Treatment of Bacterial Conjunctivitis With SHP640 Compared to PVP-Iodine and Placebo

Study Overview
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Brief Summary
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The purpose of this study is to determine if an investigational treatment is effective compared with placebo and PVP-Iodine in the treatment of adults and children with bacterial conjunctivitis.

Official Title
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A Phase 3, Multi-center, Randomized, Double-Masked Study to Evaluate the Clinical Efficacy and Safety of SHP640 (PVP-Iodine 0.6% and Dexamethasone 0.1%) Ophthalmic Suspension Compared to Placebo in the Treatment of Bacterial Conjunctivitis

Conditions
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Bacterial Conjunctivitis

Intervention / Treatment
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* Drug: SHP640
* Drug: PVP-I 0.6%
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: An understanding, ability, and willingness to fully comply with study procedures and restrictions (by the parent(s), guardian, or legally authorized representative, if applicable). Ability to voluntarily provide written, signed, and dated (personally or via a parent(s), guardian, or legally authorized representative(s) informed consent (and assent, if applicable) to participate in the study. Participants of any age at Visit 1 (Note: participants less than (<) 3 months of age at Visit 1 must have been full-term, that is (ie,) greater than or equal to (>=) 37 weeks gestational age at birth). Have a negative AdenoPlus® test in both eyes within 24 hours of Visit 1 or at Visit 1. Have a clinical diagnosis of suspected bacterial conjunctivitis in at least 1 eye confirmed by the presence of the following minimal clinical signs and symptoms in that same eye: Report presence of signs and/or symptoms of bacterial conjunctivitis for less than or equal to (<=) 4 days prior to Visit 1 Bulbar conjunctival injection: a grade of >= 1 on 0-4 scale of Bulbar Conjunctival Injection Scale Ocular conjunctival discharge: a grade of >= 1 (mild) on a 0-3 scale of Ocular Conjunctival Discharge Scale Be willing to discontinue contact lens wear for the duration of the study. Have a Best Corrected Visual Acuity (BCVA) of 0.60 logMAR or better in each eye as measured using an Early Treatment Diabetic Retinopathy Study (ETDRS) chart. BCVA will be assessed by an age appropriate method in accordance with the AAP Policy Statement for Visual System Assessment in Infants, Children, and Young Adults by Pediatricians (Donahue and Baker, 2016; American Academy of Pediatrics, 2016). The policy statement recommends formal vision screening can begin at 3 years of age. VA measurements for children under the age of 3 will be done at the discretion of the investigator. If not done, child should be able to fixate on and follow a moving object, except participants < 2 months of age who have not yet developed this ability. Participants < 2 months will be enrolled at the discretion of investigator. Male, or non-pregnant, non-lactating female who agrees to comply with any applicable contraceptive requirements of the protocol or females of non-childbearing potential. Exclusion Criteria: Current or recurrent disease that could affect the action, absorption, or disposition of the investigational product, or clinical or laboratory assessments, per investigator's discretion. Current or relevant history of physical or psychiatric illness, any medical disorder that may make the participant unlikely to fully complete the study, or any condition that presents undue risk from the investigational product or procedures. Have known or suspected intolerance or hypersensitivity to the investigational product, closely related compounds, or any of the stated ingredients. Prior enrollment in a FST-100 or SHP640 clinical study. Participants who are employees, or immediate family members of employees (who are directly related to study conduct), at the investigational site. Have a history of ocular surgical intervention within <= 6 months prior to Visit 1 or planned for the period of the study. Have a preplanned overnight hospitalization during the period of the study. Have presence of any intraocular, corneal, or conjunctival ocular inflammation (example [eg,] uveitis, iritis, ulcerative keratitis, chronic blepharoconjunctivitis), other than bacterial conjunctivitis. Have active or a history of ocular herpes. Have at enrollment or within <= 30 days of Visit 1, a clinical presentation more consistent with the diagnosis of non-infectious conjunctivitis (except presumed seasonal/perennial allergic conjunctivitis) or non-bacterial ocular infection (eg, viral, fungal, acanthamoebal, or other parasitic). Note: history or concomitant presence of presumed seasonal or perennial allergic conjunctivitis signs/symptoms is not exclusionary. Neonates or infants (ie, participants less than 12 months of age) who have suspected or confirmed (based on the result of any test conducted prior to screening) conjunctivitis of gonococcal, chlamydial, herpetic or chemical origin. Neonates or infants (ie, participants less than 12 months of age) whose birth mothers had any sexually transmitted disease within 1 month of delivery or any history of genital herpes. Presence of nasolacrimal duct obstruction at Visit 1 (Day 1). Presence of any significant ophthalmic condition (eg, Retinopathy of Prematurity, congenital cataract, congenital glaucoma) or other congenital disorder with ophthalmic involvement that could affect study variables. Be a known intraocular pressure (IOP) steroid responder, have a known history or current diagnosis of glaucoma or be a glaucoma suspect. Have any known clinically significant optic nerve defects. Have a history of recurrent corneal erosion syndrome, either idiopathic or secondary to previous corneal trauma or dry eye syndrome; presence of corneal epithelial defect or any significant corneal opacity at Visit 1. Presence of significant, active condition in the posterior segment that requires invasive treatment (eg, intravitreal treatment with vascular endothelial growth factor inhibitors or corticosteroids) and may progress during the study participation period. Have used any topical ocular or systemic antibiotics within <= 7 days of enrollment. Have used any topical ocular non-steroidal anti-inflammatory drugs within <= 1 day of enrollment. Have used any topical ophthalmic steroids in the last <= 14 days. Have used any systemic corticosteroid agents within <= 14 days of Day 1. Stable (initiated >= 30 days prior to enrollment) use of inhaled and nasal corticosteroids is allowed, given no anticipated change in dose for the duration of the study. Topical dermal steroids are allowed except in the periocular area. Have used non-corticosteroid immunosuppressive agents within <= 14 days of Day 1. Have used any topical ophthalmic products, including tear substitutes, and over-the-counter preparations such as lid scrubs, within 2 hours of Visit 1 and be unable to discontinue all topical ophthalmic products for the duration of the study. Use of hot or cold compresses is also not permitted during the study. Have any significant ocular disease (eg, Sjogren's syndrome) or any uncontrolled systemic disease or debilitating disease (eg, cardiovascular disease, hypertension, sexually transmitted diseases/infections, diabetes, or cystic fibrosis) that may affect the study parameters, per investigator's discretion. Any known history of immunodeficiency disorder or known active conditions predisposing to immunodeficiency, such as human immunodeficiency virus, hepatitis B or C, evidence of active hepatitis A (anti-hepatitis A virus immunoglobulin M), or organ or bone marrow transplantation. Within 30 days prior to the first dose of investigational product: Have used an investigational product or device, or Have been enrolled in a clinical study (including vaccine studies) that, in the investigator's opinion, may impact this Shire-sponsored study.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SHP640<br>Participants will instill 1 drop of SHP640 (povidone-iodine [PVP-I] 0.6 percent [%] and Dexamethasone 0.1%) ophthalmic suspension in each eye 4 times daily (QID) for 7 days. | Drug: SHP640<br>* Instill 1 drop of SHP640 (povidone-iodine [PVPI] 0.6% and Dexamethasone 0.1%) ophthalmic suspension in each eye QID (with a minimum of 2 hours between doses) for 7 days.<br>|
| Active Comparator: PVP-I 0.6%<br>Participants will instill 1 drop of PVP-I 0.6% ophthalmic solution in each eye 4 times QID for 7 days | Drug: PVP-I 0.6%<br>* Instill 1 drop of PVP-I 0.6% ophthalmic solution in each eye 4 times QID (with a minimum of 2 hours between doses) for 7 days.<br>|
| Placebo Comparator: Placebo<br>Participants will instill 1 drop of placebo ophthalmic solution in each eye 4 times QID for 7 days. | Drug: Placebo<br>* Instill 1 drop of placebo ophthalmic solution in each eye 4 times QID (with a minimum of 2 hours between doses) for 7 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Clinical Resolution Among Who Received SHP640 or Placebo on Day 5 | Clinical resolution was defined as absence (score=0) of bulbar conjunctival injection and ocular conjunctival discharge in the study eye. Bulbar conjunctival injection was assessed based on 0 (Normal conjunctival vascular pattern) - 4 (Markedly prominent, intense diffuse hyperemia) scale which used pictures from validated bulbar redness (VBR) scale. Ocular conjunctival discharge was assessed based on 0 (No evidence of discharge in conjunctiva) - 3 (Abundant quantity of mucopurulent or purulent discharge) scale. The study eye was defined as an eye with score of at least 1 for both ocular conjunctival discharge and bulbar conjunctival redness at baseline. Data analysis was performed in SHP640 and placebo reporting groups only but not in PVP-I 0.6%. | Day 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Bacterial Eradication Among Who Received SHP640 or Placebo on Day 5 | Bacterial eradication was defined as absence of all bacterial species present at or above pathological threshold at baseline in the study eye. Bacterial species were identified by Matrix Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry, using their unique protein patterns. Pathological threshold for individual bacterial species was based on colony-forming unit (CFU)/mL threshold levels established by Cagle and modified by Leibowitz for different ocular bacterial species found in the specimens collected from each participant. Data analysis was performed in SHP640 and placebo reporting groups only but not in PVP-I 0.6%. | Baseline, Day 5 | 
| Number of Participants With Clinical Resolution | Clinical resolution was defined as absence (score=0) of bulbar conjunctival injection and ocular conjunctival discharge in the study eye. Bulbar conjunctival injection was assessed based on 0 (Normal conjunctival vascular pattern) - 4 (Markedly prominent, intense diffuse hyperemia) scale which used pictures from VBR scale. Ocular conjunctival discharge was assessed based on 0 (No evidence of discharge in conjunctiva) - 3 (Abundant quantity of mucopurulent or purulent discharge) scale. The study eye was defined as an eye with score of atleast 1 for both ocular conjunctival discharge and bulbar conjunctival redness at baseline. | Day 3, 8 and 12 | 
| Number of Participants With Bacterial Eradication | Bacterial eradication was defined as absence of all bacterial species present at or above pathological threshold at baseline in the study eye. Bacterial species were identified by Matrix Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry, using their unique protein patterns. Pathological threshold for individual bacterial species was based on CFU/mL threshold levels established by Cagle and modified by Leibowitz for different ocular bacterial species found in the specimens collected from each participant. | Day 3, 8 and 12 | 
| Bulbar Conjunctival Injection Score | Bulbar conjunctival injection was assessed based on 0 (Normal conjunctival vascular pattern) - 4 (Markedly prominent, intense diffuse hyperemia) scale which used pictures from VBR scale. | Day 3, 5, 8 and 12 | 
| Change From Baseline in the Bulbar Conjunctival Injection Score | Bulbar conjunctival injection was assessed based on 0 (Normal conjunctival vascular pattern) - 4 (Markedly prominent, intense diffuse hyperemia) scale which used pictures from VBR scale. | Baseline, Day 3, 5, 8 and 12 | 
| Ocular Conjunctival Discharge Score | Ocular conjunctival discharge was assessed based on a 0 (No evidence of discharge in the conjunctiva) - 3 (Abundant quantity of mucopurulent or purulent discharge) scale. | Day 3, 5, 8 and 12 | 
| Change From Baseline in the Ocular Conjunctival Discharge Score | Ocular conjunctival discharge was assessed based on a 0 (No evidence of discharge in the conjunctiva) - 3 (Abundant quantity of mucopurulent or purulent discharge) scale. | Baseline, Day 3, 5, 8 and 12 | 
| Global Clinical Score | Global clinical score was defined as the sum of bulbar conjunctival injection and ocular conjunctival discharge scores. Bulbar conjunctival injection was assessed based on 0 (Normal conjunctival vascular pattern) - 4 (Markedly prominent, intense diffuse hyperemia) scale which used pictures from VBR scale. Ocular conjunctival discharge was assessed based on 0 (No evidence of discharge in conjunctiva) - 3 (Abundant quantity of mucopurulent or purulent discharge) scale. The study eye was defined as an eye with a score of at least 1 for both ocular conjunctival discharge and bulbar conjunctival redness at baseline. | Day 3, 5, 8 and 12 | 
| Change From Baseline in the Global Clinical Score | Global clinical score was defined as the sum of bulbar conjunctival injection and ocular conjunctival discharge scores. Bulbar conjunctival injection was assessed based on 0 (Normal conjunctival vascular pattern) - 4 (Markedly prominent, intense diffuse hyperemia) scale which used pictures from VBR scale. Ocular conjunctival discharge was assessed based on 0 (No evidence of discharge in conjunctiva) - 3 (Abundant quantity of mucopurulent or purulent discharge) scale. The study eye was defined as an eye with a score of at least 1 for both ocular conjunctival discharge and bulbar conjunctival redness at baseline. | Baseline, Day 3, 5, 8 and 12 | 
| Number of Participants With Modified Clinical Resolution | Modified clinical resolution was defined as a global clinical score of 0 or 1. Global clinical score was defined as the sum of bulbar conjunctival injection and ocular conjunctival discharge scores. Global clinical score was defined as the sum of bulbar conjunctival injection and ocular conjunctival discharge scores. Bulbar conjunctival injection was assessed based on 0 (Normal conjunctival vascular pattern) - 4 (Markedly prominent, intense diffuse hyperemia) scale which used pictures from VBR scale. Ocular conjunctival discharge was assessed based on 0 (No evidence of discharge in conjunctiva) - 3 (Abundant quantity of mucopurulent or purulent discharge) scale. | Day 3, 5, 8 and 12 | 
| Number of Participants With Expanded Clinical Resolution | Expanded clinical resolution was defined as a global clinical score of 0, 1, or 2 with neither injection nor discharge having a score of 2. Global clinical score was defined as the sum of bulbar conjunctival injection and ocular conjunctival discharge scores. Bulbar conjunctival injection was assessed based on 0 (Normal conjunctival vascular pattern) - 4 (Markedly prominent, intense diffuse hyperemia) scale which used pictures from VBR scale. Ocular conjunctival discharge was assessed based on 0 (No evidence of discharge in conjunctiva) - 3 (Abundant quantity of mucopurulent or purulent discharge) scale. | Day 3, 5, 8 and 12 | 
| Time to Clinical Resolution | Clinical resolution was defined as absence (score of 0) of bulbar conjunctival injection and ocular conjunctival discharge in the study eye. Bulbar conjunctival injection was assessed based on 0 (Normal conjunctival vascular pattern) - 4 (Markedly prominent, intense diffuse hyperemia) scale which used pictures from VBR scale. Ocular conjunctival discharge was assessed based on 0 (No evidence of discharge in conjunctiva) - 3 (Abundant quantity of mucopurulent or purulent discharge) scale. Time to clinical resolution defined as the date on which a participant first reached clinical resolution minus the date of first dose of investigational product, plus 1. | Baseline to Day 12 | 
| Number of Participants Who Used Rescue Medication | Rescue treatment with a licensed antibiotic according to the local standard of care was provided to participants if, in the judgment of the investigator, there was no clinical improvement or worsening of their condition to an extent that it would be in the best interest of the participant treated with an alternate therapy for safety reasons. | Baseline to Day 12 | 
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. Any AE that occured after the first dose of investigational product instillation was considered a TEAE. | From start of study drug administration up to 14 days |