Clinical trial NCT02998541: Treatment of Adenoviral Conjunctivitis With SHP640 Compared to Povidone-iodine (PVP-I) and Placebo
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Adenoviral Conjunctivitis
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2016-12-20
Enrollment: 219
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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:

  1. Report presence of signs and/or symptoms of adenoviral conjunctivitis for lesser than or equal to (\<=) 4 days prior to Visit 1
  2. Bulbar conjunctival injection: a grade of \>= 1 (mild) on a 0-4 Bulbar Conjunctival Injection Scale.
  3. 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:

  1. Have used an investigational product or device, or
  2. Have been enrolled in a clinical study (including vaccine studies) that, in the investigator's opinion, may impact this Shire-sponsored study

Primary outcomes:
measure: Number of Participants With Clinical Resolution Among Who Received SHP640 or Placebo on Day 6
timeFrame: Day 6
Secondary outcomes:
measure: Number of Participants With Clinical Resolution Among Who Received SHP640 or Povidone-Iodine (PVP-I) on Day 6
timeFrame: Day 6
measure: Number of Participants With Clinical Resolution Among Who Received Povidone-Iodine (PVP-I) or Placebo on Day 6
timeFrame: Day 6
measure: Number of Participants With Adenoviral Eradication Among Who Received Povidone-Iodine (PVP-I) or Placebo on Day 3
timeFrame: Day 3
measure: Number of Participants With Adenoviral Eradication Among Who Received SHP640 or Placebo on Day 6
timeFrame: Day 6
measure: Number of Participants With Adenoviral Eradication Among Who Received SHP640 or Povidone-Iodine (PVP-I) on Day 6
timeFrame: Day 6
measure: Percent Change From Baseline in Adenovirus Viral Titer as Assessed by Quantitative Polymerase Chain Reaction (qPCR) at Day 6 and 8
timeFrame: Day 6 and 8
measure: Number of Participants With Adenoviral Eradication on Day 8 and 12/Early Termination (ET)
timeFrame: Day 8 and 12/ET
measure: Number of Participants With Clinical Resolution on on Day 3, 8 and 12/Early Termination (ET)
timeFrame: Day 3, 8 and 12/ET
measure: Change From Baseline in Individual Clinical Signs Score at Day 3, 6, 8 and 12/Early Termination (ET)
timeFrame: Day 3, 6, 8 and 12/ET
measure: 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)
timeFrame: Day 3, 6, 8 and 12/ET
measure: Number of Participants With Modified Clinical Resolution on Day 3, 6, 8 and 12/Early Termination (ET)
timeFrame: Day 3, 6, 8 and 12/ET
measure: Number of Participants With Expanded Clinical Resolution on Day 3, 6, 8 and 12/Early Termination (ET)
timeFrame: Day 3, 6, 8 and 12/ET
measure: Number of Participants With Status of Cross-over Infection on Day 3, 6, 8 and 12/Early Termination (ET)
timeFrame: Day 3, 6, 8 and 12/ET
measure: Time to Clinical Resolution on Day 3, 6, 8 and 12/Early Termination (ET)
timeFrame: Day 3, 6, 8 and 12/ET
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs) of SHP640
timeFrame: From start of the study up to Day 14
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Arizona Eye Center
state: Arizona
city: Glendale
country: United States
facility: Midwestern University Eye Institute
state: Arizona
city: Prescott
country: United States
facility: M&M Eye Institute
state: Arizona
city: Sun City
country: United States
facility: Walman Eye Center
state: Arizona
city: Azusa
country: United States
facility: Milton M. Hom, OD, FAAO
state: California
city: Glendora
country: United States
facility: Mark B. Kislinger, MD, PhD, Inc.
state: California
city: Hemet
country: United States
facility: Inland Eye Specialists
state: California
city: Irvine
country: United States
facility: Lakeside Vision Center
state: California
city: Loma Linda
country: United States
facility: Loma Linda University
state: California
city: Long Beach
country: United States
facility: Eye Physicians of Long Beach
state: California
city: Los Angeles
country: United States
facility: Oxford Optical
state: California
city: Los Angeles
country: United States
facility: Macy Eye Center
state: California
city: Northridge
country: United States
facility: Shultz Chang Vision
state: California
city: Palo Alto
country: United States
facility: Stanford Byers Eye Institute
state: California
city: Petaluma
country: United States
facility: North Bay Eye Associates, Inc.
state: California
city: Poway
country: United States
facility: Arch Health Partners
state: California
city: Rancho Cordova
country: United States
facility: Martel Eye Medical Group
state: California
city: Redding
country: United States
facility: Shasta Eye Medical Group, Inc.
state: California
city: Bradenton
country: United States
facility: The Eye Associates
state: Florida
city: Fort Lauderdale
country: United States
facility: South Florida Vision Associates, LLC
state: Florida
city: Miami
country: United States
facility: Bascom Palmer Eye Institute
state: Florida
city: Miami
country: United States
facility: Lorites Medical Group
state: Florida
city: Orlando
country: United States
facility: Pediatric & Adult Research Center, LLC
state: Florida
city: Stuart
country: United States
facility: East Florida Eye Institute
state: Florida
city: Tamarac
country: United States
facility: Andrew Gardner Logan, MD / dba Logan Ophthalmic Research, LLC
state: Florida
city: Morrow
country: United States
facility: Eye Care Centers Management, Inc.
state: Georgia
city: Lake Villa
country: United States
facility: Jackson Eye
state: Illinois
city: Peoria
country: United States
facility: Illinois Eye Center
state: Illinois
city: Evansville
country: United States
facility: MediSphere Medical Research Center, an AMR affiliate
state: Indiana
city: Pittsburg
country: United States
facility: Kannarr Eye Care
state: Kansas
city: Lexington
country: United States
facility: Koffler Vision Group
state: Kentucky
city: Lexington
country: United States
facility: Kentucky Eye Institute
state: Kentucky
city: Louisville
country: United States
facility: Senior Health Services
state: Kentucky
city: Paducah
country: United States
facility: Baker, Carl W
state: Kentucky
city: Gretna
country: United States
facility: Lakeview Vision - Gretna
state: Louisiana
city: West Monroe
country: United States
facility: Haik Humble Eye Center
state: Louisiana
city: Bangor
country: United States
facility: Eye Center Northeast
state: Maine
city: Boston
country: United States
facility: Massachusetts Eye and Ear Infirmary
state: Massachusetts
city: Lexington
country: United States
facility: Shire Call Center
state: Massachusetts
city: Winchester
country: United States
facility: Clinical Eye Research of Boston
state: Massachusetts
city: Ann Arbor
country: United States
facility: The Regents of the University of Michigan
state: Michigan
city: Bloomington
country: United States
facility: Minnesota Eye Consultants, P.A.
state: Minnesota
city: Chesterfield
country: United States
facility: Lifelong Vision Foundation
state: Missouri
city: Kansas City
country: United States
facility: Moyes Eye Center
state: Missouri
city: Springfield
country: United States
facility: Mercy Research
state: Missouri
city: Las Vegas
country: United States
facility: Nevada Eye Care Professionals
state: Nevada
city: Berlin
country: United States
facility: Hassman Research Institute
state: New Jersey
city: South Orange
country: United States
facility: Northern New Jersey Eye Institute
state: New Jersey
city: Raleigh
country: United States
facility: Oculus Research
state: North Carolina
city: Winston-Salem
country: United States
facility: James Branch, M.D.
state: North Carolina
city: Doylestown
country: United States
facility: Matossian Eye Associates
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Eye Center
state: Pennsylvania
city: Wyomissing
country: United States
facility: Wyomissing Optometric Center
state: Pennsylvania
city: Rapid City
country: United States
facility: Black Hills Regional Eye Institute
state: South Dakota
city: Memphis
country: United States
facility: The Eye Center at Southern College of Optometry
state: Tennessee
city: Memphis
country: United States
facility: Total Eye Care, PA
state: Tennessee
city: Memphis
country: United States
facility: Eye Specialty Group
state: Tennessee
city: Nashville
country: United States
facility: Nashville Vision Associates
state: Tennessee
city: Nashville
country: United States
facility: Toyos Clinic
state: Tennessee
city: Houston
country: United States
facility: Houston Eye Associates
state: Texas
city: Lakeway
country: United States
facility: Lake Travis Eye & Laser Center
state: Texas
city: League City
country: United States
facility: Houston Eye Associates
state: Texas
city: Mission
country: United States
facility: DCT-Shah Research, LLC dba Discovery Clinical Trials
state: Texas
city: San Antonio
country: United States
facility: R and R Eye Research, LLC.
state: Texas
city: Sugar Land
country: United States
facility: Lone Star Eye Care, P.A.
state: Texas
city: Clinton
country: United States
facility: Ericksen Research & Development, LLC
state: Utah
city: Falls Church
country: United States
facility: Emerson Clinical Research Institute, LLC
state: Virginia
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Sippy Downs
country: Australia
facility: University of the Sunshine Coast Clinical Trials Centre
state: Queensland
city: Linz
country: Austria
facility: Kepler Universitätsklinikum
city: Vienna
country: Austria
facility: AKH - Medizinische Universitaet Wien
city: Vienna
country: Austria
facility: Vienna Institute for Research in Ocular Surgery
city: Ottawa
country: Canada
facility: The Ottawa Hospital - General Campus, University of Ottawa Eye Institute
state: Ontario
city: Waterloo
country: Canada
facility: University of Waterloo School of Optometry and Vision Science
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Centre/Glen Site / Royal Victoria Hospital
state: Quebec
city: Tallinn
country: Estonia
facility: Eye Clinic Dr Kirsta Turman
city: Tallinn
country: Estonia
facility: East Tallinn Central Hospital
city: Tartu
country: Estonia
facility: Tartu University Hospital
city: Limoges
country: France
facility: CHU Limoges - Hopital Dupuytren
state: Haute Vienne
city: Paris
country: France
facility: Hopital Necker - Enfants Malades
city: Mainz
country: Germany
facility: Klinisches Studienzentrum der Augenklinik
city: Muenster
country: Germany
facility: Augenärzte am Franziskus Hospital
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
state: Csongrad
city: Gyongyos
country: Hungary
facility: Bugat Pal Korhaz
state: Heves
city: Debrecen
country: Hungary
facility: Debreceni Egyetem
city: Kaposvár
country: Hungary
facility: Somogy Megyei Kaposi Mor Oktato Korhaz
city: Veszprem
country: Hungary
facility: Csolnoky Ferenc Korhaz
city: Hyderabad
country: India
facility: L. V. Prasad Eye Institute
state: Andhra Pradesh
city: Bangalore
country: India
facility: Sankara Eye Hospital
state: Karnataka
city: Bangalore
country: India
facility: Bhagwan Mahaveer Jain Hospital
state: Karnataka
city: Bangalore
country: India
facility: M. S. Ramaiah Medical College and Hospital
state: Karnataka
city: Bangalore
country: India
facility: Sapthagiri Hospital
state: Karnataka
city: Belgaum
country: India
facility: K.L.E. Society's Dr. Prabhakar Kore Hospital and Medical Research Centre
state: Karnataka
city: Nagpur
country: India
facility: NKP Salve Institute of Medical Sciences
state: Maharashtra
city: Navi Mumbai
country: India
facility: Dr. D. Y. Patil Medical College
state: Maharashtra
city: Pune
country: India
facility: PBMA'S H. V. Desai Eye Hospital
state: Maharashtra
city: Bikaner
country: India
facility: S. P. Medical College & Associated Group of Hospitals
state: Rajasthan
city: Noida
country: India
facility: ICARE Eye Hospital and Post Graduate Institute
state: Uttar Pradesh
city: Kolkata
country: India
facility: Regional Institute of Ophthalmology
state: West Bengal
city: Afula
country: Israel
facility: HaEmek Medical Center
city: Beer Sheva
country: Israel
facility: Soroka University Medical Center
city: Haifa
country: Israel
facility: Rambam MC
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Petah Tikva
country: Israel
facility: Rabin Medical Center-Beilinson Campus
city: Rehovot
country: Israel
facility: Kaplan Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Bologna
country: Italy
facility: A.O.U. Policlinico San'Orsola-Malpighi
city: La Libertad
country: Peru
facility: Instituto Regional de Oftalmología
city: Lima
country: Peru
facility: Macula D&T S.R.L.
city: Lima
country: Peru
facility: Oftalmosalud SRL.
city: Bytom
country: Poland
facility: Szpital Specjalistyczny nr 1
city: Krakow
country: Poland
facility: Centrum Medyczne UNO-MED
city: Olsztyn
country: Poland
facility: Centrum Diagnostyki i Mikrochirurgii Oka LENS
city: Tarnów
country: Poland
facility: Centrum Medyczne Uno-Med (Private Practice)
city: Warszawa
country: Poland
facility: Retina Sp. z o.o.
city: Johannesburg
country: South Africa
facility: Newtown Clinical Research
state: Gauteng
city: Pretoria
country: South Africa
facility: Into Research
state: Gauteng
city: Pretoria
country: South Africa
facility: Pretoria Eye Institute Research Foundation
state: Gauteng
city: Durban
country: South Africa
facility: Nelson R Mandela School of Medicine Ophthalmology Department
state: KwaZulu-Natal
city: Oviedo
country: Spain
facility: Instituto Oftalmológico Fernández-Vega
state: Asturias
city: Burgos
country: Spain
facility: Complejo Asistencial Universitario de Burgos
city: Girona
country: Spain
facility: Hospital Universitari de Girona Dr Josep Trueta
city: Huelva
country: Spain
facility: Clinica Oftalmologia Gil Piña
city: Madrid
country: Spain
facility: Clinica Rementeria
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro Majadahonda
city: Sevilla
country: Spain
facility: Cartuja Vision
city: Valencia
country: Spain
facility: FISABIO-Oftalmología Médica
city: Zaragoza
country: Spain
facility: Hospital Clinico Universitario Lozano Blesa
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Manchester
country: United Kingdom
facility: Manchester Royal Eye Hospital
state: Greater Manchester
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: