PSORIASIS
Serum, Cellular, and Imaging Markers of Arthritis in Psoriasis Patients
Psoriatic arthritis (PsA), an inflammatory arthritis associated
with psoriasis, affects approximately 650,000 adults in the
United States and is associated with increased morbidity and
mortality. Joint inflammation and damage arise within the first 2
years of disease in 50% of patients, who manifest bone erosions
and joint space narrowing on plain x-rays.
The events that underlie the conversion from psoriasis to PsA
are not well understood. This conversion occurs 30% of the time
within the first 10 years of psoriasis diagnosis. PsA patients
have about a 50% chance of developing joint damage within the
first 2 years of disease. A biomarker that identifies subclinical
joint inflammation in psoriasis patients would allow for a diagnostic
tool to allow for earlier intervention in psoriasis patients
and provide a better understanding of the underlying molecular
pathogenesis that may lead to development of new therapeutic
targets in PsA.
The advent of tumor necrosis factor antagonists for treatment
of PsA has dramatically improved clinical response and slowed
bone and cartilage degradation. Nevertheless, up to 45% of patients
do not meet primary endpoints in clinical trials, which
underscores the need for new therapeutic options. The researchers’
long-term goals are to: 1) develop arthritis biomarkers in
psoriasis patients that will facilitate early treatment interventions;
and 2) identify new therapeutic targets in PsA through
better understanding the underlying molecular pathogenesis.
A First in Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of an Intravenous Dose of GSK2831781 in Healthy Subjects and Patients With Plaque Psoriasis
This study is a phase I, randomised, double blind (sponsor
unblinded), placebo-controlled, single ascending dose study
GSK2831781 administered by IV. GSK2831781 is a humanized
antibody dependent cell cytotoxicity enhanced monoclonal
afucosylated antibody that is specific to the lymphocyte activation
gene-3 (LAG-3) protein. This is the first administration of
GSK2831781 in humans and will evaluate in 2 parts the safety,
tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity
of single IV doses of GSK2831781 administered to
healthy subjects previously vaccinated with Bacillus Calmette
Guérin (BCG) (Part A, delayed type hypersensitivity [DTH] cohorts)
and patients with plaque psoriasis (Part B).
The inclusion of DTH and psoriasis subjects to explore the
mechanism in biopsies and clinical response endpoints in
these populations, as well as investigate systemic biomarkers,
will provide useful information prior to conducting studies in
other immune-inflammatory diseases, which will involve more
invasive tissue biopsies. Measuring the pharmacology of
GSK2831781 using the depletion of LAG-3 + T-cells in skin biopsies
from tuberculin purified protein derivative skin challenge
and lesional skin biopsies from patients with psoriasis will be
helpful in understanding the dose response relationship, which
will be important for designing future studies in immuno-inflammatory
diseases, including psoriasis. Approximately 63 subjects
will be enrolled to complete dosing and critical assessments. The
subject numbers will be split to approximately 31 healthy subjects
(Part A) and 32 patients with psoriasis (Part B).
ONYCHOMYCOSIS
Study to Evaluate the Efficacy and Safety of P-3058 10% Nail Solution in the Treatment of Toenail Onychomycosis
The purpose of this multicenter, randomized, double-blind,
parallel, vehicle-controlled study is to evaluate the efficacy and
safety of P-3058 10% nail solution as a safe and effective treatment
for onychomycosis. Complete cure of the target great
toenail is defined as negative potassium hydroxide (KOH) microscopy,
negative culture for dermatophytes, and target nail
