Effect of Secukinumab in the Treatment of Psoriatic Arthritis — SATURN  

Psoriatic Arthritis Clinical Trial

Official title: An Exploration of the Dynamic Interaction Between IL-17, IL-17 Inhibition With (Secukinumab) and Neutrophils in Psoriatic Arthritis in Vitro and ex Vivo With Exploratory Study on the Potential Role of Vitamin D

Status Completed

Clinical Trial Summary

The investigators propose an open label pragmatic clinical and laboratory study designed to investigate, in detail, the clinical and molecular effects of Interleukin 17 (IL-17) and inhibition of IL-17 with secukinumab, on neutrophil function in vitro and ex vivo.

As secondary, exploratory objectives, the investigators will utilise the fact that secukinumab is to be administering to 20 patients with Psoriatic Arthritis (PsA) and investigate whether there is any relationship between vitamin D status and response to secukinumab, with respect to efficacy and adverse events. The results of this secondary exploratory analysis will inform the design of a larger, definitive study.

Clinical Trial Description

Phase: Phase 2 Clinical Trial of an Investigational Medicinal Product (CTIMP)

Sample Size: 20 patients plus 10 healthy controls are to be enrolled in total.

Study Population:

Patient treatment group: 20 patients with active psoriatic arthritis (fulfilling Classification Criteria for Psoriatic Arthritis [CASPAR] criteria) affecting ≥2 peripheral joints (swollen and tender) that have not responded to at least one standard Disease-modifying antirheumatic drugs (DMARDs).

Healthy control group: 10 healthy control blood samples (matched for gender to the patients and within 5 years of mean age within each gender subgroup).

Number of Sites: 1 - Rheumatology clinic at Aintree University Hospital, Liverpool

Study Duration: 24 months in total with 12 months of therapy, and 12 months for staggered enrolment and laboratory investigations

Description of Agent/Intervention

Secukinumab 150mg/300mg subcutaneous injection once weekly for the first 4 weeks then 150mg subcutaneous injection 4 weekly for up to 11 months.

Primary Aim:

The primary aim is to determine the molecular effects of IL-17 and inhibition of IL-17 with secukinumab on neutrophil phenotype, lifespan, function and production of IL-17.

Secondary Aims:

1. To determine if neutrophil life span and function is associated with vitamin D concentration and VDR receptor expression in PsA patients, and

2. To explore whether vitamin D concentrations and VDR expression influence neutrophil lifespan and function in PsA patients before and after treatment with secukinumab.

Exploratory Aims:

1. To evaluate the clinical response of patients with psoriatic arthritis, treated with secukinumab using Psoriasis Area and Severity Index (PASI 75) and American College of Rheumatology response criteria (ACR20),

2. To identify whether vitamin D status according to winter or summer seasons and levels of VDR expression are associated with skin and joint responses or infection in patients treated with secukinumab in PsA, assessed using PASI 75 and 90, ACR20 response and reporting of infection adverse events.

3. To evaluate the safety of patients treated with secukinumab in terms of adverse events (AE), serious adverse events (SAE), infections and serious infections, malignancies, acute injection site reactions and potential immunogenicity over 12 months.

Study Design:

Screening for eligibility

Patient group: Patients attending routine rheumatology assessments will be screened for suitability for the study. Eligible patients, based on diagnosis of PsA (meeting CASPAR criteria and with peripheral joint involvement), will be approached to determine if they are willing to participate.

Eligible patients will be registered into the study and will receive secukinumab treatment in addition to their standard DMARD treatment.

Healthy Control Group: Healthy controls matched by gender and within 5 years of mean patient age (assessed in patient group) will be recruited from National health Service (NHS) and university staff.

Baseline assessment:

Baseline assessment of Vitamin D, VDR, Neutrophil function ACR20, Body Surface Area (BSA), PASI 75 and 90, Nail Psoriasis Severity Index (NAPSI), Psoriatic Arthritis Response Criteria (PSARC), EuroQol five dimensions questionnaire (EQ5D) & Health Assessment Questionnaire (HAQ).

1. Secukinumab group

3 months - assessment of Vitamin D, VDR, Neutrophil function, ACR20, PASI 75 AND 90, NAPSI, PSARC, EQ5D, HAQ

6 months - assessment of Vitamin D, VDR, Neutrophil function, ACR20, PASI 75 AND 90, NAPSI, PSARC, EQ5D, HAQ

9 months - assessment of Vitamin D, VDR , ACR20, PASI 75 AND 90, NAPSI, PSARC, EQ5D HAQ

12 months - assessment of Vitamin D, VDR, Neutrophil function, ACR20, PASI 75 AND 90, NAPSI, PSARC, EQ5D, HAQ

13 months (final follow up visit) - pregnancy test, Full Blood Count (FBC), LFTs, serum creatinine and body temperature measurement.

Then exit study

2. Healthy Control Group: Blood sample obtained at baseline for assessment of Vitamin D, VDR and neutrophil function.

Analysis Plan:

Phase 1:

• Measure change at 3 month, 6 and 12 months assessments (from baseline) in neutrophil function, in the secukinumab group.

Phase 2:

• Measure vitamin D concentration, VDR at 3 months, 6 months, 9 months and 12 months.

• Model fluctuation in vitamin D, which is season dependant and estimate when it is maximal.

• Compare treatment response at time point treatment with lowest vitamin D concentration (winter time) with that with highest vitamin D concentration (summer time).

• Assess whether difference in neutrophil function, ACR20, PASI 75 and 90 response and NAPSI correlate with change in vitamin D, using longitudinal models ;

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Psoriatic
• Psoriatic Arthritis

• NCT number: NCT02854163
• Study type: Interventional
• Source: University of Liverpool
• Status: Completed
• Phase: Phase 2
• Start date: October 15, 2016
• Completion date: September 18, 2019