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Trial registered on ANZCTR


Registration number
ACTRN12624000997550
Ethics application status
Approved
Date submitted
29/07/2024
Date registered
14/08/2024
Date last updated
15/09/2024
Date data sharing statement initially provided
14/08/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase II, Multicentre, 2-part, Study of the Safety, Tolerability, and Efficacy of Intravitreal Fludrocortisone Acetate in Subjects with Geographic Atrophy Secondary to Age-related Macular Degeneration - Part B
Scientific title
A Phase II, Multicentre, 2-part, Study of the Safety, Tolerability, and Efficacy of Intravitreal Fludrocortisone Acetate in Subjects with Geographic Atrophy Secondary to Age-related Macular Degeneration - Part B
Secondary ID [1] 312580 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record
ACTRN12624000971538 is Part A of this study

Health condition
Health condition(s) or problem(s) studied:
Geographic atrophy (GA) secondary to age-related macular degeneration (AMD) 334507 0
Condition category
Condition code
Eye 331123 331123 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Part B:
A randomised, double masked, sham controlled evaluation of the safety and efficacy of intravitreal fludrocortisone acetate (FCA) in subjects with GA secondary to AMD in 126 subjects over 52 weeks. Following screening, the schedule of activities includes attendance on Day 1, then Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and Week 52 or end of study for efficacy and safety assessments.

Each visit will take between 1 and 2 hours. Assessments vary depending upon the visit schedule and will include; evaluation of nature, frequency, and severity of adverse events (AEs)/ serious adverse events (SAEs), including relationship to study intervention, AEs leading to study intervention discontinuation or study discontinuation, assessments of adverse event of special interest (AESI), which includes endophthalmitis, retinal detachment, traumatic cataract, and increased intraocular pressure (IOP), ophthalmic examinations (slit lamp biomicroscopy, dilated ophthalmoscopy) and imaging assessment (spectral domain optical coherence tomography [SD-OCT], colour fundus photography [CFP], fundus fluorescein angiography [FFA]), changes in haematology and clinical chemistry laboratory parameters, routine urinalysis, vital signs (blood pressure, pulse rate, and temperature), and physical examination.

Dosing: Participants will receive either a dose of FCA 2 mg/0.1 mL or sham to one eye (study eye) administered on day 1, week 12, week 24 and week 36 (4 doses in total) by an ophthalmologist.

Only one eye will be selected as the study eye. If both eyes are eligible, the eye with worse VA and/or visual function will be chosen as the study eye. If both eyes have the same visual function, the eye with the larger GA area will be considered as the study eye.

Intervention adherence will be documented on investigational product (IP) dispensing and administration logs. Study participation time is up to 56 weeks from screening to end of study.
Intervention code [1] 329101 0
Treatment: Drugs
Comparator / control treatment
Part B: Sham control group

Sham control group will use an empty vial and a sham injection.
Sham control injections were chosen to minimise the known risk of IVT injection-related adverse events (e.g., endophthalmitis).
Control group
Placebo

Outcomes
Primary outcome [1] 338877 0
Part B: To evaluate the efficacy of FCA IVT injections in subjects with early GA secondary to AMD
Timepoint [1] 338877 0
Day 1 (injection day) and weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 post first injection or early discontinuation (ED).
- FAF & IR
Secondary outcome [1] 437773 0
Part B: To evaluate the efficacy of FCA IVT injections on visual acuity in subjects with early GA secondary to AMD
Timepoint [1] 437773 0
Day 1 (injection day) and weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 post first injection or ED or as required
- BCVA and
- LL-BCVA
Secondary outcome [2] 437774 0
Part B: To evaluate the efficacy of FCA IVT injections on visual function in subjects with early GA secondary to AMD
Timepoint [2] 437774 0
Day 1 (injection day) and weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 post first injection or ED or as required
- BCVA and
- LL-BCVA
Secondary outcome [3] 437775 0
Part B: To evaluate the safety and tolerability of FCA IVT injections in subjects with early GA secondary to AMD
Timepoint [3] 437775 0
Day 1 (injection day) and weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 post first injection or ED or as required
-AEs, full and abbreviated (as required based on symptoms) physical examination, vital signs, IOP, ophthalmic examinations, and ophthalmic imaging.

Screening, then Day 1 (injection day) and weeks 12, 24, 36, 52 post first injection, or ED, or as required
-Urine pregnancy test

Screening, then Day 1 (injection day) and weeks 12, 24 and 36 post first injection or as required
- CFP plus anterior segment

Screening then Weeks 12, 24, 36 and 48 post first injection or as required
- Urinanalysis

Screening, then Week 12, 24, 36, and 52 post first injection, or ED, or as required
- Haematology and clinical chemistry

Screening then Week 52 post first injection or ED
- FFA
Secondary outcome [4] 437819 0
Part B: To evaluate the effect of FCA IVT injections on vision-related quality of life (QoL) in subjects with early GA secondary to AMD
Timepoint [4] 437819 0
Day 1 (injection day) and weeks 24 and 52 post first injection or ED
-NEI VFQ-25 score

Eligibility
Key inclusion criteria
1. The subject must voluntarily sign and date an informed consent, approved by the HREC, prior to the initiation of any screening or study-specific procedures. A legally authorised representative may be used in case the subject is unable to read due to literacy.
2. In the opinion of the Investigator, willing and able to follow study instructions and likely to complete all scheduled study visits.
3. Male or female subjects.
4. Subjects aged 50 years and over.
5. Female subjects must be of nonchildbearing potential or show a negative pregnancy test at screening and must agree to use appropriate methods of contraception during the study.
6. Males with female partners of childbearing potential must agree to use appropriate methods of contraception and agree to refrain from donating sperm during the study.
7. BCVA of 30 letters or better using Early Treatment Diabetic Retinopathy Study (ETDRS) charts (20/200 Snellen equivalent).
8. Diagnosis of GA secondary to AMD, confirmed using FAF within 28 days prior to randomisation, to the following criteria:
a. GA defined as a sharply delineated, roughly round or oval area of partial or complete retinal pigment epithelium (RPE) depigmentation, resulting in better visibility of the underlying large choroidal vessels
b. Total GA area must be greater than or equal to 1.25mm2 and less than or equal to 17.5 mm2
- If GA is multifocal, at least one focal lesion must be greater than or equal to 1.25mm2
c. The GA lesion/s must be completely visualised on the macula centred image, able to be imaged in its entirety, and must be able to be measured separately from any areas of peripapillary atrophy
d. Presence of any pattern of hyper-autofluorescence in the junctional zone of GA.
9. Sufficiently clear ocular media, adequate pupillary dilation, fixation to permit quality fundus imaging, and ability to cooperate for adequate visual function testing and anatomic assessment in the study eye.
Minimum age
50 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. GA due to causes other than AMD such as Stargardt disease, cone rod dystrophy, or toxic maculopathies like plaquenil maculopathy.
2. Spherical equivalent refractive error of -6.00 diopters of myopia or worse, or an axial length greater than 26 mm.
3. Any history, or current evidence of exudative (“wet”) AMD; including any evidence of RPE rips or evidence of neovascularisation anywhere in the retina.
4. Retinal disease other than AMD; however, benign conditions of the vitreous or peripheral retina are not exclusionary (ie, pavingstone degeneration).
5. Any ophthalmologic condition that reduces the clarity of the media and that, in the opinion of the Investigator, interferes with ophthalmologic examination and/or prevents adequate imaging of the retina (e.g. advanced cataract or corneal abnormalities).
6. Intraocular surgery (including lens replacement surgery) within 3 months prior to randomisation.
7. Aphakia or absence of the posterior capsule
- Previous violation of the posterior capsule is also excluded unless it occurred as a result of yttrium aluminium garnet (YAG) laser posterior capsulotomy in association with prior posterior chamber intraocular lens implantation and at least 60 days prior to Day 1.
8. Any ophthalmic condition that may require surgery during the study period.
9. Any contraindication to IVT injection including current ocular or periocular infection in either eye.
10. History of uveitis or endophthalmitis in either eye.
11. Current uncontrolled intraocular pressure (determined by the Investigator) or history of ocular hypertension or glaucoma.
12. Presence of iris neovascularisation and/or vitreous or preretinal haemorrhage.
13. Prior vitrectomy, glaucoma filtration surgery, or any ocular procedure which could affect drug distribution or clearance.
14. Ocular trauma to the eye within the preceding 6 months.
15. Participation in another interventional clinical study, or use of any experimental treatment for AMD or any other investigational product within 6 weeks or 5 half-lives (whichever is longer) prior to the start of study treatment. Clinical trials solely involving observation, over-the-counter vitamins, supplements, or diets are not exclusionary.
16. Systemic conditions which may contraindicate the use of mineralocorticoids, e.g. tuberculosis, uncontrolled hypertension, hypothyroidism, Cushing’s syndrome, hypokalaemia, myasthenia gravis, fungal infections, chronic heart failure, kidney disease with reduction in kidney function and fluid retention in the legs, or feet, or arms, or hands.
17. Medical or psychiatric conditions that, in the opinion of the Investigator, make consistent follow-up over the study period unlikely, or in general a poor medical risk because of other systemic diseases or active uncontrolled infections.
18. Screening laboratory value (haematology, serum chemistry, or urinalysis) that in the opinion of the Investigator is clinically significant and not suitable for study participation.
19. Hypersensitivity to fluorescein

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 computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation using a randomisation table from a statistics book
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving 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
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
23/09/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
126
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 317012 0
Commercial sector/Industry
Name [1] 317012 0
EyeCo Pty Ltd
Country [1] 317012 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
EyeCo Pty Ltd
Address
Country
Australia
Secondary sponsor category [1] 319256 0
None
Name [1] 319256 0
Address [1] 319256 0
Country [1] 319256 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 315768 0
Bellberry Human Research Ethics Committee A
Ethics committee address [1] 315768 0
123 Glen Osmond Road, Eastwood, Adelaide South Australia
Ethics committee country [1] 315768 0
Australia
Date submitted for ethics approval [1] 315768 0
16/07/2024
Approval date [1] 315768 0
02/09/2024
Ethics approval number [1] 315768 0
2024-07-896

Summary
Brief summary
The study has two parts: A and B. This information is for part B.

Part B of the study will test the safety and efficacy of giving 4 doses of fludrocortisone (study drug) to people with geographic atrophy (GA), which is an advanced form of age-related macular degeneration (AMD).
Age-related macular degeneration (AMD) is a disease of the macula, an area in the retina found at the back of the eye, needed for sharp, clear vision and activities such as reading and sewing. The advanced form of dry AMD is known as geographic atrophy (GA) (a region of the retina where the cells wither away and die). Sometimes, these regions of GA look like a map to the doctor who is examining the retina, hence the term “geographic atrophy.” The purpose of this study is whether fludrocortisone (study drug) is safe to give to people with GA and if it can prevent or slow down the progression of GA.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 135730 0
Dr Thomas Pham
Address 135730 0
Sydney Retina Clinic and Day Surgery, Level 13, Park House, 187 Macquarie Street, Sydney, NSW 2000
Country 135730 0
Australia
Phone 135730 0
+61 2 80225838
Fax 135730 0
Email 135730 0
[email protected]
Contact person for public queries
Name 135731 0
Dr Thomas Hong
Address 135731 0
GreenLight Clinical, 134 William Street, Woolloomooloo NSW 2011
Country 135731 0
Australia
Phone 135731 0
+61 2 9191 0640
Fax 135731 0
Email 135731 0
[email protected]
Contact person for scientific queries
Name 135732 0
Dr Thomas Hong
Address 135732 0
GreenLight Clinical, 134 William Street, Woolloomooloo NSW 2011
Country 135732 0
Australia
Phone 135732 0
+61 2 9191 0640
Fax 135732 0
Email 135732 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
Deidentified overall patient data will be available or shared. Currently it is not planned to submit IPD, however should this change, this record will be updated


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.