Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001113741
Ethics application status
Approved
Date submitted
6/08/2022
Date registered
12/08/2022
Date last updated
28/09/2023
Date data sharing statement initially provided
12/08/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
A first in human safety study of ETX-4143 (a topical cooling device for the eye) in subjects with chronic eye pain
Scientific title
An adaptive, early-feasibility, open-label, pilot clinical study of ETX-4143 in subjects with chronic ocular pain
Secondary ID [1] 307625 0
ETX4143-A001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
chronic ocular pain 327108 0
Condition category
Condition code
Eye 324256 324256 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The ETX-4143 2.0 Device is a handheld medical device that contains an internal frozen (-20° Centigrade) mixture of purified water and glycerol; ETX-4143 2.0 Device does not contain an active pharmaceutical ingredient. It is applied topically to the scleral surface, following instillation of topical anesthetic drops and placement of a speculum and cornea shield. It is provided in disposable, single-use packaging. The investigational product will be administered to up to 16 (sixteen) subjects meeting the criteria for chronic ocular pain and all protocol inclusion/exclusion criteria by a qualified physician.

The duration of the ETX4143 application/exposure is dependent on the subject's chronological position during the enrollment process. There are 4 cohorts which are enrolled sequentially: Cohort A--4 subjects will have application of device for 30 seconds; Cohort B--4 subjects will have application of device for 2 minutes; Cohort C--4 subjects will have application of device for 6 minutes; Cohort D--4 subjects will have application of device for 10 minutes. The treatment time is dependent on the subject's assigned cohort.

There will be a pause between enrollment of each Cohort to allow review by the Data Safety Monitor. The DSM will review one week cumulative safety date for each cohort before making recommendation for the study to progress or not to the next cohort. Subsequent subject information will be reviewed by the DSM minimally on a quarterly basis. However, the Medical Monitor will review data on a continuous basis.

The study extends to a total of 8 visits over 8 weeks. Each visit is anticipated to last approximately 2 hours. The investigational device will be applied at the investigator's clinic on Day 0/Visit 2. Subsequent visits are: the screening visit/Visit 1; post-procedure day 1/Visit 3; post-procedure visits week 1-4, and 8/Visits 4-7, and 8. There is no wash out period for any previously prescribed treatment/medication. Subjects will be provided with a post procedure information sheet that has been developed by the sponsor of this study, EyeCool Therapeutics.
Intervention code [1] 324075 0
Treatment: Devices
Comparator / control treatment
none
Control group
Uncontrolled

Outcomes
Primary outcome [1] 332070 0
The primary endpoint is safety and tolerability of ETX-4143. Assessments/evaluations will be utilized at visits 2-8 to evaluate potential safety risks of local irritation or foreign body sensation, development of corneal edema, endothelial cell loss, ocular hypo- or hypertension, increased vagal tone from stimulation of the oculi-cardiac reflex, corneal epithelial defects, infection, uveitis, or inflammation , and allergic reaction. A composite of the below test/assessments will be utilized to support the primary outcome. Assessments/evaluations utilized at visits 2-8 include:
• Best Corrected Visual Acuity (BCVA) at screening, post-procedure day 1, week 1-4, and week 8
• Intra-ocular Pressure (IOP) (using Goldmann, Tonopen, iCare, or other applanation or rebound method) at screening, post-procedure day 1, week 1-4, and week 8
• Slit-lamp evaluation at screening to assess for abnormalities of the epithelial surface at post-procedure day 1, week 1-4, and week 8
• Specular Microscopy at screening to assess epithelial cell density at week 4 and week 8
• Adverse event (AE) query (reported, elicited, and observed) at screening visit, post-procedure day 1, week 1-4, and week 8 visits
Timepoint [1] 332070 0
Visit 8 / Week 8 will be the primary timepoint. However, data will be collected regarding this timepoints from Day 0/ screening visit through week 8 visit/ Visit 8

• Best Corrected Visual Acuity (BCVA) at screening, post-procedure day 1, week 1-4, and week 8
• Intra-ocular Pressure (IOP) (using Goldmann, Tonopen, iCare, or other applanation or rebound method) at screening (V1), post-procedure day 1 (V3), post-procedure week 1-4 (V4-7), and post-procedure week 8 (V8)
• Slit-lamp evaluation at screening (V1), post-procedure day 1 (V3), post-procedure week 1-4 (V4-7), and post-procedure week 8 (V8)
• Specular Microscopy at screening (V1), post-procedure week 4 (V7), and post-procedure week 8 (V8) 8
• Adverse event (AE) query (reported, elicited, and observed) at screening (V1), procedure day (V2), post-procedure day 1 (V3), post-procedure week 1-4 (V4-7), and post-procedure week 8 (V8)
Secondary outcome [1] 412056 0
1) Corneal sensitivity: Change in central corneal sensitivity will be evaluated using a Cochet-Bonnet esthesiometer at screening, post-procedure week 1-4 (visit 4-Visit 7), and week 8 (visit 8).
Timepoint [1] 412056 0
Data will be collected regarding this timepoint at Screening visit, post-procedure week 1-4 (visit 4-Visit 7), and week 8 (visit 8) to evaluate this outcome.
Secondary outcome [2] 412057 0
2) Visual acuity: Change in Best Corrected Visual Acuity (BCVA) will be assessed from Screening visit and visits post-procedure day 1 visit through week 8 visits (Visits 3 through 8). The VA will be measured using a LogMAR chart at a standard photopic light level of at least 85 cd/m1. If a LogMAR cart is unavailable, a Snellen chart may be used.
Timepoint [2] 412057 0
Data will be collected regarding this timepoint at Screening visit, post-procedure day 1 (V3), post-procedure week 1-4 (visit 4-Visit 7), and week 8 (visit 8) to evaluate this outcome.
Secondary outcome [3] 412058 0
3) Ocular Discomfort: A composite of the below test/assessments will be utilized to support this secondary outcome. Change in the 7-point Visual Analog Scale (VAS)- Symptom Index, and the 4-point Standard Patient Evaluation of Eye Dryness (SPEED) Questionnaire will be evaluated. Subjects will complete the VAS Symptom Index and SPEED Questionnaires at Screening Visit (V1), Post-procedure Week 1 (V4), Post-procedure Week 2 (V5), Post-procedure Week 3 (V6), Post-procedure Week 4 (V7), and Post-procedure Week 8 (V8).
Timepoint [3] 412058 0
Data will be collected regarding this timepoint at Screening visit (V1), post-procedure week 1-4 (visit 4-Visit 7), and week 8 (visit 8) to evaluate this outcom
Secondary outcome [4] 412061 0
4) Discomfort During Treatment: Patient discomfort associated with the treatment will be evaluated a visual analog scale questionnaire using a scale of 0-100 indicating the discomfort in or around their eyelids, or face during the procedure. Assessments will be made immediately post-treatment (V2) and post-procedure day 1 (V3).
Timepoint [4] 412061 0
Data will be collected regarding this outcome are immediately post-treatment (V2) and post-procedure day 1 (V3).

Eligibility
Key inclusion criteria
1) adult patients age 21 or older of any gender
2) At least moderate ocular surface discomfort (dryness, discomfort, grittiness, itchiness, burning, stabbing, shooting, or aching pain) that significantly improves with application of topical anesthetic in the to-be-treated eye, as per investigator assessment
3) Normal lid anatomy, blink, and closure as determined by the investigator
4) If a contact lens user, willingness to stay out of contact lenses in the treated eye for 24 hours pre- and post-procedure
5) Willingness to participate in the study as evidenced by signing of an informed consent document
Minimum age
21 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Pregnancy, breastfeeding, or planning to become pregnant or breastfeeding
2) Known allergy or hypersensitivity to copper, gold or aluminum.
3) Corneal Punctate Epithelial Erosions worse than 2+ in the to be treated eye as determined by Lissamine green or fluorescein staining using the Oxford Grading Scale
4) A history of corneal transplant (penetrating keratoplasty or endothelial keratoplasty), other significant corneal endothelial disease, or a history of keratoconus, corneal thinning, or other corneal ectasias
5) Any active ocular infection (bacterial, viral, or fungal), or active ocular inflammation, or any prior history of uveitis, at the time of the Screening Visit
6) A history of herpes keratitis, non-healing corneal epithelial defects, or neurotrophic keratopathy due to stem cell deficiency, diabetic keratopathy, lagophthalmos, topical anesthetic abuse, or any other cause
7) At Screening Visit, intraocular pressure (IOP) may not be less than 5 mmHg or be greater than 25 mmHg
8) Any history of significant prior conjunctival surgery (such as pterygium, trabeculectomy or scleral buckle surgery)
9) Planned eye surgery during the study period
10) Participation in any clinical study of an investigational product within 30 days prior to enrollment
11) Any change in dose in the last 30 days to a centrally acting neuromodulator (such as gabapentin, pregabalin, serotonin and norepinephrine reuptake inhibitors (SNRIs)), cannabinoid use, or to an ophthalmic anti-inflammatory drug (such topical cyclosporine (Restasis), lifitegrast (Xiidra), autologous serum tears, topical/oral steroids, or topical/oral non-steroidal anti-inflammatory drugs)
12) Any history of serious, poorly controlled systemic or ophthalmic condition or circumstances which, in the opinion of the Investigator, could compromise the subject’s ability to comply with the protocol or that could compromise the subject’s safety or the interpretation of the clinical trial results.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
not applicable
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
In this study, four cohorts consisting of four subjects each will be treated in one eye with the ETX-4143 2.0 Device with progressively longer durations of exposure. This method will be used to determine the optimal duration of treatment. After enrollment of Cohort A and prior to enrollment of Cohort B, the Data Safety Monitor (DSM) will review the 1-week safety data of the 4 subjects enrolled in Cohort A. Subsequently, the DSM will again review the 1-week safety data for Cohort B prior to expanding to Cohort C, and for Cohort C prior to expanding to Cohort D. Following each review, the DSM will provide recommendation regarding enrollment of the remaining subjects.
All subjects will be followed for a total of 8 weeks. Subjects will have only the worse eye treated.
Phase
Not Applicable
Type of endpoint/s
Safety
Statistical methods / analysis
Prior to database lock, the Sponsor will finalize a Statistical Analysis Plan (SAP) detailing all planned analyses. Any analyses conducted in addition to those specified in the SAP will be clearly documented as post hoc.
Quantitative variables will be summarized descriptively using number of subjects (n), mean, standard deviation, median, minimum, and maximum. Qualitative variables will be summarized using counts and percentages.
Summaries will be provided for demographics, baseline medical history, concurrent therapies, and subject disposition.
All analyses will be two-sided at a significance level of 0.05. The 95% confidence intervals will be provided where appropriate.
The SAP will serve as the final determinant of the statistical procedures, notwithstanding anything herein.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
16/08/2023
Actual
28/08/2023
Date of last participant enrolment
Anticipated
15/12/2023
Actual
Date of last data collection
Anticipated
15/02/2024
Actual
Sample size
Target
16
Accrual to date
2
Final
Recruitment in Australia
Recruitment state(s)
NSW,WA,VIC
Recruitment hospital [1] 22859 0
Centre for Eye Research Australia - East Melbourne
Recruitment hospital [2] 22860 0
Minas Coroneo, AO (Private Clinic) - Randwick
Recruitment hospital [3] 25602 0
Lions Eye Institute Day Surgery Centre - Nedlands
Recruitment postcode(s) [1] 38158 0
2031 - Randwick
Recruitment postcode(s) [2] 38157 0
3002 - East Melbourne
Recruitment postcode(s) [3] 41427 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 311890 0
Commercial sector/Industry
Name [1] 311890 0
EyeCool Therapeutics, Inc.
Country [1] 311890 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
EyeCool Therapeutics, Inc
Address
One Mifflin Place, Suite 320
Cambridge, Massachusetts 02138 U.S.A.
Country
United States of America
Secondary sponsor category [1] 313370 0
Commercial sector/Industry
Name [1] 313370 0
EyeCool Therapeutics Pty Ltd
Address [1] 313370 0
Studio 4, 9 Mogo Place
Billinudgel NSW 2483 AUS
Country [1] 313370 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311324 0
St. Vincents Hospital Melbourne HREC
Ethics committee address [1] 311324 0
41 Victoria Parade, Fitzroy VIC 3065
Ethics committee country [1] 311324 0
Australia
Date submitted for ethics approval [1] 311324 0
02/08/2022
Approval date [1] 311324 0
30/06/2023
Ethics approval number [1] 311324 0
Ethics committee name [2] 311326 0
Bellberry Limited
Ethics committee address [2] 311326 0
123 Glen Osmond Road, Eastwood, South Australia 5063
Ethics committee country [2] 311326 0
Australia
Date submitted for ethics approval [2] 311326 0
10/08/2022
Approval date [2] 311326 0
Ethics approval number [2] 311326 0

Summary
Brief summary
The purpose of this research study is to provide safety information for a new eye pain management option for patients that have been diagnosed with moderate to severe eye pain. Ocular (Eye) surface disease is a debilitating problem causing chronic pain for many patients and is often due to more than one cause. In many of these patients, even with treatment of the underlying cause, the patient is left with persistent, symptomatic eye surface pain. Recent research has identified a link between patients with chronic ocular surface discomfort, and the sensory receptors for painful stimulus, Topical cooling has a long, well-established association with temporarily reducing peripheral peripheral nerve sensitivity. Recently, in other clinical uses of applied topical cooling, it was noted that some patients had a reduced sensitivity.

The ETX-4143 device delivers a cooling treatment that is applied to the surface of the eye via a handheld medical device that contains an internal frozen (-20° Centigrade) mixture of purified water and glycerol; ETX-4143 2.0 Device does not contain an active pharmaceutical ingredient. It is applied topically to the scleral surface and the temperature is transferred via a metal plate. Depending on when you are enrolled into the study, the cooling treatment will be applied for either 30 seconds, 2 minutes, 6 minutes, or 10 minutes.

Approximately 16 subjects will be enrolled at three clinical sites in Australia. There will be a total of 8 subject visits occurring over 8 weeks. Each visit should take approximately 2 hours.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 120718 0
Prof Mark Davies Daniell
Address 120718 0
Centre for Eye Research Australia
Level 7, 32 Gisborne Street
East Melbourne VIC 3002
Country 120718 0
Australia
Phone 120718 0
+61 3 9417 1079
Fax 120718 0
+61 3 9416 1435
Email 120718 0
daniellm@unimelb.edu.au
Contact person for public queries
Name 120719 0
Dr James A Stefater, MD, PhD
Address 120719 0
EyeCool Therapeutics, Inc.
One Mifflin Place, Suite 320
Cambridge, Massachusetts 02138 U.S.A.
Country 120719 0
United States of America
Phone 120719 0
+61 1800 9340 66
Fax 120719 0
Email 120719 0
clinical@eyecooltx.com
Contact person for scientific queries
Name 120720 0
Dr James A Stefater, MD, PhD
Address 120720 0
EyeCool Therapeutics, Inc.
One Mifflin Place, Suite 320
Cambridge, Massachusetts 02138 U.S.A.
Country 120720 0
United States of America
Phone 120720 0
+61 1800 9340 66
Fax 120720 0
Email 120720 0
clinical@eyecooltx.com

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


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.