Vascular Inflammation in Psoriasis - Extension Study

Study Overview
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Brief Summary
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VIP-E is a one-arm, open-label, 40-52 week extension study to continue or cross over subjects of the VIP study (# 814278) to active drug (adalimumab) to determine if there is sustained improvement in vascular inflammation, lipid metabolism, and inflammatory markers. VIP-E extends VIP study procedures for 40-52 weeks including questionnaires, physical exams, blood and urine samples, lab tests, one additional FDG-PET/CT scan, and adalimumab injections following FDA-approved psoriasis treatment regimen.

Official Title
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Vascular Inflammation in Psoriasis - Extension Study

Conditions
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Psoriasis, Cardiovascular Disease

Intervention / Treatment
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* Drug: Adalimumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females 18 years of age and older. Subject completed the VIP Study Subject willing and able to avoid prolonged exposure of skin affected by psoriasis to natural or sunlight or tanning beds during the course of the study Subject is willing and able to avoid topical or systemic prescription treatments for psoriasis besides adalimumab during the course of the study Women are eligible to participate in the study if they meet one of the following criteria: Women of childbearing potential must undergo pregnancy testing during the baseline visit and agree to use one of the following methods of contraception throughout the 13-month study: Oral contraceptives; Transdermal contraceptives Injectable or implantable methods Intrauterine devices Barrier methods (for example but not limited to a diaphragm with spermicide, condom with spermicide); or Vasectomized partner Subjects using oral or parental forms of contraceptives must have been using those methods of birth control for at least three months prior to the baseline visit. Women who have undergone tubal ligation Women who are postmenopausal (for at least one year), sterile, or hysterectomized are eligible to participate Women who agree to be sexually abstinent, defined as total abstinence from sexual intercourse, as a form of contraception are eligible to participate in the study. Subject is judged to be in good general health as determined by the Principal Investigator based upon the results of medical history, laboratory profile, and physical examination. Able and willing to give written informed consent and to comply with requirements of this study protocol. Exclusion Criteria: Previous adverse event following exposure to a TNF-alpha antagonist that led to discontinuation of the TNF inhibitor and contraindicates future treatment. Previous lack of response to a TNF-alpha antagonist led to discontinuation. Diagnosis of erythrodermic psoriasis, generalized pustular psoriasis, or medication-induced or medication-exacerbated psoriasis. Diagnosis of other active skin diseases or skin infections (bacterial, fungal, or viral) that may interfere with evaluation of psoriasis. Subject is taking or requires oral or injectable corticosteroids during the study. Inhaled corticosteroids for stable medical conditions are allowed. Poorly controlled medical condition, such as unstable ischemic heart disease, congestive heart failure, recent cerebrovascular accidents, psychiatric disease requiring frequent hospitalization, and any other condition, which, in the opinion of the Investigator, would put the subject at risk by participation in the study. History of diabetes mellitus, type 1 or type 2 (patients with type 2 diabetes may be enrolled if the duration of diabetes is <10 years and HbA1c is <7.0%) Uncontrolled hypertension, with measured systolic blood pressure >180 mmHg or diastolic blood pressure >90 mmHg History of demyelinating diseases or lupus. Subject has infection or risk factors for severe infections, for example: Known history of HIV, hepatitis B or C, or other severe, recurrent, or persistent infections; Excessive immunosuppression or other factors associated with it, including human immunodeficiency virus infection; Active tuberculosis (TB) disease; Evidence of latent TB infection demonstrated by Purified Protein Derivative (PPD) ≥ 5 mm of induration or positive Quantiferon-GOLD results as determined within 6 months of the baseline visit for VIP-E; except if prophylactic treatment for TB, as recommended by local guidelines, is initiated prior to administration of study drug or if there is documentation that the subject has received prophylactic treatment for TB previously. Any other significant infection requiring hospitalization or intravenous (IV) antibiotics in the month prior to Baseline; Infection requiring treatment with oral or parenteral antibiotics within 14 days prior to Baseline; Subject will require a live vaccination during study participation including up to 30 days after the last dose of study drug. Subject has history of hematological or solid malignancy within the past five years other than successfully treated basal cell carcinoma, non-metastatic cutaneous squamous cell carcinoma or cervical carcinoma in situ. Female subject who is pregnant or breast-feeding or considering becoming pregnant during the study. Clinic laboratory analyses showing any of the following abnormal results: Hemoglobin (Hgb) < 10 g/dL in females or <12 g/dL in males; White blood cell (WBC) count <2.5 x 109/L Subject can be included if WBC count is <2.5 x x 109/L and absolute neutrophil count (ANC) is >1000 cells / mm3. WBC count > 15 x 109/L; Platelet count < 100 x 109/L; Serum aspartate transaminase (AST) or alanine transaminase (ALT) >2.5 upper limits of normal (ULN); Serum total bilirubin ≥2 mg/dL (≥26 µmol/L) Recent history of substance abuse or psychiatric illness that could preclude compliance with the protocol. If subject is on cholesterol-lowering medication (e.g. statin), dose and form of medication must be stable for 90 days prior to baseline and remain stable throughout the duration of the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Single-Arm, open-label extension trial<br>Single-arm, open label extension trial to continue treatment with Humira (Adalimumab) subcutaneous injection 80mg initial dose followed by 40mg maintenance dose every other week for up to 52 weeks. | Drug: Adalimumab<br>* Study participants will receive the FDA-approved dosing schedule for Adalimumab (Humira): an initial dose of 80mg followed by a 40mg maintenance dose every other week up to 52 weeks.<br>* Other names: Humira;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Vascular Inflammation | Change in total vascular inflammation of five aortic segments as assessed on FDG-PET/CT between week 52 of the adalimumab treatment period and baseline scans (prior to randomization in the VIP Trial). The arterial uptake of FDG is measured by the standardized uptake value (SUV) max divided by the venous SUIV mean yielding a target to background ration (TBR). If subjects were randomized to adalimumab in the VIP Trial, the time frame is a total of 52 weeks (continuation group). If subjects were randomized to placebo or phototherapy in the VIP Trial, additional 12 weeks added to the time frame for a total of 64 weeks (crossover group). | 52 weeks (continuation group) or 64 weeks (crossover group) | 
| Change in Vascular Inflammation | Change in total vascular inflammation of five aortic segments as assessed on FDG-PET/CT between week 52 of the adalimumab treatment period and start of adalimumab.The arterial uptake of FDG is measured by the standardized uptake value (SUV) max divided by the venous SUIV mean yielding a target to background ration (TBR). | 52 weeks of adalimumab treatment | 
| Change in Cardiometabolic Biomarker - Total Cholesterol | Change in metabolic, lipid, and inflammatory biomarker levels between week 52 of the adalimumab treatment period and baseline assessments from the VIP trial - Total Cholesterol. If subjects were randomized to adalimumab in the VIP Trial, the time frame is a total of 52 weeks (continuation group). If subjects were randomized to placebo or phototherapy in the VIP Trial, additional 12 weeks added to the time frame for a total of 64 weeks (crossover group). | 52 weeks (continuation group) or 64 weeks (crossover group) | 
| Change in Cardiometabolic Biomarker - Cholesterol Efflux | The ability to promote cholesterol efflux from macrophages is a classic function of HDL that is thought to be an important mechanism by which HDL protects against atherosclerosis. HDL cholesterol efflux capacity assays are performed based on published methods using J774 cells derived from a murine macrophage cell line (Mehta NN Atherosclerosis 2012). Efflux is calculated as a unitless measure by using the following formula: [(µCi of 3H-cholesterol in media containing apoB-depleted subject plasma - µCi of 3H-cholesterol in plasma-free media) / (µCi of 3H-cholesterol in media containing apoB-depleted pooled control plasma-µCi of 3H-cholesterol in pooled control plasma-free media)]. If subjects were randomized to adalimumab in the VIP Trial, the time frame is a total of 52 weeks (continuation group). If subjects were randomized to placebo or phototherapy in the VIP Trial, additional 12 weeks added to the time frame for a total of 64 weeks (crossover group). | 52 weeks (continuation group) or 64 weeks (crossover group) | 
| Change in Cardiometabolic Biomarker - Low-density Lipoprotein Particle | Change in metabolic, lipid, and inflammatory biomarker levels between week 52 of the adalimumab treatment period and baseline assessments from the VIP trial - Low-density lipoprotein particle If subjects were randomized to adalimumab in the VIP Trial, the time frame is a total of 52 weeks (continuation group). If subjects were randomized to placebo or phototherapy in the VIP Trial, additional 12 weeks added to the time frame for a total of 64 weeks (crossover group). | 52 weeks (continuation group) or 64 weeks (crossover group) | 
| Change in Cardiometabolic Biomarker - High-density Lipoprotein Particle | Change in metabolic, lipid, and inflammatory biomarker levels between week 52 of the adalimumab treatment period and baseline assessments from the VIP trial - High-density lipoprotein particle If subjects were randomized to adalimumab in the VIP Trial, the time frame is a total of 52 weeks (continuation group). If subjects were randomized to placebo or phototherapy in the VIP Trial, additional 12 weeks added to the time frame for a total of 64 weeks (crossover group). | 52 weeks (continuation group) or 64 weeks (crossover group) | 
| Change in Cardiometabolic Biomarker - Log Insulin | Change in metabolic, lipid, and inflammatory biomarker levels between week 52 of the adalimumab treatment period and baseline assessments from the VIP trial - Log Insulin If subjects were randomized to adalimumab in the VIP Trial, the time frame is a total of 52 weeks (continuation group). If subjects were randomized to placebo or phototherapy in the VIP Trial, additional 12 weeks added to the time frame for a total of 64 weeks (crossover group). | 52 weeks (continuation group) or 64 weeks (crossover group) | 
| Change in Cardiometabolic Biomarker - Log Adiponectin | Change in metabolic, lipid, and inflammatory biomarker levels between week 52 of the adalimumab treatment period and baseline assessments from the VIP trial - Log Adiponectin If subjects were randomized to adalimumab in the VIP Trial, the time frame is a total of 52 weeks (continuation group). If subjects were randomized to placebo or phototherapy in the VIP Trial, additional 12 weeks added to the time frame for a total of 64 weeks (crossover group). | 52 weeks (continuation group) or 64 weeks (crossover group) | 
| Change in Cardiometabolic Biomarker - Log Leptin | Change in metabolic, lipid, and inflammatory biomarker levels between week 52 of the adalimumab treatment period and baseline assessments from the VIP trial - Log Leptin If subjects were randomized to adalimumab in the VIP Trial, the time frame is a total of 52 weeks (continuation group). If subjects were randomized to placebo or phototherapy in the VIP Trial, additional 12 weeks added to the time frame for a total of 64 weeks (crossover group). | 52 weeks (continuation group) or 64 weeks (crossover group) | 
| Change in Cardiometabolic Biomarker - Log C-reactive Protein | Change in metabolic, lipid, and inflammatory biomarker levels between week 52 of the adalimumab treatment period and baseline assessments from the VIP trial - Log C-reactive protein If subjects were randomized to adalimumab in the VIP Trial, the time frame is a total of 52 weeks (continuation group). If subjects were randomized to placebo or phototherapy in the VIP Trial, additional 12 weeks added to the time frame for a total of 64 weeks (crossover group). | 52 weeks (continuation group) or 64 weeks (crossover group) | 
| Change in Cardiometabolic Biomarker - Log Tumor Necrosis Factor-Alpha | Change in metabolic, lipid, and inflammatory biomarker levels between week 52 of the adalimumab treatment period and baseline assessments from the VIP trial - Log Tumor Necrosis Factor-Alpha If subjects were randomized to adalimumab in the VIP Trial, the time frame is a total of 52 weeks (continuation group). If subjects were randomized to placebo or phototherapy in the VIP Trial, additional 12 weeks added to the time frame for a total of 64 weeks (crossover group). | 52 weeks (continuation group) or 64 weeks (crossover group) | 
| Change in Cardiometabolic Biomarker - Log Interleukin 6 | Change in metabolic, lipid, and inflammatory biomarker levels between week 52 of the adalimumab treatment period and baseline assessments from the VIP trial - Log Interleukin 6 If subjects were randomized to adalimumab in the VIP Trial, the time frame is a total of 52 weeks (continuation group). If subjects were randomized to placebo or phototherapy in the VIP Trial, additional 12 weeks added to the time frame for a total of 64 weeks (crossover group). | 52 weeks (continuation group) or 64 weeks (crossover group) | 
| Change in Cardiometabolic Biomarker - GlycA | Change in metabolic, lipid, and inflammatory biomarker levels between week 52 of the adalimumab treatment period and baseline assessments from the VIP trial - GlycA If subjects were randomized to adalimumab in the VIP Trial, the time frame is a total of 52 weeks (continuation group). If subjects were randomized to placebo or phototherapy in the VIP Trial, additional 12 weeks added to the time frame for a total of 64 weeks (crossover group). | 52 weeks (continuation group) or 64 weeks (crossover group) | 
| Change in Cardiometabolic Biomarkers: - Total Cholesterol | Change in metabolic, lipid, and inflammatory biomarker levels between week 52 of the adalimumab treatment period and the start of adalimumab - Total Cholesterol | 52 weeks of adalimumab treatment | 
| Change in Cardiometabolic Biomarker - Cholesterol Efflux | Change in metabolic, lipid, and inflammatory biomarker levels between week 52 of the adalimumab treatment period and baseline assessments from the VIP trial - Cholesterol Efflux | 52 weeks of adalimumab treatment | 
| Change in Cardiometabolic Biomarker - Low-density Lipoprotein Particle | Change in metabolic, lipid, and inflammatory biomarker levels between week 52 of the adalimumab treatment period and baseline assessments from the VIP trial - Low-density lipoprotein particle | 52 weeks of adalimumab treatment | 
| Change in Cardiometabolic Biomarker - High-density Lipoprotein Particle | Change in metabolic, lipid, and inflammatory biomarker levels between week 52 of the adalimumab treatment period and baseline assessments from the VIP trial - High-density lipoprotein particle | 52 weeks of adalimumab treatment | 
| Change in Cardiometabolic Biomarker - Log Insulin | Change in metabolic, lipid, and inflammatory biomarker levels between week 52 of the adalimumab treatment period and baseline assessments from the VIP trial - Log Insulin | 52 weeks of adalimumab treatment | 
| Change in Cardiometabolic Biomarker - Log Adiponectin | Change in metabolic, lipid, and inflammatory biomarker levels between week 52 of the adalimumab treatment period and baseline assessments from the VIP trial - Log Adiponectin | 52 weeks of adalimumab treatment | 
| Change in Cardiometabolic Biomarker - Log Leptin | Change in metabolic, lipid, and inflammatory biomarker levels between week 52 of the adalimumab treatment period and baseline assessments from the VIP trial - Log Leptin | 52 weeks of adalimumab treatment | 
| Change in Cardiometabolic Biomarker - Log C-reactive Protein | Change in metabolic, lipid, and inflammatory biomarker levels between week 52 of the adalimumab treatment period and baseline assessments from the VIP trial - Log C-reactive protein | 52 weeks of adalimumab treatment | 
| Change in Cardiometabolic Biomarker - Log Tumor Necrosis Factor-Alpha | Change in metabolic, lipid, and inflammatory biomarker levels between week 52 of the adalimumab treatment period and baseline assessments from the VIP trial - Log Tumor Necrosis Factor-Alpha | 52 weeks of adalimumab treatment | 
| Change in Cardiometabolic Biomarker - Log Interleukin 6 | Change in metabolic, lipid, and inflammatory biomarker levels between week 52 of the adalimumab treatment period and baseline assessments from the VIP trial - Log Interleukin 6 | 52 weeks of adalimumab treatment | 
| Change in Cardiometabolic Biomarker - GlycA | Change in metabolic, lipid, and inflammatory biomarker levels between week 52 of the adalimumab treatment period and baseline assessments from the VIP trial - GlycA | 52 weeks of adalimumab treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Psoriasis Activity (PASI and PGA) | Change in psoriasis activity will be assessed using the following standardized measurement tools for psoriasis: Psoriasis Area and Severity Index (PASI) and Physician's Global Assessment (PGA). PASI combines the assessment of the severity of lesions and the area affected into a single score with range 0 (no disease) to 72 maximal disease. The PGA is an average assessment of all psoriatic lesions based on erythema, scale, and induration with score range 0 (no disease/clear) to 5 (maximal disease). If subjects were randomized to adalimumab in the VIP Trial, the time frame is a total of 52 weeks (continuation group). If subjects were randomized to placebo or phototherapy in the VIP Trial, additional 12 weeks added to the time frame for a total of 64 weeks (crossover group). | 52 weeks (continuation group) or 64 weeks (crossover group) | 
| Safety/Adverse Events | Safety will be assessed by evaluating all subject reported adverse events through the duration of the study. | Baseline - Week 52 | 
| Change in Patient-Reported Quality of Life Outcomes-EuroQol EQ-5D | EQ-5D is a standardized instrument developed by the EuroQol Group as a measure of health-related quality of life that can be used in a wide range of health conditions and treatments. The EQ-5D consists of a descriptive system and the EQ VAS. The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression on a scale ranging from 1 (no health state problem) to 3 (extreme health state problems). The EQ VAS records the patient's self-rated health on a vertical visual analogue scale ranging from 0, worst health state, to 100, best health state. A scoring function is used to assign a value (i.e., EQ-5D™ index score) to self-reported health states from a set of population-based preference weights. For the U.S. general population, the possible EQ-5D index scores range from -0.11 to 1.0 where 0.0 = death and 1.0 = perfect health. | 52 weeks (continuation group) or 64 weeks (crossover group) | 
| Change in Patient-Reported Quality of Life Outcomes - Dermatology Life Quality Index (DLQI) | The DLQI is calculated by summing the score of 10 questions regarding impact of skin condition on daily life resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired. If subjects were randomized to adalimumab in the VIP Trial, the time frame is a total of 52 weeks (continuation group). If subjects were randomized to placebo or phototherapy in the VIP Trial, additional 12 weeks added to the time frame for a total of 64 weeks (crossover group). | 52 weeks (continuation group) or 64 weeks (crossover group) | 
| Change in Patient-Reported Quality of Life Outcomes - MEDFICTS Dietary Assessment | Patient reported dietary outcomes will be assessed using MEDFICTS (Meats, Eggs, Dairy, Fried foods, fat In baked goods, Convenience foods, fats added at the Table, and Snacks), a brief dietary assessment instrument. This assessment looks at eight different categories of foods and assigns points by type of food and serving size ranging from 0 points (do not consume that food group) to 21 points (consume food group, largest serving size). Your final score is the total of all points for all food categories. If subjects were randomized to adalimumab in the VIP Trial, the time frame is a total of 52 weeks (continuation group). If subjects were randomized to placebo or phototherapy in the VIP Trial, additional 12 weeks added to the time frame for a total of 64 weeks (crossover group). | 52 weeks (continuation group) or 64 weeks (crossover group) | 
| Change in Patient-Reported Quality of Life Outcomes - International Physical Activity Questionnaire (IPAQ) | IPAQ is an instrument designed primarily for population surveillance of physical activity among adults with activity measured in metabolic equivalent (MET)-minutes per week. Per Office of Disease Prevention and Health Promotion's Physical Activity Guidelines: A range of 500 to 1,000 MET-minutes of activity per week provides substantial [health] benefit, and amounts of activity above this range have even more benefit. Amounts of activity below this range also have some benefit. The dose-response relationship continues even within the range of 500 to 1,000 MET-minutes, in that the health benefits of 1,000 MET-minutes per week are greater than those of 500 MET-minutes per week. If subjects were randomized to adalimumab in the VIP Trial, the time frame is a total of 52 weeks (continuation group). If subjects were randomized to placebo or phototherapy in the VIP Trial, additional 12 weeks added to the time frame for a total of 64 weeks (crossover group). | 52 weeks (continuation group) or 64 weeks (crossover group) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Psoriasis, Cardiovascular Disease, Vascular Inflammation, Lipid Biomarkers, Metabolic biomarkers, FDG-PET/CT