Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001718831
Ethics application status
Approved
Date submitted
16/11/2021
Date registered
16/12/2021
Date last updated
2/03/2022
Date data sharing statement initially provided
16/12/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Phase I study of a Latanoprost Ocular Implant for treatment of Open Angle Glaucoma or Ocular Hypertension.
Scientific title
Open label study to evaluate the safety, tolerability and biodegradation period of PA5346 Latanoprost Free Acid (FA) Sustained Release (SR) Ocular Implant when administered to patients with Open Angle Glaucoma or Ocular Hypertension.
Secondary ID [1] 305721 0
LATA-CS103
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Open Angle Glaucoma 324190 0
Ocular Hypertension 324191 0
Condition category
Condition code
Eye 321675 321675 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
PA5346 ocular implant is a small, clear rod-shaped implant that is placed in the anterior (front) chamber of the eye, at a single timepoint, and slowly releases a drug called latanoprost free acid (100ng/day) over a period of approximately 30 weeks. The implant has been designed to slowly disappear (naturally breakdown and be reabsorbed back into the body), so there is no need for it to be removed. If the implant is proven to work effectively, it could significantly improve the treatment of glaucoma by substituting for eye drops to control the pressure in the eye, and ensure the patient always receives the daily dose of latanoprost free acid that they need.

All administrations of the ocular implant will be undertaken by a qualified and trained ophthalmologist.
Intervention code [1] 322112 0
Treatment: Drugs
Intervention code [2] 322113 0
Treatment: Devices
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 329446 0
To assess the safety and tolerability of 100 ng/day PA5346 Latanoprost FA SR Ocular Implant in adults with open angle glaucoma (OAG) or ocular hypertension (OHT).

Safety and tolerability will be assessed by:
- patient reported side effects
- blood and urine tests
- Physical exams and vital signs
- Eye tests
Timepoint [1] 329446 0
Patients are assessed until the ocular implant has completely biodegraded and the intraocular pressure in their study eye has returned to its normal clinical care range. It is anticipated that the implant will completely degrade no sooner than 20 weeks and no later than 12 months after the date of administration.

Safety assessments will occur as follows:
- blood and urine tests - Weeks 12 and 12 weeks after the implant has disappeared.
- Physical exams and vital signs - Weeks 12, 30, 40, 42 and each subsequent 6 weeks thereafter until the implant has degraded and 12 weeks after the implant has disappeared.
- Eye tests - Weeks 6, 12, 18, 26, 30, 34, 40, 42 and each subsequent 6 weeks thereafter until the implant has degraded and 12 weeks after the implant has disappeared.
Primary outcome [2] 329447 0
To assess the period of biodegradation of 100 ng/day PA5346 Latanoprost FA SR Ocular Implant in adults with OAG or OHT.

Biodegradation will be assessed by Gonioscopy or anterior Optical Coherence Tomography (OCT). These tests allow the implant to be located by the ophthalmologist.
Timepoint [2] 329447 0
Weeks 6, 12, 18, 26, 34, 40 and each subsequent 6 week visit thereafter until the implant has completely degraded
Secondary outcome [1] 402646 0
To assess the initial efficacy of 100 ng/day PA5346 Latanoprost FA SR Ocular Implant in controlling IOP during a study period in adults with OAG or OHT.

IOP will be assess by using a tonometer.
Timepoint [1] 402646 0
Day 1, and Weeks, 6, 18, 26, 34, 40 and thereafter at every 6 weekly visit after intervention commencement
Secondary outcome [2] 402647 0
Extent of hyperaemia. Assessed by Slit lamp Biomicroscopy and Efron grading scale for Conjunctival Redness
Timepoint [2] 402647 0
Baseline, Day 1, and Weeks, 6, 18, 26, 34, 40 and thereafter at every 6 weekly visit after intervention commencement
Secondary outcome [3] 402648 0
Ophthalmologist-reported ease of use of bespoke administration device

This questionnaire is descriptive only and includes questions such as:
• Ease of attaching the implant-containing needle to the administration device;
• Ease of inserting the implant in the correct location;
• Number of times the plunger is depressed to extrude the implant.
Timepoint [3] 402648 0
Day of Implantation

Eligibility
Key inclusion criteria
- Have given written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects.
- Diagnosis of OAG or OHT. Iridocorneal angle must be classified as Grade 3 or 4 on the modified Shaffer-Etienne scale by gonioscopy.
- Unmedicated (post-washout) 8:00 AM IOP of 24 mmHg to 36 mmHg in the ITT eye at either of two qualification visits 2 weeks apart. In addition, the IOP at 12:00 noon and 4:00 PM must be 20 mmHg to 36 mmHg on the same qualification visit where the 8:00 AM IOP was IOP 24 mmHg to 36 mmHg.
- Have a corrected visual acuity as determined by Early Treatment of Diabetic Retinopathy Study (ETDRS) charts in each eye greater than or equal to + 0.3 logMAR (equivalent to 6/12).
- Minimum central endothelial cell density of greater than or equal to 1600 cells/mm2 as determined by the reading centre adopted for the study.
- Currently managing their OAG or OHT with IOP lowering drop therapy, including a prostaglandin analogue.
- Are able and willing to follow study instructions and adhere to the protocol schedule and restrictions and undergo eye examinations
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Have pseudoexfoliation or pigment dispersion glaucoma
- Have aphakic eyes or only one functioning eye. only one eye.
- Have had iIntraocular surgery, glaucoma surgery or cornea/refractive surgery within the past 6 months or anticipate a need for eye surgery (including laser) in the study eye during the study period. .
- Significant corneal guttatae
- Ocular trauma in either eye within the three months prior to screening
- Current retinal detachment or history of blunt trauma in the study eye.
- Clinically significant ocular disease in either eye (e.g., corneal oedema, uveitis, severe keratoconjunctivitis sicca) which might interfere with the study Ocular trauma
- Have a known sensitivity to any component of the product (e.g. latanoprost, or polytriazole sensitivity), or to topical therapy used during the course of the study. Ocular infection or inflammation
- Have a clinical diagnosis of Fuchs’ Endothelial Corneal Dystrophy (FECD) in the study eye or have confluent central corneal guttatae, multiple central guttatae greater than a single cell, or corneal disease or abnormality that would prevent specular microscopy corneal scans of the study eye.
- Central corneal thickness in either eye that is less than 470 µm or greater than 630 µm at screening (or a difference between the eyes >70 µm).

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)
Allocation is not concealed
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
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
As this is an early Phase I safety study no formal sample size has been calculated. The planned number of participants is considered appropriate by the Sponsor to make initial determinations of the biodegradation time and clinical safety.

All safety assessments will be summarised using descriptive statistics and presented by timepoint.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
20/12/2021
Actual
Date of last participant enrolment
Anticipated
31/05/2022
Actual
Date of last data collection
Anticipated
31/03/2023
Actual
Sample size
Target
6
Accrual to date
0
Final
Recruitment outside Australia
Country [1] 24292 0
New Zealand
State/province [1] 24292 0
Wellington and Bay of Plenty

Funding & Sponsors
Funding source category [1] 310078 0
Commercial sector/Industry
Name [1] 310078 0
PolyActiva Pty Ltd
Country [1] 310078 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
PolyActiva Pty Ltd
Address
Level 9, 31 Queen St
Melbourne
VIC 3000
Australia
Country
Australia
Secondary sponsor category [1] 311137 0
None
Name [1] 311137 0
Address [1] 311137 0
Country [1] 311137 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309769 0
Southern Health and Disability Ethics Committee
Ethics committee address [1] 309769 0
Ministry of Health Health and Disability Ethics Committees
PO Box 5013.
Wellington 6140
Ethics committee country [1] 309769 0
New Zealand
Date submitted for ethics approval [1] 309769 0
28/10/2021
Approval date [1] 309769 0
26/01/2022
Ethics approval number [1] 309769 0
2021 FULL 11336

Summary
Brief summary
A multi centre, open label study to assess the safety and tolerability of PA5346 ocular implant in adults who have Open Angle Glaucoma or Ocular Hypertension. Participants who are currently administering Intraocular Pressure lowering drop therapy for Open Angle Glaucoma or Ocular Hypertension will be recruited. Drop therapy will cease in the treatment eye and continue in the contralateral eye. The treated eye will receive, via injection, a single PA5346 ocular implant. Participants will be monitored for safety and tolerability of the ocular implant until it completely biodegrades.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 115326 0
Prof Tony Wells
Address 115326 0
Capital Eye Specialists
Level 2/148 Cuba Street,
Te Aro,
Wellington 6011,
Country 115326 0
New Zealand
Phone 115326 0
+64 4 384 3937
Fax 115326 0
Email 115326 0
tw@eyetext.net
Contact person for public queries
Name 115327 0
Prof Tony Wells
Address 115327 0
Capital Eye Specialists
Level 2/148 Cuba Street,
Te Aro,
Wellington 6011,
Country 115327 0
New Zealand
Phone 115327 0
+64 4 384 3937
Fax 115327 0
Email 115327 0
tw@eyetext.net
Contact person for scientific queries
Name 115328 0
Dr Russell Tait
Address 115328 0
PolyActiva Pty Ltd
Level 9, 31 Queen St
Melbourne 3000 Victoria
Country 115328 0
Australia
Phone 115328 0
+61 3 9657 0700
Fax 115328 0
Email 115328 0
russell.tait@polyactiva.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Subject to internal decision making on how we wish to report the trial results.


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.