PsoriasisPhase 4NCT05110313

Effects of Tildrakizumab on Epigenetic Age

A Phase 4 study testing TILDRAKIZUMAB in people with Psoriasis and Aging, run by Carlos Wambier at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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. Read more about this study

Who is it for?: Ages 35 years and olderHealthy volunteers can take part
Conditions the study is for: Psoriasis, Aging, Epigenetic Disorder
What is being tested?: TILDRAKIZUMAB
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 30 participants
Where: 1 siteUnited States
Study dates: 8 Apr 2022to 27 May 2024
Phase: Phase 4
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 35 years and older
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.
Psoriasis patients who have chronic or recurring infections. Positive QuantiFERON upon screening will be exclusionary for this trial (latent tuberculosis).
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.

Trial locations and contacts

1 site in 1 country.

United States1 site

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

Other trials in United States

About this study

Official title: 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.

Read the detailed description

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
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.
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.

Conditions: Psoriasis, Aging, Epigenetic Disorder, Inflammation; Skin
Being tested: TILDRAKIZUMAB
Keywords: Epigenetic aging, DNA methylation, interleukin (IL)-23, Neutrophilic inflammation, Psoriasis, Aging, Transcriptome
Medical subject headings: Psoriasis, Dermatitis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TILDRAKIZUMABBiological
Also called ILUMYA™, tildrakizumab-asmn, ATC CODE: L04AC17 (WHO)
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.

Study groups in NCT05110313
Study group	Role	What they receive
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). Receives: Biological: TILDRAKIZUMAB
NON-PSORIASIS	No intervention	No intervention. Total of 10 subjects (5 male, 5 female).

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: Baseline and treatment weeks 28 and 52.

Secondary outcomes (2)

Evaluate the transcriptomic impact of tildrakizumab therapy in patients with psoriasis
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.
Measured: Baseline and treatment week 28.
Effects of individual characteristics on tildrakizumab response
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.
Measured: Baseline and treatment weeks 28 and 52.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

8 Apr 202227 May 2024

First posted5 Nov 2021
Study start8 Apr 2022
Primary completion24 May 2024
Study completion27 May 2024

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (20)Papers the sponsor has linked to this study.
Other trials for PsoriasisStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Basic science
Allocation: Non-randomised
Intervention model: Parallel groups
Model description: 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).
Masking: None (open label)
Enrolment: 30 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05110313
Sponsor's protocol ID: 420620
Other IDs: 20-056
Status last verified: Jul 2024
First submitted: 26 Oct 2021
Last updated: 18 Jul 2024
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Lowes MA, Bowcock AM, Krueger JG. Pathogenesis and therapy of psoriasis. Nature. 2007 Feb 22;445(7130):866-73. doi: 10.1038/nature05663.
PubMed 17314973
Kurd SK, Gelfand JM. The prevalence of previously diagnosed and undiagnosed psoriasis in US adults: results from NHANES 2003-2004. J Am Acad Dermatol. 2009 Feb;60(2):218-24. doi: 10.1016/j.jaad.2008.09.022. Epub 2008 Nov 20.
PubMed 19022533
Li WQ, Cho E, Weinstock MA, Mashfiq H, Qureshi AA. Epidemiological Assessments of Skin Outcomes in the Nurses' Health Studies. Am J Public Health. 2016 Sep;106(9):1677-83. doi: 10.2105/AJPH.2016.303315. Epub 2016 Jul 26.
PubMed 27459457
Li W, Han J, Hu FB, Curhan GC, Qureshi AA. Psoriasis and risk of type 2 diabetes among women and men in the United States: a population-based cohort study. J Invest Dermatol. 2012 Feb;132(2):291-8. doi: 10.1038/jid.2011.319. Epub 2011 Oct 13.
PubMed 21993559
Li WQ, Han JL, Manson JE, Rimm EB, Rexrode KM, Curhan GC, Qureshi AA. Psoriasis and risk of nonfatal cardiovascular disease in U.S. women: a cohort study. Br J Dermatol. 2012 Apr;166(4):811-8. doi: 10.1111/j.1365-2133.2011.10774.x.
PubMed 22175820
Li WQ, Han JL, Chan AT, Qureshi AA. Psoriasis, psoriatic arthritis and increased risk of incident Crohn's disease in US women. Ann Rheum Dis. 2013 Jul;72(7):1200-5. doi: 10.1136/annrheumdis-2012-202143. Epub 2012 Aug 31.
PubMed 22941766
Merola JF, Wu S, Han J, Choi HK, Qureshi AA. Psoriasis, psoriatic arthritis and risk of gout in US men and women. Ann Rheum Dis. 2015 Aug;74(8):1495-500. doi: 10.1136/annrheumdis-2014-205212. Epub 2014 Mar 20.
PubMed 24651620
Ryan C, Korman NJ, Gelfand JM, Lim HW, Elmets CA, Feldman SR, Gottlieb AB, Koo JY, Lebwohl M, Leonardi CL, Van Voorhees AS, Bhushan R, Menter A. Research gaps in psoriasis: opportunities for future studies. J Am Acad Dermatol. 2014 Jan;70(1):146-67. doi: 10.1016/j.jaad.2013.08.042. Epub 2013 Oct 11.
PubMed 24126079
Gudjonsson JE, Krueger G. A role for epigenetics in psoriasis: methylated Cytosine-Guanine sites differentiate lesional from nonlesional skin and from normal skin. J Invest Dermatol. 2012 Mar;132(3 Pt 1):506-8. doi: 10.1038/jid.2011.364.
PubMed 22327261
Nelson HH, Kelsey KT. Epigenetic epidemiology as a tool to understand the role of immunity in chronic disease. Epigenomics. 2016 Aug;8(8):1007-9. doi: 10.2217/epi-2016-0055. Epub 2016 Jul 13. No abstract available.
PubMed 27411030
Horvath S. DNA methylation age of human tissues and cell types. Genome Biol. 2013;14(10):R115. doi: 10.1186/gb-2013-14-10-r115.
PubMed 24138928
Bocklandt S, Lin W, Sehl ME, Sanchez FJ, Sinsheimer JS, Horvath S, Vilain E. Epigenetic predictor of age. PLoS One. 2011;6(6):e14821. doi: 10.1371/journal.pone.0014821. Epub 2011 Jun 22.
PubMed 21731603
Hannum G, Guinney J, Zhao L, Zhang L, Hughes G, Sadda S, Klotzle B, Bibikova M, Fan JB, Gao Y, Deconde R, Chen M, Rajapakse I, Friend S, Ideker T, Zhang K. Genome-wide methylation profiles reveal quantitative views of human aging rates. Mol Cell. 2013 Jan 24;49(2):359-367. doi: 10.1016/j.molcel.2012.10.016. Epub 2012 Nov 21.
PubMed 23177740
Marioni RE, Shah S, McRae AF, Chen BH, Colicino E, Harris SE, Gibson J, Henders AK, Redmond P, Cox SR, Pattie A, Corley J, Murphy L, Martin NG, Montgomery GW, Feinberg AP, Fallin MD, Multhaup ML, Jaffe AE, Joehanes R, Schwartz J, Just AC, Lunetta KL, Murabito JM, Starr JM, Horvath S, Baccarelli AA, Levy D, Visscher PM, Wray NR, Deary IJ. DNA methylation age of blood predicts all-cause mortality in later life. Genome Biol. 2015 Jan 30;16(1):25. doi: 10.1186/s13059-015-0584-6.
PubMed 25633388
Christiansen L, Lenart A, Tan Q, Vaupel JW, Aviv A, McGue M, Christensen K. DNA methylation age is associated with mortality in a longitudinal Danish twin study. Aging Cell. 2016 Feb;15(1):149-54. doi: 10.1111/acel.12421. Epub 2015 Nov 17.
PubMed 26594032

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruitingPhase 2
Extension Study of Safety and Tolerability of DDY391 in Participants With Moderate to Severe Psoriatic Arthritis (CDDY391A12201-extension)
Moderate to Severe Psoriatic Arthritis
Recruiting
Efficacy of a Self-Management Smartphone App to Improve Safety Skills in Patients With Inflammatory Arthritis
Rhumatoid Arthisis, Spondyloarthritis (SA)
Active, not recruitingPhase 2
Dose Ranging Study of ORKA-001 in Patients With Moderate-to-Severe Plaque Psoriasis
Plaque Psoriasis
RecruitingPhase 1
A Study of HB0017 Injection in Healthy Volunteers to Evaluate Safety and Tolerability of a Single Subcutaneous Injection in Low-Body-Weight Subjects; and Pharmacokinetics at Different Subcutaneous Injection Sites at the Same Dose
Psoriasis, Ankylosing Spondylitis
RecruitingPhase 1
A Study to Learn if Bimekizumab Given in Different Ways is Safe and Moves Similarly Throughout the Body Over Time in Adults
Psoriatic Arthritis, Axial Spondyloarthritis

All Psoriasis trials

Study at a glance

From the registry record, last updated by the sponsor on 18 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Effects of Tildrakizumab (ILUMYA) Use on Epigenetic Age Acceleration and Psoriasis
ClinicalTrials.gov ID: NCT05110313
Acronym / sponsor ID: 420620
Conditions: Psoriasis, Aging, Epigenetic Disorder, Inflammation; Skin
Keywords: Epigenetic aging, DNA methylation, interleukin (IL)-23, Neutrophilic inflammation, Psoriasis, Aging, Transcriptome
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 30 participants (actual)
Lead sponsor: Carlos WambierUniversity, hospital or other
Collaborators: Sun Pharmaceutical Industries Limited, Brown University, Lifespan, Ocean State Research Institute, Inc.
Study start: 8 Apr 2022 (actual)
Primary completion: 24 May 2024 (actual)
Study completion: 27 May 2024 (actual)
First posted: 5 Nov 2021 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

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

Trial Duration: One year.

Detailed description

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
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.
Objective

Study design

Primary purpose: Basic science
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2
Model description: 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).

Arm	Type	Receives
PSORIASIS TREATMENT	Experimental	Biological: TILDRAKIZUMAB1 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).
NON-PSORIASIS	No intervention	–No intervention. Total of 10 subjects (5 male, 5 female).

Who may qualify

Ages: 35 years and older
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

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.

Key exclusion criteria (7 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
TILDRAKIZUMABAlso: ILUMYA™, tildrakizumab-asmn, ATC CODE: L04AC17 (WHO)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.	Biological	PSORIASIS TREATMENT

Primary outcome

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.
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.

2 secondary outcomes

Evaluate the transcriptomic impact of tildrakizumab therapy in patients with psoriasis
Time frame: Baseline and treatment week 28.
Effects of individual characteristics on tildrakizumab response
Time frame: Baseline and treatment weeks 28 and 52.

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2024.
Background: PubMed 17314973Lowes MA, Bowcock AM, Krueger JG. Pathogenesis and therapy of psoriasis. Nature. 2007 Feb 22;445(7130):866-73. doi: 10.1038/nature05663.
Background: PubMed 19022533Kurd SK, Gelfand JM. The prevalence of previously diagnosed and undiagnosed psoriasis in US adults: results from NHANES 2003-2004. J Am Acad Dermatol. 2009 Feb;60(2):218-24. doi: 10.1016/j.jaad.2008.09.022. Epub 2008 Nov 20.
Background: PubMed 27459457Li WQ, Cho E, Weinstock MA, Mashfiq H, Qureshi AA. Epidemiological Assessments of Skin Outcomes in the Nurses' Health Studies. Am J Public Health. 2016 Sep;106(9):1677-83. doi: 10.2105/AJPH.2016.303315. Epub 2016 Jul 26.
Background: PubMed 21993559Li W, Han J, Hu FB, Curhan GC, Qureshi AA. Psoriasis and risk of type 2 diabetes among women and men in the United States: a population-based cohort study. J Invest Dermatol. 2012 Feb;132(2):291-8. doi: 10.1038/jid.2011.319. Epub 2011 Oct 13.
Background: PubMed 22175820Li WQ, Han JL, Manson JE, Rimm EB, Rexrode KM, Curhan GC, Qureshi AA. Psoriasis and risk of nonfatal cardiovascular disease in U.S. women: a cohort study. Br J Dermatol. 2012 Apr;166(4):811-8. doi: 10.1111/j.1365-2133.2011.10774.x.
Background: PubMed 22941766Li WQ, Han JL, Chan AT, Qureshi AA. Psoriasis, psoriatic arthritis and increased risk of incident Crohn's disease in US women. Ann Rheum Dis. 2013 Jul;72(7):1200-5. doi: 10.1136/annrheumdis-2012-202143. Epub 2012 Aug 31.
Background: PubMed 24651620Merola JF, Wu S, Han J, Choi HK, Qureshi AA. Psoriasis, psoriatic arthritis and risk of gout in US men and women. Ann Rheum Dis. 2015 Aug;74(8):1495-500. doi: 10.1136/annrheumdis-2014-205212. Epub 2014 Mar 20.
Background: PubMed 24126079Ryan C, Korman NJ, Gelfand JM, Lim HW, Elmets CA, Feldman SR, Gottlieb AB, Koo JY, Lebwohl M, Leonardi CL, Van Voorhees AS, Bhushan R, Menter A. Research gaps in psoriasis: opportunities for future studies. J Am Acad Dermatol. 2014 Jan;70(1):146-67. doi: 10.1016/j.jaad.2013.08.042. Epub 2013 Oct 11.
Background: PubMed 22327261Gudjonsson JE, Krueger G. A role for epigenetics in psoriasis: methylated Cytosine-Guanine sites differentiate lesional from nonlesional skin and from normal skin. J Invest Dermatol. 2012 Mar;132(3 Pt 1):506-8. doi: 10.1038/jid.2011.364.
Background: PubMed 27411030Nelson HH, Kelsey KT. Epigenetic epidemiology as a tool to understand the role of immunity in chronic disease. Epigenomics. 2016 Aug;8(8):1007-9. doi: 10.2217/epi-2016-0055. Epub 2016 Jul 13. No abstract available.
Background: PubMed 24138928Horvath S. DNA methylation age of human tissues and cell types. Genome Biol. 2013;14(10):R115. doi: 10.1186/gb-2013-14-10-r115.
Background: PubMed 21731603Bocklandt S, Lin W, Sehl ME, Sanchez FJ, Sinsheimer JS, Horvath S, Vilain E. Epigenetic predictor of age. PLoS One. 2011;6(6):e14821. doi: 10.1371/journal.pone.0014821. Epub 2011 Jun 22.
Individual participant dataSharing planned: No

Related trials for Psoriasis

Not yet recruitingPhase 2
Extension Study of Safety and Tolerability of DDY391 in Participants With Moderate to Severe Psoriatic Arthritis (CDDY391A12201-extension)
Moderate to Severe Psoriatic Arthritis
Recruiting
Efficacy of a Self-Management Smartphone App to Improve Safety Skills in Patients With Inflammatory Arthritis
Rhumatoid Arthisis, Spondyloarthritis (SA)
Active, not recruitingPhase 2
Dose Ranging Study of ORKA-001 in Patients With Moderate-to-Severe Plaque Psoriasis
Plaque Psoriasis
RecruitingPhase 1
A Study of HB0017 Injection in Healthy Volunteers to Evaluate Safety and Tolerability of a Single Subcutaneous Injection in Low-Body-Weight Subjects; and Pharmacokinetics at Different Subcutaneous Injection Sites at the Same Dose
Psoriasis, Ankylosing Spondylitis
RecruitingPhase 1
A Study to Learn if Bimekizumab Given in Different Ways is Safe and Moves Similarly Throughout the Body Over Time in Adults
Psoriatic Arthritis, Axial Spondyloarthritis

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Carlos G Wambier, MD, PhD principal investigator

Department of Dermatology, Warren Alpert Medical School of Brown University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing TILDRAKIZUMAB in people with Psoriasis and Aging, run by Carlos Wambier at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Epigenetic aging in psoriatic patients. (time frame: Baseline). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05110313, which also lists 20 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jul 2024.