Microsoft word - fst100avc005 brazil protocol synopsis

Clinical Trial Protocol: FST100-AVC-005 SYNOPSIS
Protocol Title:
A Proof-of-Concept, Multi-Center, Randomized, Double-Masked Study to Evaluate the Clinical Efficacy and Safety of FST-100 (0.1% Dexamethasone and 0.6% PVP-Iodine ) ophthalmic suspension in the Treatment of Acute Viral Conjunctivitis. Protocol Number:
Study Drug:
1. FST-100 (0.1% dexamethasone and 0.6% PVP-Iodine) ophthalmic suspension (Foresight Biotherapeutics, Inc. New York, NY) Study Phase:
Primary Objective(s):
To evaluate the clinical efficacy and safety of FST-100 in the treatment of acute viral conjunctivitis. Secondary Objective(s):
Overall Study Design:
Structure:
Multi-center, double masked, vehicle-controlled, safety and efficacy study with open label extension. Duration:
Controls:
Dosage/Dose Regimen:
Subjects will be randomized in a 1:1 fashion to one of the following groups: 1. FST-100 (0.1% dexamethasone and 0.6% PVP- Iodine) ophthalmic suspension (Foresight Biotherapeutics, Inc. New York, NY) One to two drops of the study medication will be instilled in the affected eye (s) QID on days 1-5. If signs of acute viral conjunctivitis are still present during Visit 3 exam, subjects will be dispensed open label FST-100 and instructed to dose QID for 5 additional days. Clinical Trial Protocol: FST100-AVC-005 Summary of Visit Schedule:
The study consists of four visits over 12-14 days. Visit 1 will occur on Day 1, Visit 2 will occur on Day 3+1 day window, Visit 3 will occur on Day 6 +1 day window and Visit 4 will occur on Day 12-14 (Visit 3 + 6-7 days). Measures Taken to Reduce
Subjects will be randomly assigned to receive one of the two treatments. The subjects and the study staff will not know which treatment the subjects are assigned to receive. Study Population
Characteristics:
Number of Subjects:
Approximately 132 subjects will be enrolled to complete approximately 120 evaluable subjects (60 per treatment arm).
Condition/Disease:
Inclusion Criteria:
Be at least 18 years of age at Visit 1 (Day 0, Baseline) of either sex or any race. Be willing and able to provide consent, either written or if the subject is not able to read, provide consent as stipulated by local laws and local Ethics Committee guidelines (i.e finger print and witness signature). Be willing and able to follow all instructions and attend all study visits. Be willing to avoid disallowed medications and treatments (see exclusions 10, 11, 12 and 13) for the duration of the study. Be willing to discontinue contact lens wear for the duration of the study. Agree to submit to a pregnancy test at Visit 1 prior to enrollment and at Study Exit, or not be of childbearing potential. Agree to use an acceptable method of contraception for the duration of the study or not be of childbearing potential. Acceptable methods of birth control include: spermicide with barrier, oral, transdermal, injectible, or implantable contraception, IUD, abstinence, and surgical sterilization of partner. Female subjects are not of childbearing potential if they have had a hysterectomy, bilateral oophorectomy, bilateral tubal ligation, or are post-menopausal by at least 12 months. Have a Best Corrected Visual Acuity (BCVA) of 0.60 logMAR or better in each eye as measured using an EDTRS chart. Clinical Trial Protocol: FST100-AVC-005 Report presence of acute viral conjunctivitis less than or equal to five (5) days prior to Visit 1. Have a clinical diagnosis of suspected acute viral conjunctivitis in at least one eye and the presence of the following minimal clinical signs: Conjunctival hyperemia (a minimum grade of ‘1’ on 0-3 scale) Watery conjunctival discharge (a minimum grade of ‘1’ on a 0-3 scale) Note: Selection of study eye will be based on whichever eye has the greater cumulative score for hyperemia and discharge at the baseline visit. Exclusion Criteria:
Have known sensitivity or poor tolerance to corticosteroids, to PVP-Iodine, or to any other component of the study medications. Have a history of ocular surgical intervention within six (6) weeks prior to Visit 1 or during the study. Have presence of any active ocular inflammation (e.g. uveitis or iritis), other than acute viral conjunctivitis. Have clinical signs or presence of an ocular infection other than acute viral conjunctivitis (i.e. bacterial or fungal). Have clinical signs, presence or a history of herpes simplex keratitis. Be a known intraocular pressure steroid responder, have a history of glaucoma or have a known history of intraocular pressure greater than 21 mmHg. Have clinically significant optic nerve defects visible upon non-dilated fundus examination. Have a history of recurrent corneal erosion syndrome, either idiopathic or secondary to previous corneal trauma or dry eye syndrome. Be unable to discontinue contact lens wear for the duration of the study. Have used any topical ocular or systemic anti-virals within 7 days of enrollment. Have used any topical ocular, aerolized/nebulized, or systemic corticosteroid agents within 14 days of enrollment. Stable (greater than 1 month prior to enrollment) use of inhaled (using mouthpiece) and nasal corticosteroids and topical dermal steroids (except around the eyes) are allowed. Dose must Clinical Trial Protocol: FST100-AVC-005 continue unchanged for the duration of the study. Have used any topical ophthalmic solutions, including tear substitutes and diagnostics, within 2 hours of Visit 1 and be unable to discontinue use of all topical ophthalmic solutions (including diagnostics) for the duration of the study. Be currently pregnant, nursing, or planning a pregnancy; or be a woman that has a positive pregnancy test. Have any uncontrolled systemic disease or debilitating disease (e.g., cardiovascular disease, hypertension, diabetes, or cystic fibrosis). Have prior (within 30 days of beginning study treatment) or anticipated concurrent use of an investigational drug or device. Have a condition or a situation which, in the Investigator’s opinion, may put the subject at increased risk, confound study data, or interfere significantly with the subject’s study participation. Study Formulations and
Formulation Numbers:

Evaluation Criteria:
Efficacy Measures:
The primary efficacy variable is clinical resolution of acute viral conjunctivitis in the study eye at Visit 3. Clinical resolution is defined as the absence (score=0) of bulbar conjunctival injection and watery conjunctival discharge. The secondary efficacy variable is decrease in viral load as determined by polymerase chain reaction (PCR) at Visit 3. Safety Measures:
Clinical Trial Protocol: FST100-AVC-005 General Statistical Methods and Types of Analyses
Primary Efficacy Analysis
The primary efficacy variable is clinical resolution of acute viral conjunctivitis in the study eye
at Visit 3.
The primary population for the efficacy analysis will be based on the intent to treat (ITT)
sample, comprising all subjects who entered the study and received at least one dose of the study
medication. Clinical resolution is defined as the absence (score = 0) of the following two clinical
signs: watery conjunctival discharge and bulbar conjunctival injection. A chi-sq or Fisher’s exact
test (in the case of expected counts less than 5) will be used to compare the Drug Product and
vehicle groups with respect to the proportion of subjects with clinical resolution at Visit 3.
Safety
The safety of dexamethasone/PVP-Iodine will be assessed using data listings and statistical
summaries for each treatment group at each time point. Safety will be evaluated by the incidence
of adverse events, changes in visual acuity and the slit lamp biomicroscopy exam. All subjects
enrolled in the study who received at least one dose of the study medication will be evaluated for
safety. All data will be summarized for safety and identified as data from treated or untreated
eyes. Adverse experience data will be listed and summarized by treatment group, body system,
MedDRA® terms, investigator opinion concerning the relationship of the adverse event to the
drug (definitely related, probably, possibly, unlikely or not related) and severity (1=mild,
2=moderate, 3=severe). Visual acuity changes will be listed for each eye, and the number of
subjects with clinically significant (> 0.2 LogMAR) changes in one or both eyes will be
tabulated for each dose group. Biomicroscopy changes will be tabulated by treatment group, eye
(treated and untreated) and visit. Data from subjects with slit lamp findings at baseline as well as
those with treatment emergent findings (findings that were not present prior to treatment or a
worsening relative to the pretreatment baseline) will be listed. Summary statistics for continuous
data will include computations of the mean, standard deviation, minimum and maximum.
Frequency distributions will be provided for discrete variables.
The demographic characteristics (i.e. age, sex, and race and iris color), medical history, and
ocular history data will be summarized by treatment group for the total study sample. These data
will be listed by treatment group for the completed, terminated, and discontinued subjects.
Summary of Known and Potential Risks and Benefits to Human Subjects
Dexamethasone is available in 0.1% concentrations for over four decades in the commercial
ophthalmic products like Maxitrol (dexamethasone 0.1%; neomycin sulfate (EQ 3.5mg base/mL;
polymyxin B sulfate 10,000 units/mL), Maxidex (0.1% dexamethasone ophthalmic suspension;
Alcon Laboratories, Inc) and TobraDex (tobramycin 0.3%/dexamethasone 0.1%). Given this
long history, there is extensive safety data available for ophthalmic applications of
dexamethasone.
Risks involved with the use of 0.1% dexamethasone include glaucoma with optic nerve damage,
visual acuity and field defects; cataract formation; secondary ocular infection following
suppression of host response; and perforation of the globe.
Clinical Trial Protocol: FST100-AVC-005 PVP-Iodine is a broad spectrum antiseptic with no known microbial resistance. It kills infectious organisms by iodination of lipids, oxidation of cytoplasmic and membrane compounds and provides significant antimicrobial activity. Based upon its mechanism of action, the antiviral activity of PVP-Iodine should be retained regardless of viral serotype. Iodine and iodine derivatives have a history of being used to treat ophthalmic, otic, oral, dermal, and other infections. They possess potent broad-spectrum antimicrobial activity and the local delivery of these agents to the site of infection is known to effectively treat, eliminate, and/or prevent the growth of microorganisms. An ophthalmic preparation of 5% PVP-Iodine (Betadine®) is available for preparation of the periocular region and irrigation of the ocular surface. Approximately 25 years of safety data is available for ophthalmic applications of PVP-Iodine. However, local sensitivity has been exhibited by some individuals to 5% povidone-iodine ophthalmic solution. The study drug, FST-100 for the ophthalmic indication, acute viral conjunctivitis has a concentration of PVP-Iodine of 0.6%, which is significantly lower than that found in the commercial preparation.

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