

Specific Aim 1: To examine the association between epigenetic age acceleration and psoriasis: by comparing the baseline samples of peripheral blood leukocyte genome-wide DNA methylation assay collected at screening for psoriasis patients and controls.

Specific Aim 2: To evaluate dynamic changes in epigenetic age of the on-label use of tildrakizumab (week 28 vs screening visit). And upon discontinuation (week 28 vs week 52). Assess if epigenetic age could be a marker for the effect of tildrakizumab on psoriasis through psoriasis severity scores.

Specific Aim 3: We will evaluate the transcriptomic impact of ILUMYA therapy in patients with psoriasis and possible correlation/association with Epigenetic changes, psoriasis severity scores, the presence of systemic comorbidities.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Clinical Trials Center for Skin Diseases: Rhode Island Hospital, 593 Eddy Street, Dermatology Research, Jane Brown Building, 1st floor, Room 115

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

35 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Age: 35 years of age or older.
  • Psoriasis subjects: moderate-to-severe psoriasis: PASI (Psoriasis Area and Severity Index ≥12) and a minimum Body Surface Area (BSA) involvement of 10%.
  • Control Subjects: other skin diseases without psoriasis.

Exclusion Criteria:

  1. Patients aged less than 35 years.
  2. Patients with previous skin cancer or other cancers.
  3. Women of childbearing potential without effective contraceptive method, or lactating women.
  4. Prisoners.
  5. Psoriasis patients who have had a severe allergic reaction to ILUMYA or any of its ingredients.
  6. Psoriasis patients who have chronic or recurring infections. Positive QuantiFERON upon screening will be exclusionary for this trial (latent tuberculosis).
  7. Any condition that, in the opinion of the investigator, may interfere with patient's ability to participate in the study, such as severe cognitive impairment or other comorbidities that would, in the opinion of the investigator, predictably limit compliance with the study plan.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: PSORIASIS TREATMENT
1 syringe containing 1 mL of 100 mg/mL tildrakizumab-asmn. 100mg delivered by subcutaneous injection at weeks 0, 4, 16 and 28. Total of 20 subjects (10 male, 10 female).
Biological: TILDRAKIZUMAB

ILUMYA (tildrakizumab-asmn) is a humanized IgG1/k monoclonal antibody that selectively binds to the p19 subunit of IL-23 and inhibits its interaction with the IL-23 receptor. IL-23 is a naturally occurring cytokine that is involved in inflammatory and immune responses.

ILUMYA injection for subcutaneous use is a sterile, clear to slightly opalescent, colorless to slightly yellow solution supplied in 1mL single-dose prefilled syringe which contains 100 mg of tildrakizumab-asmn formulated in: L-histidine (0.495 mg), L-histidine hydrochloride monohydrate (1.42 mg), polysorbate 80 (0.5 mg), sucrose (70.0 mg), and Water for Injection, USP with a pH of 5.7-6.3. ILUMYA is supplied in a single-dose prefilled syringe with a glass barrel and 29-gauge fixed, 1/2-inch needle.

Other Names:
  • ILUMYA™
  • tildrakizumab-asmn
  • ATC CODE: L04AC17 (WHO)
No Intervention: NON-PSORIASIS
No intervention. Total of 10 subjects (5 male, 5 female).

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Epigenetic aging in psoriatic patients.
Time Frame: Baseline

To examine the association between epigenetic age acceleration and psoriasis: by comparing the baseline samples of peripheral blood leukocyte genome-wide DNA methylation assay sample collected at the screening visit for psoriasis vs non-psoriasis patients.

The epigenetic aging test is based on the Methylation EPIC BeadChip (Illumina), covering over 850,000 methylation sites. Specific patterns and quantifications will be compared between groups.
Baseline
Dynamics of tildrakizumab on epigenetic aging of psoriatic patients.
Time Frame: Baseline and treatment weeks 28 and 52.

To evaluate dynamic effects and changes in epigenetic age of the on-label use of ILUMYA (week 28 vs screening visit). And upon discontinuation (week 28 vs week 52). Assess if epigenetic age could be a marker for the effect of ILUMYA on psoriasis through psoriasis severity scores.

Specific patterns and quantifications will be compared between timeframes.
Baseline and treatment weeks 28 and 52.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Evaluate the transcriptomic impact of tildrakizumab therapy in patients with psoriasis
Time Frame: Baseline and treatment week 28.
To evaluate the blood transcriptome changes with anti-IL-23 therapy in patients with psoriasis, and possible correlation/association with psoriasis severity scores (BSA, PASI and CAPP), serum markers, and the presence of systemic co-morbidities on epigenetic aging.
Baseline and treatment week 28.
Effects of individual characteristics on tildrakizumab response
Time Frame: Baseline and treatment weeks 28 and 52.
To evaluate the possible correlation/association with changes in psoriasis severity scores (BSA, PASI and CAPP) and the presence of systemic co-morbidities on epigenetic aging. Multivariate analysis will be conducted with variables that include, but are not limited to baseline epigenetic aging assay results, age, body mass index, previous diagnoses, and medical interventions.
Baseline and treatment weeks 28 and 52.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Carlos Wambier

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Brown University
Sun Pharmaceutical Industries Limited
Lifespan
Ocean State Research Institute, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Carlos G Wambier, MD, PhD, Department of Dermatology, Warren Alpert Medical School of Brown University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 8, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 24, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 27, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 26, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 26, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 5, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 18, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 16, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 420620
  • 20-056 (Other Identifier: Study ID Rhode Island Hospital)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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