Study of the Clinical Activity, Safety, and Tolerability of SRT2104 in Subjects With Moderate to Severe Plaque-Type Psoriasis
Condition: Psoriasis
MeSH terms: Psoriasis
Intervention: Placebo; SRT2104
Intervention description: For the placebo product, the SRT2104 drug substance will be replaced by microcrystalline cellulose (Avicel® PH 105) to match the SRT2104 investigational product.; SRT2104 drug substance is a new chemical entity which is supplied as a fine, yellowish/amber powder. The SRT2104 investigational product is prepared by packing 250 mg of micronized SRT2104 powder with no additional additives into a size 00 opaque, hard gelatin capsule, packaged in dosing bottles containing a single daily dose.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      This double-blind, placebo-controlled study will be conducted at 5 study centers in the
      United States. Approximately 30 subjects with moderate to severe plaque-type psoriasis will
      take part. The study will consist of a screening period of up to 21 days, a 12-week treatment
      period with 7 on-treatment clinic visits (approximately one every 2 weeks) and a post-dosing
      follow-up clinic visit approximately 30 days after the last dose of study drug is taken.

      Subjects will be randomized to receive either 250mg, 500mg or 1000mg of study drug or
      placebo. Study drug will be taken by mouth on a full stomach, every day for 84 days.

      Vital signs, clinical laboratory results (hematology, chemistry, and urinalysis), ECGs and
      physical examinations will be assessed at periodic intervals from Day 1 through Day 84.

      A skin biopsy will be taken at the beginning and the end of the dosing period to evaluate any
      effects of the study drug on psoriasis. Investigators will perform other psoriasis
      evaluations (including the Psoriasis Area and Severity Index [PASI] and the Physician's
      Global Assessment [PGA] at 5 different times throughout the study to quantify the effects of
      SRT2104 on psoriasis activity.

      Subjects will complete questionnaires throughout the study, to document their sense of
      well-being and mood at 4 different times during the study.

      Five blood samples will be obtained at different timepoints during the study, to measure the
      amount of SRT2104 in the body.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Able and willing to provide written informed consent to participate in the study

          -  Be male or female aged 18 to 80 years (inclusive)

          -  Have a diagnosis of clinically confirmed, stable (without recent documented flare
             within 30 days prior to the Screening Visit), plaque-type psoriasis for at least 6
             months involving ≥10% of body surface area

          -  Have a baseline PASI of ≥10

          -  Be a candidate for systemic psoriasis therapy, in the opinion of the investigator

          -  If a female subject of child-bearing potential, be willing to use reliable
             contraception for the duration of the study, through the 30 day safety follow up
             telephone call

          -  Be willing and able to comply with the protocol for the duration of the study

        Exclusion Criteria:

          -  Has received systemic non-biologic psoriasis therapy or PUVA phototherapy within 4
             weeks prior to the Screening Visit, or had topical psoriasis treatment or UVB
             phototherapy within 2 weeks prior to the Screening Visit

          -  Has received previous treatment with biologic agents within 5 drug half-lives (or
             within 3 months if half-life is unknown) prior to the first dose of SRT2104

          -  Has received a live vaccination within 4 weeks prior to the Screening Visit or intends
             to have a live vaccination during the course of the study

          -  Use of any other non-psoriatic prescription drug therapy, with the exception of any
             prescription medication administered at a stable dose for at least 6 weeks prior to
             the Screening Visit; however, the administration of proton pump inhibitors during the
             study dosing period is prohibited

          -  Use of any dietary or herbal supplements, with the exception of those administered at
             a stable dose for at least 6 weeks prior to the Screening Visit

          -  Has received any investigational drug or experimental procedure within 30 days prior
             to the first dose of SRT2104

          -  Has an active infection (e.g., sepsis, pneumonia, abscess, etc.) or be at high risk of
             developing an infection, in the opinion of the investigator, prior to the first dose
             of SRT2104

          -  Has a history of a positive tuberculosis test or a positive tuberculosis test at the
             Screening Visit that cannot be attributed to a prior BCG inoculation

          -  Has a positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody
             result within 3 months of the Screening Visit

          -  Has a positive test for HIV antibody

          -  Has an abnormal chest x-ray at the Screening Visit which, in the opinion of the
             investigator, would preclude entry into the trial

          -  Has a 12-lead electrocardiogram (ECG) with changes considered to be clinically
             significant on medical review including prolonged QTc intervals as defined below:

          -  QTcB ≥450 msec (based on single or average QTc value of triplicate ECGs obtained over
             a brief period)

          -  QTcB ≥480 msec in subjects with Bundle Branch Block

          -  Has renal or liver impairment, defined as:

          -  Serum creatinine level of ≥ 1.4 mg/dL for females and ≥ 1.5 mg/dL for males

          -  AST and ALT ≥ 2xULN or

          -  Alkaline phosphatase and bilirubin > 1.5xULN (an isolated bilirubin >1.5xULN is
             acceptable if bilirubin is fractionated and direct bilirubin is <35%)

          -  Has active neoplastic disease or history of neoplastic disease within 5 years of study
             entry (except for basal or squamous cell carcinoma of the skin, or carcinoma in situ
             which have been definitively treated with standard of care approaches)

          -  Is pregnant or breast-feeding. Confirmation that a female subject is not pregnant must
             be established by negative pregnancy tests at Screening and Day 1

          -  Has a significant history of alcoholism or drug/chemical abuse, or consumes more than
             3 standard units/day of alcohol. A standard unit of alcohol is defined as 250 mL of
             beer, 25 mL of spirit, or 125 mL of wine

          -  History of sensitivity to any of the study medications, or components thereof, or a
             history of drug or other allergy that, in the opinion of the investigator or medical
             monitor, contraindicates their participation

          -  Has an acute or chronic illness which, in the opinion of the investigator, could pose
             a threat or harm to the subject