Effect of Secukinumab in the Treatment of Psoriatic Arthritis

NCT02854163 | Completed Phase 2 DMC

• 4 other identifiers: UoL0011452015-004502-42LCTU134CAIN457F2208T
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Psoriatic Arthritis

Keywords

Secukinumab; Neutrophils; Vitamin D

Outcome Measures

Primary Outcomes (2)

• Change from baseline in neutrophil apoptosis in PsA patients treated with Secukinumab at 12 months

  Neutrophil apoptosis will be measured using flow-cytometry.

  12 months

• Change from baseline in neutrophil receptor expression in PsA patients treated with Secukinumab at 12 months

  Neutrophil phenotype will be determine as percent of receptor expressing cells assessed by flow cytometry

  12 months

Secondary Outcomes (12)

• Change from baseline in neutrophil rate of phagocytosis in PsA patients treated with Secukinumab at 12 months

  12 months

• Change from baseline in neutrophil chemotaxis in PsA patients treated with Secukinumab at 12 months

  12 months

• Change from baseline in Vitamin D receptor (VDR) expression in PsA patients treated with Secukinumab at 3 months

  3 months assessments from baseline

• Change from baseline in Vitamin D receptor (VDR) expression in PsA patients treated with Secukinumab at 6 months

  6 months assessments from baseline

• Change from baseline in Vitamin D receptor (VDR) expression in PsA patients treated with Secukinumab at 12 months

  12 months assessments from baseline

Study Arms (1)

Secukinumab

EXPERIMENTAL

Secukinumab will be given to all 20 patients registered (Secukinumab group). All doses will be given subcutaneously using the following schedule: 4 weekly injections of 150 or 300 mg subcutaneous injections depending the severity of skin involvement, followed by 11 monthly subcutaneous injections of 150mg. Patients will continue to use their normal DMARDs treatment.

Drug: Secukinumab

Interventions

Secukinumab DRUG

All eligible patients registered into the study will receive four 150 - 300 mg subcutaneous injections at weekly intervals, followed by regular injections 150mg once a month thereafter for a total of 12 months

Also known as: Cosentyx

Secukinumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with active psoriatic arthritis (fulfilling CASPAR criteria) affecting ≥2 peripheral joints (swollen and tender) that have not responded to at least one standard DMARDs
• All meet CASPAR criteria for diagnosis of PsA,
• Be rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP) negative at screening,
• Have had no prior exposure to biologic therapy,
• Not have received parenteral glucocorticosteroids in the 6 weeks prior to the baseline assessment,
• If taking oral glucocorticoids remain on a stable dose of \<10mg throughout the study with no change in dose in the 6 weeks prior to baseline assessment,
• If taking methotrexate or other DMARDs remain on a stable dose throughout the study and not have changed dose or therapy for 6 weeks prior to the baseline assessment

You may not qualify if:

• Active or chronic infection including mycobacterium tuberculosis, HIV, hepatitis B or C
• Absence of active psoriatic arthritis
• Patients who are starting anti-TNF therapy for treating PsA
• Pregnancy and planning pregnancy
• WOCBP who are unwilling or unable ot use acceptable method to avoid pregnancy for study duration plus timeframe as specified in section 5.2.5.
• Women who are pregnant or breastfeeding
• Sexually active fertile men not using effective birth control if their partners are WOCBP.
• Malignancy
• Chest X-ray or chest MRI with evidence of ongoing infectious or malignant process obtained within 3 months prior to Screening and evaluated by a qualified physician.
• Patients with hyponatraemia and nephrotic syndrome
• Previous exposure to secukinumab or other biologic drug directly targeting IL-17 or IL-17 receptor.
• Use of any investigational drug and/or devices within 4 weeks before registration or a period of 5 half-lives of the investigational drug, whichever is longer.
• Significant comorbidity that, in the opinion of the investigator, would impact on ability to participate
• Any change in the dose of oral glucocorticosteroids or DMARDS in the prior 6 weeks prior to the Baseline visit or use of i.v. intramuscular or intra-articular glucocorticosteroid during the last 6 weeks prior to the enrolment visit.
• Patients who have previously been treated with TNFα inhibitors (investigational or approved).

Sponsors & Collaborators

• University of Liverpool: lead
• Novartis: collaborator

Study Sites (1)

Aintree University Hospitals NHS Foundation Trust

Liverpool, L9 7AL, United Kingdom

Location

MeSH Terms

Conditions

Arthritis, Psoriatic

Interventions

secukinumab

Condition Hierarchy (Ancestors)

Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Arthritis; Joint Diseases; Psoriasis; Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Robert J Moots, MD PhD

  University of Liverpool

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Rheumatology

Study Record Dates

• First Submitted: July 20, 2016
• First Posted: August 3, 2016
• Study Start: October 15, 2016
• Primary Completion: September 18, 2019
• Study Completion: September 18, 2019
• Last Updated: April 9, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: Clinical trial results uploaded to EudraCT 12/03/2020

Locations

GB (1)