Clinical trial NCT01154101: Study of the Clinical Activity, Safety, and Tolerability of SRT2104 in Subjects With Moderate to Severe Plaque-Type Psoriasis
Official title: A Randomized, Double-Blind, Placebo-Controlled, Phase IIa Study of the Clinical Activity, Safety, and Tolerability of SRT2104 in Subjects With Moderate to Severe Plaque-Type Psoriasis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Psoriasis
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
Collaborators: name: GlaxoSmithKline
First posted: 2010-06-30
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: Assessment of Clinical Activity by Improvement Score (Using Krueger Criteria): Number of Participants With Good or Excellent Improvement Score Based on Histological Assessments of Skin Biopsies After 12 Weeks of Exposure
timeFrame: 12 weeks
measure: Number of Participants With Any Adverse Events (AE) and Serious Adverse Events (SAE)
timeFrame: Up to Follow-up (Day 114)
measure: Number of Participants With Hematology and Coagulation Abnormalities of Potential Clinical Concern
timeFrame: Up to Follow-up (Day 114)
measure: Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance
timeFrame: Up to Follow-up (Day 114)
measure: Number of Participants With Abnormal Electrocardiogram (ECG) Values
timeFrame: Up to Follow-up (Day 114)
measure: Number of Participants With Vital Signs of Potential Clinical Importance
timeFrame: Up to Follow-up (Day 114)
Secondary outcomes:
measure: Number of Participants With Clinical Activity in Psoriasis Area and Severity Index (PASI) Score After 4, 8, and 12 Weeks of Exposure
timeFrame: Weeks 4, 8 and 12
measure: Summary of Physician's Global Assessment (PGA) Score After 4, 8 and 12 Weeks of Exposure
timeFrame: Weeks 4, 8 and 12
measure: Area Under Curve (AUC) of 12 Weeks of Dosing With 0.25 g, 0.5 g and 1.0 g SRT2104 in the Fed State in Participants
timeFrame: Pre-dose (30 minutes or less before dosing: 1 sample), 0.5 to 2 hours and 3 to 6 hours post-dose (1 sample), 6 to 22 hours post-dose (2 samples) up to Week 12
measure: Maximum Plasma Concentration (Cmax) of 12 Weeks of Dosing With 250 Milligrams (mg), 500 mg and 1000 mg SRT2104 in the Fed State in Participants
timeFrame: One sample: Pre-dose (30 minutes or less before dosing), One sample: 0.5 to 2 hours post-dose and 3 to 6 hours post-dose and 2 samples 6 to 22 hours post dose, at any Visit 4 (Day 28 or Week 4), Visit 6 (Day 56 or Week 8) or Visit 8 (Day 84 or Week 12)
measure: Change From Baseline in Fibroblast Growth Factor 21 (FGF21) as an Indicator of the Pharmacodynamic Effects of SRT2104
timeFrame: Baseline (Day 1) and Days 28, 56 and 84
measure: Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) as an Indicator of the Pharmacodynamic Effects of SRT2104
timeFrame: Baseline (Day 1) and Days 28, 56 and 84
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: GSK Investigational Site
state: Missouri
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Portland
country: United States
facility: GSK Investigational Site
state: Oregon
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Johnston
country: United States
facility: GSK Investigational Site
state: Rhode Island
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: Seattle
country: United States
facility: GSK Investigational Site
state: Washington
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Krueger JG, Suarez-Farinas M, Cueto I, Khacherian A, Matheson R, Parish LC, Leonardi C, Shortino D, Gupta A, Haddad J, Vlasuk GP, Jacobson EW. A Randomized, Placebo-Controlled Study of SRT2104, a SIRT1 Activator, in Patients with Moderate to Severe Psoriasis. PLoS One. 2015 Nov 10;10(11):e0142081. doi: 10.1371/journal.pone.0142081. eCollection 2015.