Effects of Tildrakizumab on Epigenetic Age

NCT05110313 | Completed Phase 4 DMC FDA Drug

• 2 other identifiers: 42062020-056
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Psoriasis; Aging; Epigenetic Disorder; Inflammation; Skin

Keywords

Epigenetic aging; DNA methylation; interleukin (IL)-23; Neutrophilic inflammation; Psoriasis; Aging; Transcriptome

Outcome Measures

Primary Outcomes (2)

• Epigenetic aging in psoriatic patients.

  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.

  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 Outcomes (2)

• Evaluate the transcriptomic impact of tildrakizumab therapy in patients with psoriasis

  Baseline and treatment week 28.

• Effects of individual characteristics on tildrakizumab response

  Baseline and treatment weeks 28 and 52.

Study Arms (2)

PSORIASIS TREATMENT

EXPERIMENTAL

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

NON-PSORIASIS

NO INTERVENTION

No intervention. Total of 10 subjects (5 male, 5 female).

Interventions

TILDRAKIZUMAB BIOLOGICAL

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.

Also known as: ILUMYA™, tildrakizumab-asmn, ATC CODE: L04AC17 (WHO)

PSORIASIS TREATMENT

Eligibility Criteria

• Age: 35 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Patients aged less than 35 years.
• Patients with previous skin cancer or other cancers.
• Women of childbearing potential without effective contraceptive method, or lactating women.
• Prisoners.
• Psoriasis patients who have had a severe allergic reaction to ILUMYA or any of its ingredients.
• 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.

Sponsors & Collaborators

• Carlos Wambier: lead
• Sun Pharmaceutical Industries Limited: collaborator
• Brown University: collaborator
• Lifespan: collaborator
• Ocean State Research Institute, Inc.: collaborator

Study Sites (1)

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

Providence, Rhode Island, 02903, United States

Location

Related Publications (19)

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Related Links

• Brown Dermatology Clinical Trials Website

MeSH Terms

Conditions

Psoriasis; Dermatitis

Interventions

tildrakizumab; World Health Organization

Condition Hierarchy (Ancestors)

Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

United Nations; International Agencies; Organizations; Health Care Economics and Organizations

Study Officials

• Carlos G Wambier, MD, PhD

  Department of Dermatology, Warren Alpert Medical School of Brown University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Dermatology, Clinician Educator

Model Details: We will enroll 30 subjects aged 35 years or older. Arm 1 (psoriasis treatment): 20 subjects with moderate-to-severe psoriasis (including 10 men and 10 women). Arm 2 (non-psoriasis, non-treatment): 10 age and sex matched controls without psoriasis (including 5 men and 5 women). The blood leukocytes will be collected to evaluate DNA methylation at baseline (week 0) for both arms. The psoriasis treatment arm will undergo blood leukocytes collection during treatment (at week 28) and post-treatment (week 52).

Study Record Dates

• First Submitted: October 26, 2021
• First Posted: November 5, 2021
• Study Start: April 8, 2022
• Primary Completion: May 24, 2024
• Study Completion: May 27, 2024
• Last Updated: July 18, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)