Vascular Inflammation in Psoriasis Trial (VIP)

Overview

Status: Recruiting
Keywords: psoriasis , inflammation
IRB Number: 00056453
Specialty: Dermatology
Sub Specialties: Psoriasis and Phototherapy

Brief Summary

Study Objectives

Primary objectives

  • To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on
    • Vascular inflammation as measured by FDG-PET/CT
    • Cardiometabolic biomarkers, including lipoprotein levels, particles and function, as well as metabolic and inflammatory-based measures

 

Secondary objectives

  • To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on
    • Psoriasis activity and severity
    • Safety
    • Patient-reported outcomes such as quality-of-life measures

Principal Investigator: Kristina Duffin
Department: Dermatology
Co Investigator: Kristina Duffin
Co Investigator: Gerald Krueger

Contact Information

Name:Sasha Hamel
Phone: 8012132726
Email: sasha.hamel@gmail.com

Inclusion Criteria

 

Inclusion Criteria

    1. Males and females 18 years of age and older.
    2. Clinical diagnosis of psoriasis for at least 6 months as determined by subject interview of his/her medical history and confirmation of diagnosis through physical examination by Investigator.
    3. Stable plaque psoriasis for at least 2 months before Screening and at Baseline (Week 0) as determined by subject interview of his/her medical history.
    4. Moderate to severe psoriasis defined by ≥ 10 percent Body Surface Area (BSA) involvement at the Baseline (Week 0) visit.
    5. PASI score of ≥ 12 at the Baseline (Week 0) visit.
    6. Subject is a candidate for systemic therapy or phototherapy and has active psoriasis despite prior treatment with topical agents.
    7. Women are eligible to participate in the study if they meet one of the following criteria:
      1. Women of childbearing potential must undergo monthly pregnancy testing during the study and agree to use one of the following methods of contraception throughout the duration of the study:
  1. i.    Oral contraceptives;

    ii.    Transdermal contraceptives

    iii.    Injectable or implantable methods

    iv.    Intrauterine devices

    v.    Barrier methods (for example but not limited to a diaphragm with spermicide, condom with spermicide); or

    vi.    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 study baseline visit.

    1. Women who are postmenopausal (for at least one year), sterile, or hysterectomized;
    2. Women who have undergone tubal ligation will be required to undergo monthly pregnancy testing.
    3. Women who agree to be sexually abstinent, defined as total abstinence from sexual intercourse, is considered an adequate form of contraception.  (Agreement to comply with sexual abstinence must be recorded in the source document.)

          8. Subject is judged to be in good general health as determined by the Principal Investigator based upon the results of medical history, laboratory profile, physical examination, and 12-lead electrocardiogram (ECG) performed at screening.

           9. Able and willing to give written informed consent and to comply with requirements of this study protocol.

Exclusion Criteria

 

Exclusion Criteria

Subjects meeting any of the following criteria will be excluded from the study:

  1. Previous adverse event following exposure to a TNF-alpha antagonist and/or UV phototherapy that led to discontinuation of either of these therapies and contraindicates future treatment.
  2. Previous lack of response to a TNF-alpha antagonist and/or UV phototherapy that led to discontinuation of either of these therapies.
  3. Diagnosis of erythrodermic psoriasis, generalized or localized pustular psoriasis, medication-induced or medication-exacerbated psoriasis, or new onset guttate psoriasis.
  4. Diagnosis of other active skin diseases or skin infections (bacterial, fungal, or viral) that may interfere with evaluation of psoriasis.
  5. Cannot avoid UVB phototherapy for at least 14 days prior to the Baseline (Week 0) visit.
  6. Cannot avoid psoralen-UVA phototherapy for at least 30 days prior to the Baseline (Week 0) visit and during the study.
  7. Cannot discontinue systemic therapies for the treatment of psoriasis, or systemic therapies known to improve psoriasis, during the study:
    • Systemic (investigational or marketed) therapies must be discontinued at least 30 days prior to the Baseline (Week 0) visit except for biologics.
      • All biologics, except ustekinumab, must be discontinued for at least 90 days prior to Baseline (Week 0).
      • The IL-12/IL-23 antagonist ustekinumab (half-life of 45.6 ± 80.2 days) must be discontinued for at least 180 days prior to Baseline (Week 0).
    • Investigational agents must be discontinued at least 30 days or 5 half-lives (whichever is longer) prior to the Baseline (Week 0) visit.
  8. Subject is taking or requires oral or injectable corticosteroids during the study.  Inhaled corticosteroids for stable medical conditions are allowed. 
  9. 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.
  10. History of diabetes mellitus, type 1 or type 2- note that patients with type 2 diabetes may be enrolled if the duration of diabetes is <10 years and HbA1c is <7.0%)
  11. Uncontrolled hypertension, with measured systolic blood pressure >180 mmHg or diastolic blood pressure >90 mmHg
  12. History of demyelinating diseases or lupus.
  13. Subject has infection or risk factors for severe infections, for example:
    • Positive serology or 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; 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 has received vaccination with Bacille Calmette-Guerin (BCG) within 365 days prior to Screening;
    • Subject has received vaccination with a live viral agent 30 days prior to Screening or will require a live vaccination during study participation including up to 30 days after the last dose of study drug.
  14. 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.
  15. Female subject who is pregnant or breast-feeding or considering becoming pregnant during the study.
  16. Screening clinical 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); or
  17. Recent history of substance abuse or psychiatric illness that could preclude compliance with the protocol.
  18. History of any substance abuse within 365 days of screening visit
  19. Alcohol use >14 drinks per week at the screening visit or within 30 days of the screening period
  20. If subject is on cholesterol-lowering medication (e.g. statin), dose and form of medication must be stable for 90 days prior to week 0 and remain stable throughout the duration of the study.
  21. History of photosensitivity of medical condition that may be exacerbated by UV exposures such as lupus or dermatomyositis

 

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