Treatment of Adenoviral Conjunctivitis With SHP640 Compared to Povidone-iodine (PVP-I) 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 adenoviral 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 PVP-Iodine and Placebo in the Treatment of Adenoviral Conjunctivitis

Conditions
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Adenoviral Conjunctivitis

Intervention / Treatment
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* Drug: SHP640
* Drug: PVP-I 0.6%
* Other: 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 lesser than (<) 3 months of age at Visit 1 must have been full-term, i.e. greater than or equal to (>=) 37 weeks gestational age at birth). Meet at least 1 of the 2 criteria below: a) Have a positive AdenoPlus test at Visit 1 in at least 1 eye. b) Have at least 2 of the following 5 criteria, based upon medical history and examination: i.Symptoms within the past 7 days consistent with acute upper respiratory tract infection (eg. sore throat, cough, rhinorrhea, etc). ii. Contact within the past 7 days with family members or other individuals with recent onset of symptoms consistent with conjunctivitis iii. Acute onset within the past 4 days of one or more of the following ocular symptoms: burning/irritation, foreign body sensation, light sensitivity. iv. Enlarged periauricular lymph node(s). v. Presence of follicles on tarsal conjunctiva. Note:If the participant only meets Inclusion Criterion (a positive AdenoPlus test in at least 1 eye), then the same eye must meet the mentioned below Inclusion Criterion. Have a clinical diagnosis of suspected adenoviral 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 adenoviral conjunctivitis for lesser than or equal to (<=) 4 days prior to Visit 1 Bulbar conjunctival injection: a grade of >= 1 (mild) on a 0-4 Bulbar Conjunctival Injection Scale. Watery conjunctival discharge: a grade of >= 1 (mild) on a 0-3 Watery 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 the 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 participants 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 pre-planned overnight hospitalization during the period of the study. Have presence of any intraocular, corneal, or conjunctival ocular inflammation (eg, uveitis, iritis, ulcerative keratitis, chronic blepharoconjunctivitis), other than adenoviral conjunctivitis. Have presence of corneal subepithelial infiltrates at Visit 1. Have active or 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-adenoviral ocular infection (e.g. bacterial, 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 (i.e. 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 (i.e. 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 (e.g. 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 which requires invasive treatment (e.g. intravitreal treatment with VEGF inhibitors or corticosteroids) and may progress during the study participation period. Have used any topical ocular or systemic anti-vials or antibiotics within <= 7 days of enrollment. Have used any topical ocular Non-steroidal Anti-inflammataory Drugs (NSAIDs) 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 peri-ocular 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 the 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 (antihepatitis 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 receive one drop of SHP640 (0.1 percent [%] dexamethasone and 0.6% PVP-I) ophthalmic suspension in each eye 4 times daily (QID) for 7 days. | Drug: SHP640<br>* Participants will receive one drop of SHP640 (0.1 % dexamethasone and 0.6% PVP-I) ophthalmic suspension in each eye QID (with a minimum of 2 hours between doses) for 7 days.<br>* Other names: FST-100;|
| Active Comparator: PVP-I 0.6%<br>Participants will receive one drop of 0.6% PVP-I ophthalmic solution in each eye QID for 7 days. | Drug: PVP-I 0.6%<br>* Participants will receive one drop of PVP-I ophthalmic solution in each eye QID (with a minimum of 2 hours between doses) for 7 days.<br>|
| Placebo Comparator: Placebo<br>Participants will receive one drop of placebo ophthalmic solution in each eye QID for 7 days. | Other: Placebo<br>* Participants will receive one drop of placebo ophthalmic solution in each eye 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 6 | Clinical resolution of adenoviral conjunctivitis was defined as the absence (score=0) of bulbar conjunctival injection and watery conjunctival discharge in the study eye. The study eye was defined based on participant's bulbar conjunctival redness and watery conjunctival discharge scores at baseline as well as his/her cell culture-immunofluorescence assay (CC-IFA) results at baseline. Bulbar conjunctival injection was assessed based on a 0 (Normal conjunctival vascular pattern)-4 (Markedly prominent, intense diffuse hyperemia) scale which used pictures from the validated bulbar redness (VBR) scale. Watery conjunctival discharge was assessed based on a 0-3 scale (0 - None and 3 - Severe: Abundant quantity of watery discharge observed in the lower conjunctival fornix and in the lower lid margin). Higher score represent worse symptoms for both scores. Data analysis was performed in SHP640 and placebo reporting groups only but not in PVP-I 0.6%. | Day 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Clinical Resolution Among Who Received SHP640 or Povidone-Iodine (PVP-I) on Day 6 | Clinical resolution of adenoviral conjunctivitis was defined as the absence (score=0) of bulbar conjunctival injection and watery conjunctival discharge in the study eye. The study eye was defined based on participant's bulbar conjunctival redness and watery conjunctival discharge scores at baseline as well as his/her CC-IFA results at baseline. Bulbar conjunctival injection was assessed based on a 0 (Normal conjunctival vascular pattern)-4 (Markedly prominent, intense diffuse hyperemia) scale which used pictures from the validated bulbar redness (VBR) scale. Watery conjunctival discharge was assessed based on a 0-3 scale (0 - None and 3 - Severe: Abundant quantity of watery discharge observed in the lower conjunctival fornix and in the lower lid margin). Higher score represent worse symptoms for both scores. Data analysis was performed in SHP640 and PVP-I 0.6% reporting groups only but not in placebo. | Day 6 | 
| Number of Participants With Clinical Resolution Among Who Received Povidone-Iodine (PVP-I) or Placebo on Day 6 | Clinical resolution of adenoviral conjunctivitis was defined as the absence (score=0) of bulbar conjunctival injection and watery conjunctival discharge in the study eye. The study eye was defined based on participant's bulbar conjunctival redness and watery conjunctival discharge scores at baseline as well as his/her CC-IFA results at baseline. Bulbar conjunctival injection was assessed based on a 0 (Normal conjunctival vascular pattern)-4 (Markedly prominent, intense diffuse hyperemia) scale which used pictures from the validated bulbar redness (VBR) scale. Watery conjunctival discharge was assessed based on a 0-3 scale (0 - None and 3 - Severe: Abundant quantity of watery discharge observed in the lower conjunctival fornix and in the lower lid margin). Higher score represent worse symptoms for both scores. Data analysis was performed in PVP-I 0.6% and placebo reporting groups only but not in SHP640. | Day 6 | 
| Number of Participants With Adenoviral Eradication Among Who Received Povidone-Iodine (PVP-I) or Placebo on Day 3 | Adenoviral eradication for the study eye was defined as negative Cell Culture- Immunofluorescence Assay (CC-IFA) in that eye. CC-IFA for each eye was conducted using conjunctival swab samples collected at each visit to determine the presence of adenovirus. The study eye was defined based on participants bulbar conjunctival redness and watery conjunctival discharge scores at baseline as well as his/her CC-IFA results at baseline. Data analysis was performed in PVP-I 0.6% and placebo reporting groups only but not in SHP640. | Day 3 | 
| Number of Participants With Adenoviral Eradication Among Who Received SHP640 or Placebo on Day 6 | Adenoviral eradication for the study eye was defined as negative CC-IFA in that eye. CC-IFA for each eye was conducted using conjunctival swab samples collected at each visit to determine the presence of adenovirus. The study eye was defined based on participant's bulbar conjunctival redness and watery conjunctival discharge scores at baseline as well as his/her CC-IFA results at baseline. Data analysis was performed in SHP640 and placebo reporting groups only but not in PVP-I 0.6%. | Day 6 | 
| Number of Participants With Adenoviral Eradication Among Who Received SHP640 or Povidone-Iodine (PVP-I) on Day 6 | Adenoviral eradication for the study eye was defined as negative CC-IFA in that eye. CC-IFA for each eye was conducted using conjunctival swab samples collected at each visit to determine the presence of adenovirus. The study eye was defined based on participants bulbar conjunctival redness and watery conjunctival discharge scores at baseline as well as his/her CC-IFA results at baseline. Data analysis was performed in SHP640 and PVP-I 0.6% reporting groups only but not in placebo. | Day 6 | 
| Percent Change From Baseline in Adenovirus Viral Titer as Assessed by Quantitative Polymerase Chain Reaction (qPCR) at Day 6 and 8 | qPCR test was performed on all CC-IFA positive samples at all visits to determine viral count in the study eye. The study eye was defined based on participants bulbar conjunctival redness and watery conjunctival discharge scores at baseline as well as his/her CC-IFA results at baseline. Percent (%) change from baseline in adenovirus viral titer as assessed by qPCR was reported. | Day 6 and 8 | 
| Number of Participants With Adenoviral Eradication on Day 8 and 12/Early Termination (ET) | Adenoviral eradication for the study eye was defined as negative CC-IFA in that eye. CC-IFA for each eye was conducted using conjunctival swab samples collected at each visit to determine the presence of adenovirus. The study eye was defined based on participants bulbar conjunctival redness and watery conjunctival discharge scores at baseline as well as his/her CC-IFA results at baseline. | Day 8 and 12/ET | 
| Number of Participants With Clinical Resolution on on Day 3, 8 and 12/Early Termination (ET) | Clinical resolution of adenoviral conjunctivitis was defined as the absence (score=0) of bulbar conjunctival injection and watery conjunctival discharge in the study eye. The study eye was defined based on participant's bulbar conjunctival redness and watery conjunctival discharge scores at baseline as well as his/her CC-IFA results at baseline. Bulbar conjunctival injection was assessed based on a 0 (Normal conjunctival vascular pattern)-4 (Markedly prominent, intense diffuse hyperemia) scale which used pictures from the validated bulbar redness (VBR) scale. Watery conjunctival discharge was assessed based on a 0-3 scale (0 - None and 3 - Severe: Abundant quantity of watery discharge observed in the lower conjunctival fornix and in the lower lid margin). Higher score represent worse symptoms for both scores. | Day 3, 8 and 12/ET | 
| Change From Baseline in Individual Clinical Signs Score at Day 3, 6, 8 and 12/Early Termination (ET) | The Individual clinical signs score (bulbar conjunctival injection and watery conjunctival discharge) in the study were reported. The study eye was defined based on participants bulbar conjunctival redness and watery conjunctival discharge scores at baseline as well as his/her CCIFA results at baseline. | Day 3, 6, 8 and 12/ET | 
| Number of Participants With at Least 2 Point Reduction From Baseline in the Global Clinical Score at Day 3, 6, 8 and 12/Early Termination (ET) | Global clinical score was the sum of bulbar conjunctival injection and watery conjunctival discharge. The study eye was defined based on participants bulbar conjunctival redness and watery conjunctival discharge scores at baseline as well as his/her CC-IFA results at baseline. | Day 3, 6, 8 and 12/ET | 
| Number of Participants With Modified Clinical Resolution on Day 3, 6, 8 and 12/Early Termination (ET) | Modified clinical resolution was defined as a global clinical score of 0 or 1. Global clinical score was the sum of bulbar conjunctival injection and watery conjunctival discharge. The study eyewas defined based on participants bulbar conjunctival redness and watery conjunctival discharge scores at baseline as well as his/her CC-IFA results at baseline. | Day 3, 6, 8 and 12/ET | 
| Number of Participants With Expanded Clinical Resolution on Day 3, 6, 8 and 12/Early Termination (ET) | 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 the sum of bulbar conjunctival injection and watery conjunctival discharge. The study eye was defined based on participants bulbar conjunctival redness and watery conjunctival discharge scores at baseline as well as his/her CC-IFA results at baseline. | Day 3, 6, 8 and 12/ET | 
| Number of Participants With Status of Cross-over Infection on Day 3, 6, 8 and 12/Early Termination (ET) | Number of participants with status of cross-over infection to a participant's fellow eye. Participants with only 1 infected eye at baseline were reported. | Day 3, 6, 8 and 12/ET | 
| Time to Clinical Resolution on Day 3, 6, 8 and 12/Early Termination (ET) | Time to clinical resolution were reported based on the assessments in the study eye. | Day 3, 6, 8 and 12/ET | 
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs) of SHP640 | 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. A SAE was any untoward medical occurrence (whether considered to be related to investigational product or not) that at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital abnormality/birth defect, is an important medical event. Any AE that occured after the first dose of IP instillation was considered a TEAE. | From start of the study up to Day 14 |