Vascular Inflammation in Psoriasis-Ustekinumab (VIP-U)
Condition: Psoriasis; Cardiovascular Disease
MeSH terms: Cardiovascular Diseases; Psoriasis; Inflammation
Intervention: Ustekinumab; Placebo
Intervention MeSH terms: Ustekinumab
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: A hybrid RCT (randomized controlled trial) crossover trial where all patients receive total of 52 weeks of active treatment following an RCT phase of 12 weeks (active treatment or placebo). Patients randomized to active treatment will receive additional 40 weeks of active treatment at end of RCT phase; patients randomized to placebo will receive 52 weeks of active treatment at end of RCT phase. Primary outcomes are assessed at end of the RCT phase (comparison of interventions in change from start of treatment) and at end of 52 weeks of active treatment (change from start of treatment).
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 43.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Psoriasis; Cardiovascular Disease; Vascular Inflammation; Lipid Biomarkers; FDG-PET/CT

Summary:

      The VIP-U Study is a clinical trial designed to investigate the effect of ustekinumab
      (Stelara) and placebo on reducing vascular inflammation and cardiometabolic risk biomarkers
      in patients with moderate to severe psoriasis.

      This study will look for systemic vascular inflammation in study participants with a test
      called FDG PET/CT (fluorodeoxyglucose-positron emission tomography/computed tomography). The
      study will also look for cardiometabolic identifiers (heart disease and metabolic factors) in
      blood samples, including markers of high cholesterol, cholesterol efflux function (the
      ability of cholesterol to move in the body), metabolic factors, and inflammation.

      The study will also examine the effects of ustekinumab compared to placebo on psoriasis
      activity, severity and safety.
    

Eligibility 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 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 who are willing to undergo periodic pregnancy
                  testing during the study and agree to use at least one method of contraception
                  throughout the study duration and for at least 15 weeks after the last dose of
                  the study drug are eligible to participate.

               2. Women who are postmenopausal (for at least one year), sterile, or hysterectomized
                  are eligible to participate.

               3. Women who have undergone tubal ligation 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.

          8. Men are eligible to participate in the study if they meet one of the following
             criteria:

               1. Agree to use a proven birth control method during the study and for at least 15
                  weeks after the last dose of the study drug.

               2. Have a female partner who agrees to use at least one method of contraception
                  throughout the study duration and for at least 15 weeks after the last dose of
                  the study drug.

               3. Have a female partner who is postmenopausal (for at least one year), sterile, or
                  hysterectomized;

               4. Have a female partner who has undergone tubal ligation,

               5. Agree to be sexually abstinent, defined as total abstinence from sexual
                  intercourse, as a form of contraception.

          9. 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.

         10. 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 an IL-12/IL-23 antagonist that led to
             discontinuation of therapy and contraindicates future treatment.

          2. Previous lack of response to an IL-12/IL-23 antagonist that led to discontinuation of
             therapy.

          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 or Excimer laser for at least 14 days prior to the
             Baseline (Week 0) visit and during the study.

          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 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).

                    -  Any IL-12/IL-23 antagonist (e.g., ustekinumab, briakinumab) 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,
             cerebrovascular accident or myocardial infarction within the prior 6 months,
             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 with the exception 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. 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 positive Quantiferon-GOLD result;
                  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 within 3 years prior to
                  the first administration of study agent.

               -  Any other significant infection requiring hospitalization or intravenous (IV)
                  antibiotics in the month prior to Baseline;

               -  Infection requiring treatment with oral or parenteral (other than IV) antibiotics
                  within 14 days prior to Baseline;

               -  Subject has received vaccination with Bacille Calmette-Guerin (BCG) within 365
                  days prior to Screening or will receive BCG vaccination during study
                  participation including up to 12 months after the last dose of the study drug;

               -  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 3 months after the last dose of study drug.

         13. 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.

         14. Female subject who is pregnant or breast-feeding or considering becoming pregnant
             during the study.

         15. Male subject who is considering fathering a child 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

                  o Subject can be included if WBC count is <2.5 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 creatinine >1.6 mg/dL (>141 µmol/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)

         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.