Clinical trial NCT01866592: Vascular Inflammation in Psoriasis - Extension Study
Official title: Vascular Inflammation in Psoriasis - Extension Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Psoriasis
Cardiovascular Disease
Keywords: Psoriasis
Cardiovascular Disease
Vascular Inflammation
Lipid Biomarkers
Metabolic biomarkers
FDG-PET/CT
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: AbbVie
First posted: 2013-05-31
Enrollment: 81
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Males and females 18 years of age and older.
2. Subject completed the VIP Study
3. 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
4. Subject is willing and able to avoid topical or systemic prescription treatments for psoriasis besides adalimumab during the course of the study
5. Women are eligible to participate in the study if they meet one of the following criteria:

   1. 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.
   2. Women who have undergone tubal ligation
   3. Women who are postmenopausal (for at least one year), sterile, or hysterectomized are eligible to participate
   4. 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.
6. 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.
7. Able and willing to give written informed consent and to comply with requirements of this study protocol.

Exclusion Criteria:

1. Previous adverse event following exposure to a TNF-alpha antagonist that led to discontinuation of the TNF inhibitor and contraindicates future treatment.
2. Previous lack of response to a TNF-alpha antagonist led to discontinuation.
3. Diagnosis of erythrodermic psoriasis, generalized pustular psoriasis, or medication-induced or medication-exacerbated psoriasis.
4. Diagnosis of other active skin diseases or skin infections (bacterial, fungal, or viral) that may interfere with evaluation of psoriasis.
5. Subject is taking or requires oral or injectable corticosteroids during the study. Inhaled corticosteroids for stable medical conditions are allowed.
6. 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.
7. 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%)
8. Uncontrolled hypertension, with measured systolic blood pressure \>180 mmHg or diastolic blood pressure \>90 mmHg
9. History of demyelinating diseases or lupus.
10. 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.
11. 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.
12. Female subject who is pregnant or breast-feeding or considering becoming pregnant during the study.
13. 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)
14. Recent history of substance abuse or psychiatric illness that could preclude compliance with the protocol.
15. 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.

Primary outcomes:
measure: Change in Vascular Inflammation
timeFrame: 52 weeks (continuation group) or 64 weeks (crossover group)
measure: Change in Vascular Inflammation
timeFrame: 52 weeks of adalimumab treatment
measure: Change in Cardiometabolic Biomarker - Total Cholesterol
timeFrame: 52 weeks (continuation group) or 64 weeks (crossover group)
measure: Change in Cardiometabolic Biomarker - Cholesterol Efflux
timeFrame: 52 weeks (continuation group) or 64 weeks (crossover group)
measure: Change in Cardiometabolic Biomarker - Low-density Lipoprotein Particle
timeFrame: 52 weeks (continuation group) or 64 weeks (crossover group)
measure: Change in Cardiometabolic Biomarker - High-density Lipoprotein Particle
timeFrame: 52 weeks (continuation group) or 64 weeks (crossover group)
measure: Change in Cardiometabolic Biomarker - Log Insulin
timeFrame: 52 weeks (continuation group) or 64 weeks (crossover group)
measure: Change in Cardiometabolic Biomarker - Log Adiponectin
timeFrame: 52 weeks (continuation group) or 64 weeks (crossover group)
measure: Change in Cardiometabolic Biomarker - Log Leptin
timeFrame: 52 weeks (continuation group) or 64 weeks (crossover group)
measure: Change in Cardiometabolic Biomarker - Log C-reactive Protein
timeFrame: 52 weeks (continuation group) or 64 weeks (crossover group)
measure: Change in Cardiometabolic Biomarker - Log Tumor Necrosis Factor-Alpha
timeFrame: 52 weeks (continuation group) or 64 weeks (crossover group)
measure: Change in Cardiometabolic Biomarker - Log Interleukin 6
timeFrame: 52 weeks (continuation group) or 64 weeks (crossover group)
measure: Change in Cardiometabolic Biomarker - GlycA
timeFrame: 52 weeks (continuation group) or 64 weeks (crossover group)
measure: Change in Cardiometabolic Biomarkers: - Total Cholesterol
timeFrame: 52 weeks of adalimumab treatment
measure: Change in Cardiometabolic Biomarker - Cholesterol Efflux
timeFrame: 52 weeks of adalimumab treatment
measure: Change in Cardiometabolic Biomarker - Low-density Lipoprotein Particle
timeFrame: 52 weeks of adalimumab treatment
measure: Change in Cardiometabolic Biomarker - High-density Lipoprotein Particle
timeFrame: 52 weeks of adalimumab treatment
measure: Change in Cardiometabolic Biomarker - Log Insulin
timeFrame: 52 weeks of adalimumab treatment
measure: Change in Cardiometabolic Biomarker - Log Adiponectin
timeFrame: 52 weeks of adalimumab treatment
measure: Change in Cardiometabolic Biomarker - Log Leptin
timeFrame: 52 weeks of adalimumab treatment
measure: Change in Cardiometabolic Biomarker - Log C-reactive Protein
timeFrame: 52 weeks of adalimumab treatment
measure: Change in Cardiometabolic Biomarker - Log Tumor Necrosis Factor-Alpha
timeFrame: 52 weeks of adalimumab treatment
measure: Change in Cardiometabolic Biomarker - Log Interleukin 6
timeFrame: 52 weeks of adalimumab treatment
measure: Change in Cardiometabolic Biomarker - GlycA
timeFrame: 52 weeks of adalimumab treatment
Secondary outcomes:
measure: Psoriasis Activity (PASI and PGA)
timeFrame: 52 weeks (continuation group) or 64 weeks (crossover group)
measure: Safety/Adverse Events
timeFrame: Baseline - Week 52
measure: Change in Patient-Reported Quality of Life Outcomes-EuroQol EQ-5D
timeFrame: 52 weeks (continuation group) or 64 weeks (crossover group)
measure: Change in Patient-Reported Quality of Life Outcomes - Dermatology Life Quality Index (DLQI)
timeFrame: 52 weeks (continuation group) or 64 weeks (crossover group)
measure: Change in Patient-Reported Quality of Life Outcomes - MEDFICTS Dietary Assessment
timeFrame: 52 weeks (continuation group) or 64 weeks (crossover group)
measure: Change in Patient-Reported Quality of Life Outcomes - International Physical Activity Questionnaire (IPAQ)
timeFrame: 52 weeks (continuation group) or 64 weeks (crossover group)
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: University of California, Davis Health System
state: California
city: Denver
country: United States
facility: University of Colorado
state: Colorado
city: Bethesda
country: United States
facility: National Heart, Lung, and Blood Institute
state: Maryland
city: Buffalo
country: United States
facility: Buffalo Medical Group
state: New York
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Dallas
country: United States
facility: Menter Dermatology Research Institute
state: Texas
city: Houston
country: United States
facility: Center for Clinical Studies
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: University of Pennsylvania
name: Joel M Gelfand, MD MSCE
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.