A Study to Evaluate the Safety and Tolerability of EXN407

April 23, 2025 updated by: Exonate Limited

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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
48

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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.
Time Frame: Assessed starting from Day 1 of treatment to Day 36 in Dose Escalation.
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.
Time Frame: Assessed starting from Day 1 of treatment to Day 113 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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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.
Time Frame: 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.
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
Time Frame: 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.
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.
Time Frame: 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.
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.
Time Frame: 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.
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.
Time Frame: 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.
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.
Time Frame: 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.
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

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Exonate Limited

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Novotech (Australia) Pty Limited

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 5, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 25, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 29, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 26, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 24, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 25, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 9, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 23, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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