Phase 2 Completed N=40 Randomized Double-blind Treatment

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

Source: ClinicalTrials.gov NCT01154101 ↗

Enrolled (actual)

Serious AEs

7.7%

Results posted

Oct 2017

Primary outcomePrimary: 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 — 1; 3; 4; 2 Participants

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.

Outcome Measures

Outcome	Result	p-value
PRIMARY 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	1; 3; 4; 2	—
PRIMARY Number of Participants With Any Adverse Events (AE) and Serious Adverse Events (SAE)	3; 4; 9; 11; 0; 2	—
PRIMARY Number of Participants With Hematology and Coagulation Abnormalities of Potential Clinical Concern	0; 0; 1; 2	—
PRIMARY Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance	4; 3; 5; 5	—
PRIMARY Number of Participants With Abnormal Electrocardiogram (ECG) Values	3; 1; 4; 6	—
PRIMARY Number of Participants With Vital Signs of Potential Clinical Importance	0; 0; 0; 2	—
SECONDARY Number of Participants With Clinical Activity in Psoriasis Area and Severity Index (PASI) Score After 4, 8, and 12 Weeks of Exposure	2; 1; 3; 7; 0; 0	—
SECONDARY Summary of Physician's Global Assessment (PGA) Score After 4, 8 and 12 Weeks of Exposure	1; 0; 0; 1; 2; 1	—
SECONDARY 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	2148.08; 4189.46; 8358.45	—
SECONDARY 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	261.64; 406.67; 1005.89	—
SECONDARY Change From Baseline in Fibroblast Growth Factor 21 (FGF21) as an Indicator of the Pharmacodynamic Effects of SRT2104	-61.67; -94.53; 56.93; 329.82; -67.04; -72.72	—
SECONDARY Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) as an Indicator of the Pharmacodynamic Effects of SRT2104	0.11; -0.14; 1.18; -0.96; 0.59; -0.18	—

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 i

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Data sourced from ClinicalTrials.gov (NCT01154101). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.