Study of the Clinical Activity, Safety, and Tolerability of SRT2104 in Subjects With Moderate to Severe Plaque-Type Psoriasis

This study has been completed.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
GlaxoSmithKline ( Sirtris, a GSK Company )
ClinicalTrials.gov Identifier:
NCT01154101
First received: April 22, 2010
Last updated: November 15, 2012
Last verified: February 2012
  Purpose

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.


Condition Intervention Phase
Psoriasis
Drug: Placebo
Drug: SRT2104
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Histological assessment of skin biopsies after 12 weeks of dosing with SRT2104 will be used as a measure of clinical activity in subjects with moderate to severe plaque type psoriasis [ Time Frame: 84 days ]
  • Number of participants with adverse events and incidence of adverse events will be used as a measure of safety and tolerability of multiple doses of SRT2104 in subjects with moderate to severe plaque-type psoriasis [ Time Frame: 114 days ]

Secondary Outcome Measures:
  • Psoriasis Area and Severity Index (PASI) is an established psoriasis severity assessment tool that will be used as a measure of the effects of SRT2104 in subjects with moderate to severe plaque-type psoriasis after 4, 8, and 12 weeks of exposure [ Time Frame: 114 days ]
  • Physician's Global Assessment (PGA) score will be used as a measure of the effects of SRT2104 in subjects with moderate to severe plaque-type psoriasis after 4, 8, and 12 weeks of exposure [ Time Frame: 114 days ]
  • Plasma levels of SRT2104 will be measured in all subjects on 5 occasions to assess the pharmacokinetics of SRT2104 [ Time Frame: 84 days ]
  • High sensitivity C-reactive protein and FGF-21 levels will be measured as an indicator of the pharmacodynamic effects of SRT2104 [ Time Frame: 84 days ]

Enrollment: 40
Study Start Date: June 2010
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Cohort 2 - 500mg SRT2104/placebo dose group

10 subjects will be randomized 4:1 (SRT2104: placebo) in each of 3 treatment arms (250mg, 500mg, or 1000mg).

Cohort 2 will commence after Cohort 1 has completed 28 consecutive days of dosing, followed by the completion of a safety review by an Independent Safety Review Committee.

Cohort 2 will be administered at approximately the same time every day, approximately 15 minutes following the consumption of food. Subjects must wait at least 1 hour after dosing before consuming additional calories. Dietary recommendations for the meal that precedes dosing will be provided to the study subjects by the clinical site staff.

Drug: Placebo
For the placebo product, the SRT2104 drug substance will be replaced by microcrystalline cellulose (Avicel® PH 105) to match the SRT2104 investigational product.
Drug: SRT2104
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.
Active Comparator: Cohort 3 - 1000mg SRT2104/placebo dose group

10 subjects will be randomized 4:1 (SRT2104: placebo) in each of 3 treatment arms (250mg, 500mg, or 1000mg).

Cohort 3 will commence after Cohort 2 has completed 28 consecutive days of dosing, followed by the completion of a safety review by an Independent Safety Review Committee.

Cohort 3 will be administered four SRT2104 capsules at approximately the same time every day, approximately 15 minutes following the consumption of food. Subjects must wait at least 1 hour after dosing before consuming additional calories. Dietary recommendations for the meal that precedes dosing will be provided to the study subjects by the clinical site staff.

Drug: Placebo
For the placebo product, the SRT2104 drug substance will be replaced by microcrystalline cellulose (Avicel® PH 105) to match the SRT2104 investigational product.
Drug: SRT2104
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.
Active Comparator: Cohort 1 - 250mg SRT2104/placebo dose group

10 subjects will be randomized 4:1 (SRT2104: placebo) in each of 3 treatment arms (250mg, 500mg, or 1000mg).

Cohort 1 will be administered at approximately the same time every day, approximately 15 minutes following the consumption of food. Subjects must wait at least 1 hour after dosing before consuming additional calories. Dietary recommendations for the meal that precedes dosing will be provided to the study subjects by the clinical site staff.

Dosing for Cohort 2 will not commence until Cohort 1 has completed 28 consecutive days of dosing, followed by the completion of a safety review by an Independent Safety Review Committee.

Drug: Placebo
For the placebo product, the SRT2104 drug substance will be replaced by microcrystalline cellulose (Avicel® PH 105) to match the SRT2104 investigational product.
Drug: SRT2104
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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01154101

Locations
United States, Missouri
GSK Investigational Site
St. Louis, Missouri, United States, 63117
United States, New York
GSK Investigational Site
New York, New York, United States, 10065
GSK Investigational Site
New York, New York, United States, 10016
United States, Oregon
GSK Investigational Site
Portland, Oregon, United States, 97223
United States, Pennsylvania
GSK Investigational Site
Philadelphia, Pennsylvania, United States, 19103
United States, Rhode Island
GSK Investigational Site
Johnston, Rhode Island, United States, 02919
United States, Texas
GSK Investigational Site
Dallas, Texas, United States, 75246
United States, Washington
GSK Investigational Site
Seattle, Washington, United States, 98101
Sponsors and Collaborators
Sirtris, a GSK Company
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline ( Sirtris, a GSK Company )
ClinicalTrials.gov Identifier: NCT01154101     History of Changes
Other Study ID Numbers: 114296
Study First Received: April 22, 2010
Last Updated: November 15, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases

ClinicalTrials.gov processed this record on April 22, 2014