Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12619000177156
Ethics application status
Approved
Date submitted
29/01/2019
Date registered
6/02/2019
Date last updated
5/02/2020
Date data sharing statement initially provided
6/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
OKG-0301 for the Treatment of Acute Adenoviral Conjunctivitis
Scientific title
A Phase 2, Multi-centeR, Randomized, DoUBle-Masked, Placebo-Controlled StudY to Evaluate the Clinical Safety and Efficacy of OKG-0301 in the Treatment of Acute Adenoviral Conjunctivitis (RUBY)
Secondary ID [1] 296239 0
None
Universal Trial Number (UTN)
U1111-1221-5795
Trial acronym
RUBY
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Adenoviral Conjunctivitis 309879 0
Infectious Conjunctivitis 309881 0
Viral Conjunctivitis 309882 0
Condition category
Condition code
Eye 308672 308672 0 0
Diseases / disorders of the eye
Infection 309943 309943 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
OKG-0301 (either 0.012% or 0.03%), a preserved ophthalmic solution containing Ranpirnase, will be instilled as a topical eye drop, 4 times per day for 5 days. Patients will be randomized in accordance with a predefined block randomization schedule based, in part, on site of presentation. Patients will also be required to complete a diary to document adherence to dosing schedule. This diary will be reviewed with the Investigators at each visit.
Intervention code [1] 312565 0
Treatment: Drugs
Comparator / control treatment
Vehicle ophthalmic solution will serve as a masked comparator.
Control group
Placebo

Outcomes
Primary outcome [1] 307638 0
Mean change from baseline in viral titre levels in the study eye at Visit 3. Viral titre levels are assessed by a quantitative viral plaque-forming unit (PFU) assay used to measure the amount of infectious virus. This cell culture based technique is considered the gold standard for quantifying the "living" viral burden and will be determined from individual eye swabs.
Timepoint [1] 307638 0
Visit 3 (Day 7 +/- 1 day)
Secondary outcome [1] 352467 0
Global clinical cure of acute adenoviral conjunctivitis in the study eye as measured by the absence (score = 0) of the sum of the scores using the referenced scales for watery conjunctival discharge (graded on a scale of 0-3 based on severity, developed specifically for this trial) and bulbar conjunctival redness (graded using the validated Ora Calibra Scale 16.2: Bulbar Conjunctival Redness Grading Scale)
Timepoint [1] 352467 0
Visits 2, 3 & 4 (Days 4 +/-1d, 7 +/-1d, & 14 +/-1d, respectively) with visit 1 (Day 1) being the enrolment date and initiation of treatment
Secondary outcome [2] 352468 0
Adenoviral eradication assessed by cell culture immunofluorescence assay (CC-IFA) determined from the eye swab taken at each visit.
Timepoint [2] 352468 0
Visits 2, 3 & 4 (Days 4 +/-1d, 7 +/-1d, & 14 +/-1d, respectively) with visit 1 (Day 1) being the enrolment date and initiation of treatment
Secondary outcome [3] 352469 0
Presence and severity of subepithelial infiltrates assessed under slit lamp exam with Investigator grading on a semi-quantitative scale.
Timepoint [3] 352469 0
Visits 2, 3 & 4 (Days 4 +/-1d, 7 +/-1d, & 14 +/-1d, respectively) with visit 1 (Day 1) being the enrolment date and initiation of treatment
Secondary outcome [4] 352470 0
The rate of cross-over infection to a patient’s fellow eye will be assessed for patients presenting at Visit 1 with only single eye infection based on clinical signs and symptoms. If fellow eye presents during visits 2, 3 or 4 based on clinical signs and symptoms, adenoviral presence will be confirmed using the AdenoPlus diagnostic.
Timepoint [4] 352470 0
Visits 2, 3 & 4 (Days 4 +/-1d, 7 +/-1d, & 14 +/-1d, respectively) with visit 1 (Day 1) being the enrolment date and initiation of treatment
Secondary outcome [5] 366281 0
Safety measures will be assessed at each visit using Slit Lamp biomicroscopy (non-dilated fundus examination), BSCVA, Adverse events (AEs), and tolerability by assessment of drop comfort in the fellow eye at Visit 1 by the patient upon instillation (self-administered), at 5 minutes after instillation using visual analog scales.
Timepoint [5] 366281 0
Visits 2, 3 & 4 (Days 4 +/-1d, 7 +/-1d, & 14 +/-1d, respectively) with visit 1 (Day 1) being the enrolment date and initiation of treatment

Eligibility
Key inclusion criteria
Each patient MUST:
1. Be willing and able to provide informed consent either written, or if the patient is not able to read, provide consent as stipulated by local laws and Human Research Ethics Committee (HREC) guidelines.
2. Be willing and able to follow all instructions and attend all study visits.
3. Have a clinical diagnosis of suspected acute adenoviral conjunctivitis in at least 1 eye and the presence of both of the following minimal clinical signs in that same eye:
• Bulbar conjunctival redness: a minimum grade of ‘1’ on 0-3 scale
• Watery ocular discharge: a minimum grade of ‘1’ on a 0-3 scale
4. Patient reported presence of signs and symptoms consistent with adenoviral conjunctivitis equal to or less than 3 days in same eye prior to Visit 1.
5. Have a positive AdenoPlus® test at Visit 1 in the same eye that meets the minimum 1+ grade for bulbar conjunctival redness and watery ocular discharge.
6. Be willing to discontinue contact lens wear for the duration of the study.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Each patient MUST NOT:
1. Have known sensitivity or poor tolerance to any component of the study medications or diagnostics.
2. Have a history of ocular surgical intervention or trauma within 12 weeks prior to Visit 1 or planned for the period of the study.
3. Have presence of any active ocular inflammation (e.g., uveitis, allergic conjunctivitis, ocular rosacea, or iritis), other than acute adenoviral conjunctivitis.
4. Have clinical signs or presence of an ocular infection other than acute adenoviral conjunctivitis (e.g., bacterial, fungal or other ocular viral infection, such as herpes).
5. Have the presence of corneal subepithelial infiltrates at baseline.
6. Have a history of recurrent corneal erosion syndrome, ulcerative keratitis or dry eye, including meibomian gland dysfunction and other ocular surface diseases.
7. Have presence of blepharitis, lid abnormality, significant inflammation of the lid margin, or ptosis.
8. Have lacrimal duct obstruction in either eye.
9. Have presence of any other clinically significant findings during the slit lamp exam that may interfere with study parameters or otherwise confound the data as determined by the investigator
10. Have any clinically significant retinal or optic nerve findings (as observed in the non-dilated fundus exam) or prior diagnoses in either eye that may interfere with study parameters or otherwise confound the data as determined by the investigator).
11. Have used any topical ocular or systemic anti-viral or topical ocular or systemic corticosteroid within 7 days of enrollment and do not plan to start any topical ocular or systemic anti-viral during study duration. Inhaled, intranasal, and topical dermatologic steroids (except on the face) are allowed during the study.
12. Initiate or continue the use of warm or cold compresses for the duration of the trial.
13. Have used any topical ophthalmic solutions, including tear substitutes and diagnostics, within 2 hours of Visit 1 and be unable to discontinue all topical ophthalmic solutions (including diagnostics, except as required by this protocol and antibiotics) for the duration of the study. In addition, if the patient has used an artificial tear or other topical ophthalmic formulated in a hydrogel within the past 72 hours.
14. Be currently pregnant, nursing, or planning a pregnancy; or be a woman that has a positive pregnancy test.
15. Have any uncontrolled (not on a stable regimen for the past 30 days) systemic disease or debilitating disease (e.g., cardiovascular disease, hypertension, diabetes, or cystic fibrosis) or taking medications known to impact the ocular surface and/or tear film.
16. Have a planned overnight hospitalization during the period of the study.
17. Have any uncontrolled (not on a stable regimen for the past 30 days) autoimmune disease or taking medications known to impact the ocular surface and/or tear film.
18. Have prior (within 30 days of beginning study treatment) or anticipated concurrent use of an investigational drug or device.
19. Have a condition or a situation which, in the investigator’s opinion, may put the patient at increased risk, confound study data, or interfere significantly with the patient’s study participation.
20. Be unlikely to follow study instructions or to complete all required study visits or has a condition or situation that in the investigator's opinion, may put the patient at significant risk, may confound the study results, or may interfere significantly with the patient's participation in the study

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by phone/fax/computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Summaries for continuous variables will include the sample size, mean, standard deviation, median, minimum, and maximum. Summaries for discrete variables will include frequencies and percentages. In general, data will be summarized by treatment group and overall actively treated patients.
Differences between treatment groups will be calculated as Test – Vehicle and change from baseline will be calculated as follow-up visit – baseline. The baseline visit will be defined as the last non-missing measure prior to initiation of investigational treatment. All efficacy analyses will use a 2-sided alpha = 0.05 test unless otherwise stated.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
11/02/2019
Actual
Date of last participant enrolment
Anticipated
30/06/2020
Actual
Date of last data collection
Anticipated
15/07/2020
Actual
Sample size
Target
219
Accrual to date
0
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,WA,VIC
Recruitment hospital [1] 12066 0
Sydney Hospital and Sydney Eye Hospital - Sydney
Recruitment hospital [2] 12070 0
The Royal Victorian Eye and Ear Hospital - East Melbourne
Recruitment hospital [3] 12071 0
Lions Eye Institute Day Surgery Centre - Nedlands
Recruitment hospital [4] 12072 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [5] 13056 0
Hobart Eye Surgeons - Hobart
Recruitment hospital [6] 13057 0
Albury Eye Clinic - Albury
Recruitment hospital [7] 15799 0
Casey Hospital - Berwick
Recruitment postcode(s) [1] 24225 0
2000 - Sydney
Recruitment postcode(s) [2] 24230 0
3002 - East Melbourne
Recruitment postcode(s) [3] 24231 0
6009 - Nedlands
Recruitment postcode(s) [4] 24232 0
5000 - Adelaide
Recruitment postcode(s) [5] 25564 0
7000 - Hobart
Recruitment postcode(s) [6] 25565 0
2640 - Albury
Recruitment postcode(s) [7] 29233 0
3806 - Berwick

Funding & Sponsors
Funding source category [1] 300837 0
Commercial sector/Industry
Name [1] 300837 0
Okogen Pty Ltd
Country [1] 300837 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Okogen Pty Ltd
Address
31 Queen St, 9th Fl
Melbourne VIC 3000
Country
Australia
Secondary sponsor category [1] 300382 0
None
Name [1] 300382 0
None
Address [1] 300382 0
None
Country [1] 300382 0
Other collaborator category [1] 280377 0
Commercial sector/Industry
Name [1] 280377 0
Ora Clinical Research Pty Ltd
Address [1] 280377 0
40-42 Scott Street
Dandong, Victoria 3175
Country [1] 280377 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301606 0
St Vincent's Hospital Melbourne Human Research Ethics Committee
Ethics committee address [1] 301606 0
41 Victoria Parade
Fitzroy VIC 3065
Ethics committee country [1] 301606 0
Australia
Date submitted for ethics approval [1] 301606 0
23/10/2018
Approval date [1] 301606 0
18/12/2018
Ethics approval number [1] 301606 0
47911

Summary
Brief summary
Acute adenoviral conjunctivitis is a highly contagious, widespread endemic disease associated with frequent outbreaks, significant patient discomfort, lost productivity, and in some cases permanent visual compromise from long-term immune mediated sequelae. OKG-0301 is a novel ophthalmic solution with a potent ribonuclease that has broad-spectrum antiviral properties relevant for the treatment of acute adenoviral conjunctivitis. This randomized, double masked, multi-center Phase 2 study is being conducted entirely within Australia and is designed to support the safety and efficacy of OKG-0301 for the treatment of acute adenoviral conjunctivitis. The study intends to show superiority of OKG-0301 Ophthalmic Solution compared to vehicle for the primary efficacy endpoint of mean change from baseline in viral titre in patients with acute adenoviral conjunctivitis. Secondary efficacy endpoints including adenoviral eradication, clinical cure of acute adenoviral conjunctivitis, subepithelial infiltrates, other clinical signs and symptoms, and rate of cross-over infection to the other eye will also be assessed. Safety will also be evaluated.
Trial website
www.rubytrial.com.au
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 87534 0
Prof Stephanie Watson
Address 87534 0
Sydney Eye Hospital, Save Sight Institute
8 Macquarie St,
Sydney NSW 2000,
Country 87534 0
Australia
Phone 87534 0
+61 2 9382 7111
Fax 87534 0
Email 87534 0
[email protected]
Contact person for public queries
Name 87535 0
Dr Eric Daniels
Address 87535 0
Okogen Pty Ltd
31 Queen St, Level 9
Melbourne VIC 3000
Country 87535 0
Australia
Phone 87535 0
+61 448 787 315
Fax 87535 0
Email 87535 0
[email protected]
Contact person for scientific queries
Name 87536 0
Dr Eric Daniels
Address 87536 0
Okogen Pty Ltd
31 Queen St, Level 9
Melbourne VIC 3000
Country 87536 0
Australia
Phone 87536 0
+61 448 787 315
Fax 87536 0
Email 87536 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.