A Study to Evaluate the Safety and Tolerability of EXN407

NCT04565756 | Completed Phase 1 Results

• 1 other identifier: PQ-110-001
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 11

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.

Conditions

Diabetic Macular Edema

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (6)

• To Evaluate the Systemic Pharmacokinetics of EXN407 Ophthalmic Solution in Subjects With DMO Secondary to Diabetes Mellitus by Tmax.

  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

  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.

  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.

  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.

  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.

Study Arms (4)

Dose Escalation Cohort 1

EXPERIMENTAL

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

Dose Escalation Cohort 2

EXPERIMENTAL

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

Dose Escalation Cohort 3

EXPERIMENTAL

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

Dose Expansion Cohort

EXPERIMENTAL

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

Interventions

EXN407 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 1; Dose Escalation Cohort 2; Dose Escalation Cohort 3; Dose Expansion Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject is at least 18 years of age inclusive, at the time of signing the informed consent.
• 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.
• Ocular media is consistent with SD-OCT imaging and cataracts are not expected in the subject for the duration of the study.
• The subject has no other retinal disease.
• 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.

You may not qualify if:

• Any other retinal disease in the study eye, other than centre involved DMO or diabetic retinopathy.
• Poor vision (VA 6/60 or worse) in the contralateral eye.
• Intraocular inflammation (including trace or greater) in the study eye. History of idiopathic or autoimmune uveitis in either eye.
• 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).
• 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).
• History of (within 90 days of Screening date) cerebral vascular accident (stroke) or MI.
• Significant renal impairment including subjects on chronic renal dialysis and subjects with a history of nephrectomy or kidney transplant (regardless of renal function).
• History of anaphylaxis, anaphylactoid (resembling anaphylaxis) reactions, or severe allergic responses.
• 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.
• Known to have, or history of a positive test result for, hepatitis B or C, HIV, syphilis, tuberculosis, or COVID-19.

Sponsors & Collaborators

• Exonate Limited: lead
• Novotech (Australia) Pty Limited: collaborator

Study Sites (11)

Macquarie University

Macquarie, New South Wales, 2109, Australia

Location

Marsden Eye Specialists

Parramatta, New South Wales, 2150, Australia

Location

Sydney Eye Hospital/Save Sight Institution

Sydney, New South Wales, 2000, Australia

Location

Strathfield Retina Clinic

Sydney, New South Wales, 2135, Australia

Location

Newcastle Eye Hospital Foundation

Waratah, New South Wales, 2298, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

Location

Adelaide Eye and Retina Centre

Adelaide, South Australia, 5000, Australia

Location

Centre for Eye Research Australia (CERA)

Melbourne, Victoria, 3002, Australia

Location

Retinology Institute

Melbourne, Victoria, 3146, Australia

Location

Lions Eye Institute

Nedlands, Western Australia, 6009, Australia

Location

Sydney Retina Clinic & Day Surgery

Sydney, Australia

Location

Results Point of Contact

• Title: Loic Lhuillier
• Organization: Exonate

loic.lhuillier@exonate.com

+44 (0)1223 734716

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2020
• First Posted: September 25, 2020
• Study Start: November 5, 2020
• Primary Completion: October 25, 2022
• Study Completion: November 29, 2022
• Last Updated: May 9, 2025
• Results First Posted: May 9, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

AU (11)