NCT02854163已完成2 期
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
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Change from baseline in neutrophil apoptosis in PsA patients treated with Secukinumab at 12 months
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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.
- •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).
- •History of hypersensitivity to the study drug or its excipients or to drugs of similar classes.
- •Previous treatment with any cell-depleting therapies including but not limited to anti-CD20 investigational agents (e.g. CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19).
- •Active ongoing inflammatory diseases other than PsA that might confound the evaluation of the benefit of secukinumab therapy.
- •Underlying metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine,cardiac, infectious or gastrointestinal conditions which in the opinion of the Investigator immunocompromise the patient and/or place the patient at unacceptable risk for participation in an immunomodulatory therapy.
- •Significant medical problems or diseases, including but not limited to the following: uncontrolled hypertension (≥ 160/95 mmHg), congestive heart failure (New York Heart Association status of class III or IV), uncontrolled diabetes.
- •History of clinically significant liver disease or liver injury as indicated by abnormal liver function tests (LFT) such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, or serum bilirubin. The Investigator should be guided by the following criteria:
- •Any single parameter may not exceed 2 x upper limit of normal (ULN). A single parameter elevated up to and including 2 x ULN should be re-checked once more as soon as possible, and in all cases, at least prior to enrollment/registration, to rule out laboratory error.
- •If the total bilirubin concentration is increased above 2 x ULN, total bilirubin should be differentiated into the direct and indirect reacting bilirubin. In any case, serum bilirubin should not exceed 1.6 mg/dL (27 μmol/L).
- •History of renal trauma, glomerulonephritis, or patients with 1 kidney only, or a serum creatinine level exceeding 1.5 mg/dL (132.6 μmol/L).
- •Screening total white blood cell (WBC) count < 3 000/μL, or platelets < 100 000/μL or neutrophils < 1 500/μL or hemoglobin < 8.5 g/dL (85 g/L).
- •Active systemic infections during the last 2 weeks (exception: common cold) prior to registration.
- •History of ongoing, chronic or recurrent infectious disease or evidence of tuberculosis according to local practice/guidelines) or a positive QuantiFERON TB-Gold test or TB-Spot Test (as indicated in Section 4.1 and Table 6-1). Patients with a positive test may participate in the study if further work up (according to local practice/guidelines) establishes conclusively that the patient has no evidence of active tuberculosis. If presence of latent tuberculosis is established then treatment according to local country guidelines must have been initiated.
- •Known infection with human immunodeficiency virus, hepatitis B or hepatitis C at Screening or registration.
- •History of lymphoproliferative disease or any known malignancy or history of malignancy of any organ system within the past 5 years (except for basal cell carcinoma or actinic keratoses that have been treated with no evidence of recurrence in the past 3 months, carcinoma in situ of the cervix or non-invasive malignant colon polyps that have been removed).
- •Use of Vitamin D containing supplements.
- •Inability or unwillingness to undergo repeated venepuncture (e.g. because of poor tolerability or lack of access to veins).
- •Patients who have received a live vaccine within 4 weeks prior to planned registration must be excluded.
- •Healthy Controls Inclusion Criteria:
- •10 healthy control blood samples.
- •The healthy controls will be recruited from staff at the University of Liverpool or Aintree University hospitals and who are not taking nor have taken over the preceding 6 months, any immunosuppressive agent including systemic corticosteroids and whose health is otherwise good. There will be an equal balance of males to females. Matching to biologic or DMARD controls is not required. The healthy controls will provide one sample of blood for neutrophil studies.
研究组 & 干预措施
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.
干预措施: Secukinumab (Drug)
结局指标
主要结局
Change from baseline in neutrophil apoptosis in PsA patients treated with Secukinumab at 12 months
时间窗: 12 months
Neutrophil apoptosis will be measured using flow-cytometry.
Change from baseline in neutrophil receptor expression in PsA patients treated with Secukinumab at 12 months
时间窗: 12 months
Neutrophil phenotype will be determine as percent of receptor expressing cells assessed by flow cytometry
次要结局
- Clinical response of of psoriatic Nail involvement (NAPSI) to treatment at 12 months(12 months)
- Number of patients with treatment-related adverse events as assessed by MedDRA(12 months)
- Number of patients with treatment-related serious adverse events as assessed by MedDRA(12 months)
- 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)
- Clinical response of psoriatic skin rash (PASI75) to treatment 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)
- Change from baseline in quality of life in PsA patients treated with Secukinumab at 12 months using HAQ questionnaire(12 months assessments from baseline)
- Change from baseline in quality of life in PsA patients treated with Secukinumab at 12 months using EQ5D questionnaire(12 months assessments from baseline)
- Clinical response of psoriatic arthritis (ARC20) to treatment at 12 months(12 months)
研究者
Robert J Moots
Professor of Rheumatology
University of Liverpool
研究点 (1)
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