Development of Predictive Psoriasis Response Endotypes Using Single Cell Transcriptomics

Development of Predictive Psoriasis Response Endotypes Using Single Cell Transcriptomics in Ustekinumab Responders Versus Non-responders

The investigators propose to improve the possibility of reaching skin resolution by identifying certain markers or gene patterns that may predict patient response to certain psoriasis drugs ahead of time, thus eliminating or reducing the trial-and-error approach often employed. The ability to rule out (or in) specific therapeutics based on predictive efficacy would lead to a more personalized approach for psoriasis treatment.

To do this, the investigators will be asking participants to try two different already on the market FDA-approved psoriasis drugs for 8 weeks at a time. The investigators will be monitoring participants skin for improvements as well as taking blood and skin samples at least three times. Investigators may also ask to take stool samples and/or skin swabs.

Study Overview

• Status: Recruiting
• Conditions: Psoriasis
• Intervention / Treatment: Drug: Ustekinumab

Detailed Description

Psoriasis is a chronic systemic skin disease in which pro-inflammatory molecules contribute to the development of scaled inflamed skin and other disease-associated comorbidities such as increased risk of depression, heart attack, stroke, and metabolic syndrome. Some lesion-derived cytokines/chemokines are released into systemic circulation and increase lesional severity. Given their importance in the pathogenesis of psoriasis, the interleukins 12 (IL-12) and 23 (IL-23) are significant targets of biologic therapies.

Importantly, psoriasis patients exhibit variable responses to treatments targeting interleukins; one size does not fit all for these therapeutics. Our preliminary data demonstrates individual skin improvement (Responders) as well as lack of skin improvement (Non-Responders) in patients treated with monoclonal antibody therapy specifically targeting the shared (p40) subunit common to IL-12 and IL-23 (ustekinumab/Stelara). Interestingly, some Non-Responders to ustekinumab respond well to inhibition of the IL-23 pathway via the unique p19 subunit. We hypothesize that the pattern of differentially expressed genes (DEGs) among Responders and Non-Responders following anti-IL-12 and anti-IL-23 therapy may enable us to predict the likelihood of patient response to p40 antagonism as well as antagonism of the p19 subunit of IL-23. Single cell transcriptome analysis will be used to generate gene expression patterns that identify variable patient response patterns (endotypes).

• Study Type: Interventional
• Enrollment (Estimated): 56
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Amy Johnson, MD; Phone Number: 216-286-7369; Email: Amy.Johnson@UHhospitals.org
• Study Contact Backup: Name: Amanda Davies, MBA; Phone Number: 216-844-7834; Email: Amanda.Davies@UHhospitals.org

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Recruiting
      • University Hospitals Cleveland Medical Center
      • Contact: Amy Johnson, MD; Phone Number: 216-286-7369; Email: Amy.Johnson@UHhospitals.org
      • Contact: Kevin Cooper, MD; Phone Number: 216-844-7834
      • Sub-Investigator: Neil Korman, MD
      • Sub-Investigator: Amy Johnson, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 89 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosed with plaque-type psoriasis defined by either:

  • A board-certified dermatologist, OR
  • Dermatology Nurse Practitioner, OR
  • Skin punch biopsy
• Insurance that includes an anti-p40 biologic (ustekinumab/.Stelara) and at least one anti-p19 biologic (guselkumab/Tremfya or risankizumab/Skyrizi)
• Must be naive to ustekinumab, guselkumab, and risankizumab.
• Involvement of body surface area (BSA) of at least 10% at screening and baseline visit.
• Able to give informed consent under IRB approval procedures

Exclusion Criteria:

• Pregnant, breastfeeding, or planning to get pregnant 8 weeks before, during, and 8 weeks after the study.
• Inability to provide informed consent
• Inability to secure ustekinumab and either gusekumab or risankizumab for use while on trial
• Use of tanning booths for at least 4 weeks prior to baseline visit
• Current or recent use of topical steroid, tar, phototherapy, Vitamin D, or retinoid therapy to target lesions for at least 2 weeks prior to baseline visit and for duration of trial
• Current or recent use of systemic or biologic therapy for at least 8 weeks prior to baseline visit
• Patients with psoriatic arthritis or other rheumatologic diseases (e.g., Crohn's disease).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; Patients will be treated with ustekinumab (90mg at week 0 and week 4 by subcutaneous injection) for 8 weeks followed by treatment with guselkumab (100mg at week 0 and week 4 by subcutaneous injection) or risankizumab (150mg at week 0 and week 4 by subcutaneous injection)	Drug: Ustekinumab; Subjects will receive ustekinumab for 8 weeks followed by guselkumab or risankizumab for 8 weeks.; Other Names: Risankizumab; Guselkumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of a unique differentially expressed gene set in patients with psoriasis that may predict disease response following antagonism to IL-12 and/or IL-23.	Single-cell RNA transcriptomics from whole blood isolate from identify unique differentially expressed gene sets in patients following antagomism to IL-12 and/or IL-23.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of a cell subset that is a modified and predictive of disease response following antagonism to IL-12 and/or IL-23	Single-cell RNA sequencing or flow cytometry to identify a cell subset that is a modified and predictive of disease response following antagonism to IL-12 and/or IL-23.	24 weeks

Collaborators and Investigators

• Sponsor: University Hospitals Cleveland Medical Center
• Collaborators: Case Western Reserve University; LEO Foundation
• Investigators: Principal Investigator: Kevin Cooper, MD, University Hospitals Cleveland Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: February 25, 2022
• First Submitted That Met QC Criteria: February 25, 2022
• First Posted (Actual): March 8, 2022

Study Record Updates

• Last Update Posted (Actual): April 2, 2026
• Last Update Submitted That Met QC Criteria: March 28, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: psoriasis; ustekinumab; guselkumab; risankizumab
• Additional Relevant MeSH Terms: Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases; Psoriasis; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Ustekinumab; guselkumab; risankizumab
• Other Study ID Numbers: STUDY20220893

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