Vascular Inflammation in Psoriasis - Extension Study

NCT01866592 | Completed Phase 4 Results DMC

• 1 other identifier: 817552
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 9

Brief Summary

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.

Conditions

Psoriasis; Cardiovascular Disease

Keywords

Psoriasis; Cardiovascular Disease; Vascular Inflammation; Lipid Biomarkers; Metabolic biomarkers; FDG-PET/CT

Outcome Measures

Primary Outcomes (24)

• 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 Outcomes (6)

• Psoriasis Activity (PASI and PGA)

  52 weeks (continuation group) or 64 weeks (crossover group)

• Safety/Adverse Events

  Baseline - Week 52

• Change in Patient-Reported Quality of Life Outcomes-EuroQol EQ-5D

  52 weeks (continuation group) or 64 weeks (crossover group)

• Change in Patient-Reported Quality of Life Outcomes - Dermatology Life Quality Index (DLQI)

  52 weeks (continuation group) or 64 weeks (crossover group)

• Change in Patient-Reported Quality of Life Outcomes - MEDFICTS Dietary Assessment

  52 weeks (continuation group) or 64 weeks (crossover group)

Study Arms (1)

Single-Arm, open-label extension trial

OTHER

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

Interventions

Adalimumab DRUG

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.

Also known as: Humira

Single-Arm, open-label extension trial

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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;

Sponsors & Collaborators

• University of Pennsylvania: lead
• AbbVie: collaborator

Study Sites (9)

University of California, Davis Health System

Sacramento, California, 95816, United States

Location

University of Colorado

Denver, Colorado, 80045, United States

Location

National Heart, Lung, and Blood Institute

Bethesda, Maryland, 20892, United States

Location

Buffalo Medical Group

Buffalo, New York, 14221, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Menter Dermatology Research Institute

Dallas, Texas, 75246, United States

Location

Center for Clinical Studies

Houston, Texas, 77004, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Related Publications (1)

• Mehta NN, Shin DB, Joshi AA, Dey AK, Armstrong AW, Duffin KC, Fuxench ZC, Harrington CL, Hubbard RA, Kalb RE, Menter A, Rader DJ, Reilly MP, Simpson EL, Takeshita J, Torigian DA, Werner TJ, Troxel AB, Tyring SK, Vanderbeek SB, Van Voorhees AS, Playford MP, Ahlman MA, Alavi A, Gelfand JM. Effect of 2 Psoriasis Treatments on Vascular Inflammation and Novel Inflammatory Cardiovascular Biomarkers: A Randomized Placebo-Controlled Trial. Circ Cardiovasc Imaging. 2018 Jun;11(6):e007394. doi: 10.1161/CIRCIMAGING.117.007394.

  PMID: 29776990 DERIVED

MeSH Terms

Conditions

Psoriasis; Cardiovascular Diseases

Interventions

Adalimumab

Condition Hierarchy (Ancestors)

Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Suzette Baez VanderBeek, MPH
• Organization: University of Pennsylvania

suzette.baezvanderbeek@uphs.upenn.edu

2156623514

Study Officials

• Joel M Gelfand, MD MSCE

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2013
• First Posted: May 31, 2013
• Study Start: April 1, 2013
• Primary Completion: August 8, 2016
• Study Completion: October 27, 2016
• Last Updated: May 22, 2018
• Results First Posted: May 22, 2018

Record last verified: 2018-04

Locations

US (9)