A Study to Evaluate the Safety and Tolerability of EXN407

NCT ID: NCT04565756

Last Updated: 2025-05-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-05
• Study Completion Date: 2022-11-29

Brief Summary

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.

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.

Conditions

Diabetic Macular Edema

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

EXN407

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

EXN407

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

EXN407

Intervention Type: DRUG

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.

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

Group Type: EXPERIMENTAL

EXN407

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novotech (Australia) Pty Limited

INDUSTRY

Sponsor Role: collaborator

Exonate Limited

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mark Gillies, Prof

Role: PRINCIPAL_INVESTIGATOR

Sydney Eye Hospital/Save Sight Institution

Andrew Chang, A/Prof

Role: PRINCIPAL_INVESTIGATOR

Sydney Retina Clinic & Day Surgery

Sanjeewa Wickremasinghe,, Prof

Role: PRINCIPAL_INVESTIGATOR

Centre for Eye Research Australia (CERA)

Fred Chen, Dr

Role: PRINCIPAL_INVESTIGATOR

Lions Eye Institute

Jolly Gilhotra, A/Prof

Role: PRINCIPAL_INVESTIGATOR

Adelaide Eye and Retina Centre

Wilson Heriot, A/Prof

Role: PRINCIPAL_INVESTIGATOR

ZAVe Clinical Research Management - Retinology Institute

Hemal Mehta, Dr

Role: PRINCIPAL_INVESTIGATOR

Strathfield Retina Clinic

Peter Davies, Dr

Role: PRINCIPAL_INVESTIGATOR

Newcastle Eye Hospital Foundation

Rohan Merani, Dr

Role: PRINCIPAL_INVESTIGATOR

Macquarie University

Helene Cass, Dr

Role: PRINCIPAL_INVESTIGATOR

Marsden Eye Specialists

Lily Ooi

Role: PRINCIPAL_INVESTIGATOR

Princess Alexandra Hospital

Locations

Macquarie University

Macquarie, New South Wales, Australia

Marsden Eye Specialists

Parramatta, New South Wales, Australia

Sydney Eye Hospital/Save Sight Institution

Sydney, New South Wales, Australia

Strathfield Retina Clinic

Sydney, New South Wales, Australia

Newcastle Eye Hospital Foundation

Waratah, New South Wales, Australia

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Adelaide Eye and Retina Centre

Adelaide, South Australia, Australia

Centre for Eye Research Australia (CERA)

Melbourne, Victoria, Australia

Retinology Institute

Melbourne, Victoria, Australia

Lions Eye Institute

Nedlands, Western Australia, Australia

Sydney Retina Clinic & Day Surgery

Sydney, , Australia

Countries

Australia

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

PQ-110-001

Identifier Type: -

Identifier Source: org_study_id