Evaluation of Safety and Immunogenicity of Recombinant Varicella Zoster Virus Glycoprotein E Vaccine in Patients with Psoriasis or Psoriatic Arthritis

The primary objective of this study is to investigate the **safety** of the Shingrix vaccine in terms of underlying disease activity in patients with **psoriasis** or **psoriatic arthritis**. This is clinically relevant as it assesses the potential impact of vaccination on the progression or exacerbation of these chronic inflammatory conditions, ensuring that the vaccine does not adversely affect the patients' disease state.

Secondary objectives include:

• Identifying if Shingrix vaccination in patients with psoriasis or psoriatic arthritis results in a high and stable cellular and humoral immune response.
• Determining the frequency of **herpes zoster** and post-herpetic neuralgia.
• Assessing the frequency and severity of post-vaccination adverse events (AEs) and serious adverse events (SAEs).
• Evaluating the frequency of injection site reactions.

The clinical trial involves participants diagnosed with **psoriasis vulgaris** and/or **psoriatic arthritis**. The study population includes both male and female subjects, aged between 18 and 75 years. Participants are required to have a score threshold of PASI ≤ 9 and DAPSA ≤ 14, depending on their specific condition. The trial does not include a vulnerable population. Participants must provide written informed consent, and women of childbearing potential are required to use specific contraceptive measures during the study period. The sponsor has not provided information regarding the total number of participants. The selection criteria ensure that individuals with controlled disease activity are included, allowing for a focused investigation into the safety of the vaccine concerning underlying disease activity.

The clinical trial is designed to evaluate the **safety** and **immunogenicity** of the Shingrix vaccine in patients diagnosed with **psoriasis vulgaris** and/or **psoriatic arthritis**. This is a Phase IV, randomized, double-blind, controlled trial. The trial will commence on February 20, 2024, and is expected to conclude by July 31, 2026. Participants will be involved in the study for a maximum of 52 weeks, with the primary objective being to assess any increase in disease activity as measured by DAPSA and PASI scores within 12 weeks post-vaccination.

Study visits will follow a structured sequence, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (18-75 years), diagnosis, and disease activity scores. Participants will provide written informed consent and, if applicable, adhere to contraceptive measures. The trial includes follow-up visits at 8 and 52 weeks post-first vaccination to monitor the humoral and cell-mediated vaccine response. Additional visits will be scheduled for physical examinations, vital signs assessments, and laboratory tests to evaluate adverse events and injection site reactions.

The end-of-study visit will occur at the conclusion of the participant's involvement, approximately 60 days after the second vaccination. Conditions that may lead to early termination from the study include significant increases in disease activity or adverse events that compromise participant safety. The trial will ensure rigorous monitoring to maintain participant safety and data integrity throughout the study duration.

The clinical trial involves the administration of **Shingrix**, a **Herpes zoster vaccine** (recombinant, adjuvanted), developed by GlaxoSmithKline Biologicals S.A. The vaccine is presented as a **powder and suspension for suspension for injection**. The active substance in Shingrix is **recombinant varicella zoster virus glycoprotein E**, which is a structurally diverse substance classified as a vaccine. The pharmaceutical form of the product is a **suspension for injection**, and it is administered via the **intramuscular route**. The dosing regimen involves a maximum daily dose of 0.5 ml, with a total maximum dose of 1 ml over the course of the treatment. The maximum treatment period is set at 8 weeks.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on evaluating the safety and immunogenicity of the Shingrix vaccine in patients with psoriasis or psoriatic arthritis. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol. The trial aims to assess the safety of the vaccine in terms of its impact on the underlying disease activity in the target patient population.

Efficacy in this clinical trial will be assessed through both primary and secondary endpoints. The primary endpoint focuses on the increase in disease activity of **Psoriasis arthritis** and/or **Psoriasis vulgaris** following Shingrix vaccination. This is defined by an increase in DAPSA (by ≥ 15 points) or PASI (by ≥ 10 points) scores within 12 weeks after the first vaccination. If activity arises in patients who only had one condition at inclusion, the trial steering committee will adjudicate whether this should be considered an increase in activity.

Secondary endpoints include the number of patients with a humoral and cell-mediated vaccine response against the recombinant zoster vaccine (RZV), measured by an increase in titer (anti VZV-ELISA) and/or glycoprotein E positive CD4-T-Cells at 8 and 52 weeks post-first vaccination. Additionally, the rate of patients with herpes zoster (HZ) and post-herpetic neuralgia during the treatment phase and follow-up will be evaluated, with HZ confirmed via laboratory PCR. Ad-hoc visits will be conducted at the time of primarily suspected HZ. Other secondary endpoints include the assessment of adverse events (AEs/SAEs), physical examination, vital signs, and clinical chemistry during the treatment phase up to 60 days after the second vaccination or any doses, as well as the frequency of injection site reactions, assessed by physical examination 7 days post-vaccination and patient reporting.