A Study to Evaluate the Safety and Tolerability of EXN407

A Randomised, Double-Masked Vehicle-Controlled, Multiple Dose, Dose Escalation Study To Evaluate The Safety and Tolerability of EXN407 in Subjects With Centre Involved Diabetic Macular Oedema Secondary to Diabetes Mellitus

This first in human (FIH), Phase Ib/II study of EXN407 is a randomised, double-masked, vehicle-controlled, multiple dose, dose-escalating study to evaluate the safety and tolerability of EXN407 in subjects with centre involved Diabetic Macular Oedema (DMO), with Centre-subfield macular thickness (CMT) between 280-420 µm and Best corrected visual acuity (BCVA) better than or equal to 69 ETDRS score (approximate Snellen equivalent 20/40 (6/12 letters) in the study eye, which is considered secondary to diabetes mellitus.

This study will provide a basis for further clinical development of EXN407 ophthalmic solution.

Study Overview

• Status: Completed
• Conditions: Diabetic Macular Edema
• Intervention / Treatment: Drug: EXN407

Detailed Description

EXN407 or vehicle-control solution administered unilaterally to the study eye only. To select the study eye the Investigator examines the subjects and identifies which eye exhibits centre involved DMO with a CMT between 280-420 μm (as determined by SD-OCT). Further, all other inclusion/exclusion criteria required to be met.

Dose Escalation Cohorts The study assesses the safety and tolerability of EXN407 in eligible subjects with center involved Diabetic Macular Oedema (DMO) at up to 3 escalating dose (concentration) levels and placebo (vehicle) consisting of an excipient formulation adjusted for osmolality. EXN407 or vehicle-control administered as a single 30 μL drop by unilateral eye drop administration to the study eye only, and the drops dosed BID for 7 days. Subjects assessed throughout the treatment period for safety, tolerability, and efficacy at Follow-up visits. Each of the ascending dose subject cohorts consists of 4 subjects (3 subjects randomised to receive EXN407 and 1 subject randomised to receive placebo).

Dose Expansion Cohort The highest well tolerated dose of EXN407 (as recommended by the DEC) is evaluated in a subject expansion cohort in eligible subjects with center involved Diabetic Macular Oedema (DMO) which consists of up to a maximum of 40 subjects (randomised to receive EXN407 at the selected dose or vehicle at a 2:1 drug: placebo ratio). Each eligible subject in the expansion cohort to receive study drug for up to 84 days, resulting in a total of 168 doses (168 single drops of 30 μL volume) of EXN407 or vehicle.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Sydney, Australia
    • Sydney Retina Clinic & Day Surgery
  • New South Wales
    • Macquarie, New South Wales, Australia, 2109
      • Macquarie University
    • Parramatta, New South Wales, Australia, 2150
      • Marsden Eye Specialists
    • Sydney, New South Wales, Australia, 2000
      • Sydney Eye Hospital/Save Sight Institution
    • Sydney, New South Wales, Australia, 2135
      • Strathfield Retina Clinic
    • Waratah, New South Wales, Australia, 2298
      • Newcastle Eye Hospital Foundation
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Adelaide Eye and Retina Centre
  • Victoria
    • Melbourne, Victoria, Australia, 3002
      • Centre for Eye Research Australia (CERA)
    • Melbourne, Victoria, Australia, 3146
      • Retinology Institute
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Lions Eye Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subject is at least 18 years of age inclusive, at the time of signing the informed consent.
2. BCVA better than or equal to 69 ETDRS score (approximate Snellen equivalent 20/40 or 6/12) in the study eye using the ETDRS visual acuity scale at Screening or BCVA less than 69 ETDRS score (approximate Snellen equivalent 20/50 or 6/15) but who, in the Investigator's opinion, is unsuitable for treatment with anti-VEGF by intravitreal injection or refuses it. Subjects should have no more than a 7-letter difference in BCVA at Screening and baseline visit.
3. Ocular media is consistent with SD-OCT imaging and cataracts are not expected in the subject for the duration of the study.
4. The subject has no other retinal disease.
5. Subject or the subject's partner successfully demonstrates their ability to self-administer/administer eye drops at Screening, with multiple attempts allowed at the discretion of the Investigator.

Exclusion Criteria:

1. Any other retinal disease in the study eye, other than centre involved DMO or diabetic retinopathy.
2. Poor vision (VA 6/60 or worse) in the contralateral eye.
3. Intraocular inflammation (including trace or greater) in the study eye. History of idiopathic or autoimmune uveitis in either eye.
4. Use of intravitreal anti-VEGF drugs including ranibizumab, bevacizumab, aflibercept in the study eye within 6 months of the Screening Visit, or in the fellow (non study) eye within 3 months of the Screening Visit. Use of topical corticosteroids or topical non-steroidal anti-inflammatory agents in the study eye within 28 days of the Screening Visit. Use of intravitreal corticosteroids in either eye or systemic steroids within 12 months of the Screening Visit. Prior use of Iluvien (without time limitation).
5. Within 180 days prior to the Screening visit, use of medications known to be toxic to the retina, lens or optic nerve (e.g. desferoximine, chloroquine/hydrochloroquine, chlorpromazine, phenothiazines, tamoxifen, and ethambutol).
6. History of (within 90 days of Screening date) cerebral vascular accident (stroke) or MI.
7. Significant renal impairment including subjects on chronic renal dialysis and subjects with a history of nephrectomy or kidney transplant (regardless of renal function).
8. History of anaphylaxis, anaphylactoid (resembling anaphylaxis) reactions, or severe allergic responses.
9. Positive pregnancy test (all female subjects of childbearing potential must have a urine β-human chorionic gonadotropin [hCG] pregnancy test performed at Screening and within 7 days prior to randomisation) or is known to be pregnant or lactating.
10. Known to have, or history of a positive test result for, hepatitis B or C, HIV, syphilis, tuberculosis, or COVID-19.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation Cohort 1; Each subject will receive a low-dose 0.5 mg/mL (0.05%) of EXN407 or placebo twice a day in 14 doses over a 7 day period.	Drug: EXN407; EXN407 or placebo will be administered as a single 30 microliters drop twice a day, by unilateral eye drop administration to the study eye only.
Experimental: Dose Escalation Cohort 2; Each subject will receive a mid-dose 1 mg/mL (0.1%) of EXN407 or placebo twice a day in 14 doses over a 7 day period.	Drug: EXN407; EXN407 or placebo will be administered as a single 30 microliters drop twice a day, by unilateral eye drop administration to the study eye only.
Experimental: Dose Escalation Cohort 3; Each subject will receive a high-dose 1.5 mg/mL (0.15%) of EXN407 or placebo twice a day in 14 doses over a 7 day period.	Drug: EXN407; EXN407 or placebo will be administered as a single 30 microliters drop twice a day, by unilateral eye drop administration to the study eye only.
Experimental: Dose Expansion Cohort; The highest well-tolerated dose of EXN407 will be evaluated where subjects will receive EXN407 at the selected dose or placebo twice a day for up to 84 days resulting in a total of 168 doses	Drug: EXN407; EXN407 or placebo will be administered as a single 30 microliters drop twice a day, by unilateral eye drop administration to the study eye only.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Primary Objective of the Study is to Evaluate the Ocular Safety and Tolerability (by Incidence of Ocular Adverse Events) of EXN407 Ophthalmic Solution in Dose Escalation Phase.	Number of Participants with Ocular Treatment Emergent Adverse Events (TEAEs)	Assessed starting from Day 1 of treatment to Day 36 in Dose Escalation.
The Primary Objective of the Study is to Evaluate the Ocular Safety and Tolerability (by Incidence of Ocular Adverse Events) of EXN407 Ophthalmic Solution in Dose Expansion Phase.	Number of Participants with Ocular Treatment Emergent Adverse Events (TEAEs)	Assessed starting from Day 1 of treatment to Day 113 in Dose Expansion phase.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To Evaluate the Systemic Pharmacokinetics of EXN407 Ophthalmic Solution in Subjects With DMO Secondary to Diabetes Mellitus by Tmax.	Measured by characterizing the PK profile by estimating the time of the maximum plasma drug concentration (Tmax) of EXN407 in plasma.	Blood draws for PK will be collected only on Day 3(Dose Escalation) and Day 8(Dose Expansion) at the following timepoints: pre-dose and 15 mins, 30 mins, 1, 2, 3,and 4 hours post-dose.
To Evaluate the Systemic Pharmacokinetics of EXN407 Ophthalmic Solution in Subjects With DMO Secondary to Diabetes Mellitus by Cmax	Measured by characterizing the PK profile by estimating the maximum observed drug plasma concentration (Cmax) of EXN407 in plasma.	Blood draws for PK will be collected only on Day 3(Dose Escalation) and Day 8(Dose Expansion) at the following timepoints: pre-dose and 15 mins, 30 mins, 1, 2, 3,and 4 hours post-dose.
To Evaluate the Systemic Pharmacokinetics of EXN407 Ophthalmic Solution in Subjects With DMO Secondary to Diabetes Mellitus by AUC.	Measured by characterizing the PK profile by estimating the area under the curve (AUC) of EXN407 in plasma.	Blood draws for PK will be collected only on Day 3(Dose Escalation) and Day 8(Dose Expansion) at the following timepoints: pre-dose and 15 mins, 30 mins, 1, 2, 3,and 4 hours post-dose.
To Evaluate the Systemic Pharmacokinetics of EXN407 Ophthalmic Solution in Subjects With DMO Secondary to Diabetes Mellitus by t½.	Measured by characterizing the PK profile by estimating the apparent elimination half-life (t½) of EXN407 in plasma.	Blood draws for PK will be collected only on Day 3(Dose Escalation) and Day 8(Dose Expansion) at the following timepoints: pre-dose and 15 mins, 30 mins, 1, 2, 3,and 4 hours post-dose.
To Evaluate Changes in Ocular Functional Measures as Assessed Using Ophthalmoscopy.	Measured by the changes from baseline in ophthalmic examination finding through ophthalmoscopy (BCVA (Letters))	From Day 1 of Treatment to End of Treatment i.e. assessed upto 36 Days/EOS in Dose Escalation and upto 4 months(113 days/EOS) in Dose Expansion.
To Evaluate Changes in Ocular Structural Measures as Assessed Using Ophthalmoscopy.	Measured by the changes from baseline in ophthalmic examination finding through ophthalmoscopy (corneal thickness).	From Day 1 of Treatment to End of Treatment i.e. assessed upto 36 Days/EOS in Dose Escalation and up to 4 months(113 days) in Dose Expansion.

Collaborators and Investigators

• Sponsor: Exonate Limited
• Collaborators: Novotech (Australia) Pty Limited
• Investigators: Principal Investigator: Mark Gillies, Prof, Sydney Eye Hospital/Save Sight Institution; Principal Investigator: Andrew Chang, A/Prof, Sydney Retina Clinic & Day Surgery; Principal Investigator: Sanjeewa Wickremasinghe,, Prof, Centre for Eye Research Australia (CERA); Principal Investigator: Fred Chen, Dr, Lions Eye Institute; Principal Investigator: Jolly Gilhotra, A/Prof, Adelaide Eye and Retina Centre; Principal Investigator: Wilson Heriot, A/Prof, ZAVe Clinical Research Management - Retinology Institute; Principal Investigator: Hemal Mehta, Dr, Strathfield Retina Clinic; Principal Investigator: Peter Davies, Dr, Newcastle Eye Hospital Foundation; Principal Investigator: Rohan Merani, Dr, Macquarie University; Principal Investigator: Helene Cass, Dr, Marsden Eye Specialists; Principal Investigator: Lily Ooi, Princess Alexandra Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2020
• Primary Completion (Actual): October 25, 2022
• Study Completion (Actual): November 29, 2022

Study Registration Dates

• First Submitted: August 26, 2020
• First Submitted That Met QC Criteria: September 24, 2020
• First Posted (Actual): September 25, 2020

Study Record Updates

• Last Update Posted (Actual): May 9, 2025
• Last Update Submitted That Met QC Criteria: April 23, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Diseases; Retinal Degeneration; Macular Degeneration; Macular Edema
• Other Study ID Numbers: PQ-110-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No