Psoriasis Clinical Trial: Current Research and Active Studies in Skin Treatment

Psoriasis clinical trials have become increasingly sophisticated in recent years, with regulatory agencies and pharmaceutical companies conducting extensive research into next-generation treatments. Current investigations span multiple therapeutic approaches, from interleukin-23 inhibitors to topical botanical compounds, all designed to improve upon existing standard-of-care options. Understanding the current trial landscape, the medications being tested, and the expected outcomes can help patients and healthcare providers make informed decisions about participation and treatment strategies.

Biologic Therapies and Interleukin Pathway Inhibition

A substantial portion of active psoriasis clinical trials focuses on biologic agents that target specific immune pathways. Risankizumab, an interleukin-23 inhibitor, continues to be evaluated in multiple trial settings. The KNOCKOUT study, a phase 2 investigation, examined higher-than-approved doses of risankizumab at 300 or 600 mg administered at weeks 0, 4, and 16, with participants monitored for 100 weeks without further dosing 11. Results from this trial demonstrated that at weeks 28 and 52, PASI 75/90/100 responses were 94.4% and 83.3% respectively in treatment groups, with no new safety signals identified 11.

Icotrokinra represents a first-in-class oral interleukin-23 receptor antagonist peptide now being evaluated across five phase 3 clinical trials 17. In the ICONIC-LEAD trial, icotrokinra achieved PASI 90 in 50% of treated patients compared to 4% receiving placebo at week 16, while Investigator's Global Assessment scores of 0 or 1 with at least 2-grade improvement were achieved by 65% versus 8% respectively 17. Clear skin outcomes occurred at higher rates in the icotrokinra group, with IGA 0 scores of 33% versus 1% in the placebo arm 17.

Comparative Efficacy Trials and Head-to-Head Studies

Researchers increasingly conduct head-to-head comparisons between approved and investigational agents to provide clinicians with evidence-based treatment guidance. The Zasocitinib Phase 3 trial, sponsored by Takeda, is comparing this novel agent against deucravacitinib in 606 participants across 113 locations in France, Japan, Poland, Canada, Bulgaria, Latvia, the United States, and Czechia 2. This randomized, double-blind study began enrollment on July 9, 2025, with a primary completion date of June 5, 2026 2. Participants take daily tablets of either zasocitinib or matching placebo alongside daily capsules of either over-encapsulated deucravacitinib or matching placebo for 16 weeks 2.

The IMMpactful trial published in Dermatology and Therapy compared risankizumab directly against deucravacitinib in adults with moderate plaque psoriasis who had not previously received biologic treatment. Over a 16-week period, a significantly higher proportion of risankizumab-treated patients achieved PASI 90 than those receiving deucravacitinib, with 57.3% versus 22.9% respectively 3. Similarly, sPGA 0/1 with at least a two-grade improvement from baseline was achieved by 80.2% of risankizumab patients compared to 39.7% of deucravacitinib patients 3.

Novel Oral Medications and Emerging Therapeutic Approaches

Oral medications continue to gain prominence in the psoriasis trial landscape. HS-20137, a novel interleukin-23 inhibitor, was evaluated in a randomized, double-blind, placebo-controlled phase 2 study conducted across 22 sites in mainland China from September 2023 to February 2025. The study enrolled 159 participants with moderate-to-severe psoriasis, with a mean baseline PASI score of 25.8 9. At week 16, significantly more patients treated with HS-20137 achieved PASI 90 compared to placebo, with responses ranging from 65.0% to 76.9% in HS-20137 groups versus only 7.5% in the placebo group 9. The PASI score significantly decreased in all treatment groups by 41.4% to 46.2% after the first injection at week 4 and was maintained through week 52 9.

The RAP-103 study, sponsored by Clarent Biopharma, is investigating an oral medication for adults aged 18 to 70 years with moderate to severe plaque psoriasis. Approximately 90 participants are being randomly assigned to receive either 400 mg of RAP-103 once daily, 200 mg twice daily, or matching placebo medications over an 8-week treatment period 10. Primary goals measure improvement using the Psoriasis Area and Severity Index (PASI75) and static Physician's Global Assessment (sPGA), with measurements occurring at baseline, 30 days, and 60 days 10.

Early-Phase Investigations and Novel Drug Classes

Early-stage clinical trials continue to explore innovative mechanisms of action. ZP9830, being investigated by Zealand Pharma, is undergoing evaluation in a phase 1 interventional trial assessing safety, tolerability, pharmacokinetics, and clinical efficacy over an 8-week treatment period in participants with plaque psoriasis 1. This randomized, double-blind, placebo-controlled study has an estimated enrollment of 32 participants and is recruiting at the Centre for Human Drug Research in Leiden, Netherlands 1. The trial contact information is available through Zealand Pharma's clinical operations department at +45 88 77 36 00 1.

ME3183, a novel phosphodiesterase 4 inhibitor, has demonstrated efficacy in a phase 2 trial involving 132 patients with moderate to severe plaque psoriasis. The randomized, double-blind, placebo-controlled study ran from March 28, 2022 to May 31, 2022 at 27 study sites in the United States and Canada 22. Participants were randomly assigned to receive ME3183 at dosages of 5 mg twice daily, 10 mg once daily, 7.5 mg twice daily, 15 mg once daily, or placebo 22. The trial demonstrated a favorable safety profile, with common adverse effects being mild to moderate, including diarrhea, nausea, and headache 22. ME3183 showed significant efficacy in reducing PASI scores, especially at 7.5 mg twice daily and 15 mg once daily, compared to placebo 22.

Topical Treatments and Botanical Compound Investigations

Topical formulations remain an important therapeutic avenue for mild-to-moderate psoriasis. The PLANTCOAT-III trial is a phase 3, randomized, quadruple-blinded, parallel-group study testing Total coumarin (TC) cream in 300 participants with psoriasis vulgaris 7. This botanical-derived treatment is being evaluated for both efficacy in improving disease symptoms and safety profile, with the trial currently recruiting participants 7. The study began on February 1, 2026, with a primary completion date of December 31, 2027 and estimated final completion on June 30, 2028 7. Eligibility criteria include adults aged 18 to 70 years with confirmed psoriasis vulgaris diagnosis.

Topical diacerein is being evaluated in a phase IV, randomized, placebo-controlled, double-blind clinical study conducted by Cairo University to evaluate safety and effectiveness in adults with psoriasis vulgaris. The primary objective compares the proportion of participants achieving clinically meaningful improvement in disease severity between topical diacerein 1% and placebo groups, applied twice daily for two months 5. Participants attend follow-up visits at weeks 2, 4, 6, and 8, with an additional evaluation one month after treatment cessation 5. The primary efficacy endpoint measures the proportion achieving at least 75% improvement from baseline in the Psoriasis Area and Severity Index (PASI 75) at week 8 5.

Population-Specific and Long-Term Safety Trials

Clinical trials increasingly address specific patient populations and long-term outcomes. The PRAGMATYK trial is a phase 3b/4 multi-center, randomized, open-label, long-term safety study comparing deucravacitinib to ustekinumab in participants with moderate-to-severe plaque psoriasis aged 40 years and older 4. Study recruitment began in September 2025 with an expected completion around January 2031, examining cardiovascular safety in a population with specific cardiovascular risk factors 4. Eligible participants must have at least 10% body surface area involvement and documented cardiovascular risk factors such as smoking, hypertension, dyslipidemia, diabetes, or family history of premature heart disease 4.

The VISIBLE trial is an ongoing, multicenter, double-blind, randomized phase 3b clinical trial evaluating guselkumab safety and efficacy in patients with skin of color across predominantly moderate to severe body plaque psoriasis and scalp psoriasis 14. Cohort A demonstrated that at week 16, significantly more patients receiving TREMFYA achieved Investigator's Global Assessment scores of 0 or 1 and PASI 90 compared to placebo recipients, with 74% and 57.1% respectively versus 0% and 3.8% 14. Cohort B examined moderate to severe scalp psoriasis specifically in participants across the skin-tone spectrum, enrolling 108 participants at 45 sites in the United States and Canada from September 2022 to June 2024 12.

Regulatory Pathways, Enrollment Requirements, and Participation Considerations

Prospective trial participants must understand the enrollment landscape, eligibility criteria variations, and what ongoing participation entails. Most moderate-to-severe plaque psoriasis trials require participants to be at least 18 years of age with documented diagnosis and baseline body surface area involvement typically ranging from 10% or greater. The TYK2 inhibitor trial being conducted in Shanghai, China, enrolls 140 estimated participants aged 18 to 70 years with body mass index between 18 and 40 kg/m2 and clinical diagnosis of plaque psoriasis for 6 months or longer 6. Women of childbearing potential and sexually active males must agree to follow contraception protocols throughout the study 6. Important exclusion criteria include active infections, malignancies, and certain cardiovascular conditions depending on trial-specific safety requirements.

Many trials involve decentralized or hybrid designs that reduce participant burden. The Magnolia officinalis dietary supplement study recruits 100 estimated participants to evaluate whether a consumer-grade supplement affects immune biomarkers in psoriasis 8. Participants take the supplement or placebo daily for 3 months, complete electronic questionnaires about quality of life and symptoms at baseline, 1 month, and 3 months, and use at-home blood collection kits to provide samples at the same intervals for analysis of inflammatory proteins 8. Reasonable study-related expenses are typically reimbursed, and there is no cost to participate. Trial durations vary substantially, from 8 weeks for some proof-of-concept studies to 5 years for long-term cardiovascular safety investigations, requiring participants to commit to regular study center visits ranging from 4 to 14 visits depending on the protocol.

Sources

1. ICH GCP Clinical Trials Registry (ZP9830 in Plaque Psoriasis)
2. Drug Landscape (NCT06973291 - Zasocitinib Phase 3 Trial)
3. Springer Nature Link (Risankizumab versus Deucravacitinib - IMMpactful Trial)
4. UC Davis Clinical Trials (PRAGMATYK - Deucravacitinib Versus Ustekinumab)
5. ICH GCP Clinical Trials Registry (Topical Diacerein in Psoriasis Vulgaris)
6. ICH GCP Clinical Trials Registry (TYK2 Inhibitor in Plaque Psoriasis)
7. Drug Landscape (NCT07426120 - PLANTCOAT-III Total Coumarin Cream)
8. ICH GCP Clinical Trials Registry (Magnolia Officinalis Dietary Supplement Study)
9. Springer Nature Link (HS-20137 for Moderate-to-Severe Psoriasis Phase 2 Study)
10. ICH GCP Clinical Trials Registry (RAP-103 Psoriasis Treatment Study)
11. Nature Communications (KNOCKOUT Study - Risankizumab High-Induction Dosing)
12. PubMed (Guselkumab for Moderate to Severe Scalp Psoriasis - VISIBLE Trial)
13. J&J Medical Connect (Icotrokinra - ICONIC-ASCEND Clinical Trial)
14. J&J Medical Connect (TREMFYA - VISIBLE Clinical Trial Overview)
15. TrialFinderData (NCT06979453 - Deucravacitinib in Adolescent Participants)
16. ICH GCP Clinical Trials Registry (HSK44459 in Moderate to Severe Plaque Psoriasis)
17. Springer Nature Link (Icotrokinra - Oral IL-23 Receptor Antagonist Review)
18. Dermatology Times (Novel PDE4 Inhibitor ME3183 Phase 2 Trial)
19. Springer Nature Link (Effectiveness and Durability of Risankizumab - PRIMMA Study)
20. ICH GCP Clinical Trials Registry (ORKA-001 in Plaque Psoriasis - EVERLAST-B)
21. Drug Landscape (NCT06073119 - SPECIFI-PSO SAR441566 Phase 2 Trial)
22. Dermatology Times (ME3183 PDE4 Inhibitor Phase 2 Results)