A Prospective, Multi-Center, Randomized, Double-Masked, Positive-Controlled Phase 3 Clinical Trial Designed to Evaluate the Safety and Efficacy of Iontophoretic Dexamethasone Phosphate Ophthalmic Solution Compared to Prednisolone Acetate Ophthalmic Suspension (1%) in Patients With Non-Infectious Anterior Segment Uveitis
Anterior uveitis is a disorder of the eye associated with intraocular inflammation of the
anterior portion of the uvea, particularly the iris and/or ciliary body. It is distinct from
other iterations of uveitis such as posterior, diffuse and intermediate uveitis although it
is the most common form of uveitis and accounts for approximately 75% of cases.
In a Phase 1/2 study (EGP-437-001), the delivery of EGP-437 (40 mg/mL dexamethasone
phosphate solution) at four different iontophoresis dose levels was studied in 40 subjects
with non-infectious anterior segment uveitis. The study demonstrated that a single EGP-437
treatment: lowered anterior chamber cell (ACC) scores in the majority of patients without
requiring additional treatment; produced low short-term systemic exposure to dexamethasone
and dexamethasone phosphate; and produced the most beneficial effects in the 1.6 and 4.8
mA-min dose groups; and caused mainly minor AEs and no non-ocular systemic corticosteroid
mediated effects were observed.
The Phase 3 study is intended to confirm and extend the results from the Phase 2 study. The
study is designed to assess the safety and efficacy Ocular Iontophoresis with EGP-437 4.0
mA-min at 1.5 mA and accompanying placebo eyedrops in comparison to Ocular Iontophoresis
with sodium citrate buffer solution 4.0 mA-min at 1.5 mA and accompanying prednisolone
acetate (1%) eyedrops for the treatment of non-infectious anterior segment uveitis.
CardioMEMSTM HF System Post Approval Study
RATIONALE: Heart failure is a major cause of morbidity and mortality. CardioMEMS HF System is an FDA approved implantable device that wirelessly measures and monitors pulmonary arterial pressure and heart rate. The CHAMPION trial demonstrated that management of heart failure using pulmonary artery pressure information obtained with the CardioMEMS HF System, in addition to traditional signs and symptoms, reduced HF hospitalizations.
INTERVENTION: Patients will be scheduled for follow-up visits at 1 month and every 6 months for 2 years. Following sensor implant and hospital discharge, subjects will take PA pressure measurements on a daily basis, or as directed by the investigator. These measurements will be automatically transmitted to the secure Patient database (CardioMEMS HF website).
OBJECTIVES: The objective of this study is to confirm the post-market safety and effectiveness of the CardioMEMS HF System to premarket.
STUDY POPULATION: Twelve hundred subjects will be enrolled with at least 35% of the enrolled patients being women (420 women out of 1200). Enrollment will be limited to 15% of the total study population at any one site.
STUDY METHODOLOGY: This is a prospective, multi-center, open-label trial conducted in the United States (US). All subjects who sign the informed consent form and satisfy the inclusion/exclusion criteria will be enrolled into the CardioMEMS HF System PAS and will be scheduled for follow-up visits at 1 month and every 6 months for 2 years. Following sensor implant and hospital discharge, subjects will take PA pressure measurements on a daily basis, or as directed by the investigator. These measurements will be automatically transmitted to the secure Patient database (CardioMEMS HF website).
STUDY ENDPOINTS:Primary safety endpoints will be evaluated at 2 years: 1) freedom from device/system related complications and 2) freedom from pressure sensor failure.
STATISTICS: The primary safety hypotheses are that the device / system-related complication-free proportion of subjects will be at least 80% at 24 months (OPC used in the CHAMPION trial) and that the pressure sensor failure-free proportion of subjects will be at least 90% at 24 months (OPC used in the CHAMPION trial). Plotting and analysis of safety endpoints will also be displayed using Kaplan-Meier methods. All safety analyses will be performed on the safety population.
Pilot Study for Evaluation of Glatiramer Acetate in RRMS Patients With Comorbid Autoimmune Conditions
Multiple Sclerosis (MS) is an auto-immune neurodegenerative disease that affects more than
400,000 individuals in the United States, and 2.5 million worldwide
(www.nationalmssociety.org). The main pathogenic mechanism in MS involves an inflammatory
condition that damages the myelin of the central nervous system (CNS), resulting in axonal
damage and neurological impairment, often leading to severe disability. MS is one of the
most common causes of neurological disability in young and middle-aged adult individuals,
and as such has a tremendous physical, psychological and social impact on patients' lives.
MS is a complex disease diagnosed by McDonald criteria with different clinical and
pathological phenotypes. Several forms of MS have been described: Relapsing-Remitting
(RRMS), Secondary-Progressive MS (SPMS), Progressive-Relapsing MS (PRMS), and
Primary-Progressive MS (PPMS).
Glatiramer Acetate (GA) and Beta-Interferons (β-IFNs) are well established first-line
immunomodulating treatment options for relapsing remitting multiple sclerosis (RRMS) with
excellent safety profiles. The mechanisms of action of GA and IFNs are different. It is well
known that in general Disease-Modifying Treatments (DMTs) reduce relapse rate in more than
half of the multiple sclerosis (MS) patients who receive DMT, while having little if any
effect on the rest. It has been speculated that the response to beta-interferons or GA may
have genetic basis. As Axtell RC et al. indicated the experimental autoimmune
encephalomyeilits (EAE) in mouse caused by TH1 cells generally respond well to
interferon-beta, while EAE caused by TH17 cells get worse with interferon-beta.
Autoimmune disease is an extreme situation where the autoimmune response overshoots and goes
out of control. The other extreme is a degenerative disorder, where the autoimmune response
is not strong enough for effective protection, and degeneration therefore continues. GA
being an immunomodulator may provide both properly regulated immune suppression (in the case
of autoimmune disease) and properly regulated immune activation (in the case of the
neurodegenerative disease).
Autoimmune conditions cluster in families with high risk for multiple sclerosis than in
general population which suggests that the disease might arise on a background of a
generalized susceptibility to autoimmunity. Occurrence of psoriasis, autoimmune thyroiditis,
vasculitis, rheumatoid arthritis, scleroderma, lupus are seen more commonly in MS patients.
Many of these patients initially get started on beta-IFNs, and usually do not do well on
them. According to Investigator's and the USC MS Comprehensive Care Center experience,
autoimmune co-morbidity associated with MS can serve as a biological marker predicting good
response to GA and unfavorable response to the IFNs.
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