Randomized Placebo-controlled Study of ISA247 in Plaque Psoriasis
Condition: Psoriasis
MeSH terms: Psoriasis
Intervention: voclosporin; Placebo
Intervention description: voclosporin 0.2, 0.3, or 0.4 mg/kg po BID; Placebo
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 451.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Randomized Controlled Trials; Immunosuppression; Adult; Chronic Disease; Dermatologic Agents; Female; Humans; Male; Middle Aged; Severity of Illness Index; Treatment Outcome; Quality of Life; Double-Blind Method

Summary:

      The purpose of this study is to determine which dose of voclosporin is effective in the
      treatment of plaque psoriasis compared to placebo.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Plaque psoriasis ≥ 6 months prior to screening.

          -  Diagnosis of stable, plaque psoriasis; i.e. psoriasis must not be spontaneously
             improving or worsening in the 4 weeks prior to the screening visit.

          -  Plaque psoriasis involving ≥10% of the body surface area (BSA) at screening and prior
             to randomization at the day 0 visit.

          -  PASI score ≥10 at screening and prior to randomization at the day 0 visit.

          -  Not pregnant or nursing or planning to become pregnant during the course of the study.

          -  Sexually active women of childbearing potential or less than 1 year post-menopausal
             and sexually active men who are not surgically sterile must use a reliable form of
             birth control during study treatment and for at least 3 months after the last dose of
             study drug. Surgically sterile females are not considered to be of childbearing
             potential. Reliable forms of birth control include oral or depot contraceptives, and
             double-barrier methods.

          -  Written informed consent prior to washout and screening procedures.

          -  Able to keep study appointments and cooperate with all study requirements, in the
             opinion of the investigator.

        Exclusion Criteria:

          -  Has generalized erythrodermic, guttate, or pustular psoriasis.

          -  Have other dermatoses that would interfere with the evaluation of psoriasis, at the
             discretion of the investigator.

          -  A current malignancy or history of malignancy within 5 years or a history of lymphoma
             at any time. Subjects can be enrolled with a history of squamous or basal cell
             carcinoma that has been surgically excised or removed with curettage and
             electrodesiccation.

          -  Has current, uncontrolled bacterial, viral, or fungal infections that require
             intravenous antibiotics or antifungals or had had such infections within 60 days prior
             to screening.

          -  A history of streptococcal infection that required oral antibiotics within 30 days
             prior to screening.

          -  A known history of tuberculosis.

          -  Serologic evidence or known latent human immunodeficiency virus (HIV), hepatitis B
             (HBV) or hepatitis C (HCV) virus.

          -  Uncontrolled hypertension as defined by systolic blood pressure ≥150 mm Hg or
             diastolic blood pressure ≥ 90 mm Hg.

          -  MDRD GFR ≤ 60 ml/min.

          -  Variation between the screening and Visit 1 GFR ≥30%.

          -  Alanine transaminase, aspartate transaminase, or gamma-glutamyl transferase ≥ 3x upper
             limit of normal (ULN).

          -  White blood cell count ≤ 2.8 x 109/L.

          -  Triglycerides ≥ 3x ULN.

          -  Requires the following prohibited medications or treatments during the washout or
             treatment period: drugs potentiating the nephrotoxicity of voclosporin such as NSAID's
             or ACE inhibitors, drugs interfering with its pharmacokinetics; drugs considered to
             contribute to psoriasis flare; or, systemic and topical psoriasis medication
             (including psoralen/ultraviolet A light treatment) that may interfere with assessment
             of study drug efficacy.

          -  Has used any investigational drug or device within 28 days or 5 half lives (whichever
             is longer) prior to the screening visit.

          -  Has taken biological agent(s), except flu shots, tetanus shots, or boosters, within 3
             months of the start of treatment. Biological agents include any virus, therapeutic
             serum, toxin, antitoxin, or analogous product applicable to the prevention, treatment,
             or cure of diseases or injuries of man.

          -  Previous exposure to voclosporin.

          -  A history of clinically defined allergy to cyclosporine or any of the constituents of
             the voclosporin formulation (vitamin E, medium chain triglyceride oil, Tween 40,
             ethanol).

          -  A history of alcoholism or drug addiction within 1 year prior to study entry.

          -  Weighs <45 kg (99 lbs) or > 140 kg (308 lbs).

          -  A history of disease, including mental/emotional disorder that would interfere with
             the subject's participation in the study, or that might cause the administration of
             ISA247 to pose a significant risk to the subject, in the opinion of the investigator.