A Study to Evaluate the Safety and Tolerability of EXN407

Diabetic Macular Edema Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04565756
• Other study ID #: PQ-110-001
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: November 5, 2020
• Est. completion date: November 29, 2022

Study information

• Verified date: January 2023
• Source: Exonate Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: November 29, 2022
• Est. primary completion date: October 25, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 ß-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.

Related Conditions & MeSH terms

• Diabetic Macular Edema
• Macular Edema

Intervention

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.

Locations

Country	Name	City	State
Australia	Adelaide Eye and Retina Centre	Adelaide	South Australia
Australia	Macquarie University	Macquarie	New South Wales
Australia	Centre for Eye Research Australia (CERA)	Melbourne	Victoria
Australia	Retinology Institute	Melbourne	Victoria
Australia	Lions Eye Institute	Nedlands	Western Australia
Australia	Marsden Eye Specialists	Parramatta	New South Wales
Australia	Strathfield Retina Clinic	Sydney	New South Wales
Australia	Sydney Eye Hospital/Save Sight Institution	Sydney	New South Wales
Australia	Sydney Retina Clinic & Day Surgery	Sydney
Australia	Newcastle Eye Hospital Foundation	Waratah	New South Wales
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland

Sponsors (2)

Lead Sponsor	Collaborator
Exonate Limited	Novotech (Australia) Pty Limited

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Measured by frequency and severity of ocular AEs in the study and contralateral eyes.	Assessed starting from Day 1 of treatment to Day 36 in Dose Escalation.
Primary	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.	Measured by frequency and severity of ocular AEs in the study and contralateral eyes.	Assessed starting from Day 1 of treatment to Day 113 in Dose Expansion phase.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	To evaluate the percentage (%) of changes in ocular functional measures as assessed using ophthalmoscopy.	Measured by the changes from baseline in ophthalmic examination finding through ophthalmoscopy.	From Day 1 of Treatment to End of Treatment i.e. assessed upto 36 Days in Dose Escalation and upto 4 months(113 days) in Dose Expansion.
Secondary	To evaluate the percentage (%) of changes in ocular structural measures as assessed using ophthalmoscopy.	Measured by the changes from baseline in ophthalmic examination finding through ophthalmoscopy.	From Day 1 of Treatment to End of Treatment i.e. assessed upto 36 Days in Dose Escalation and upto 4 months(113 days) in Dose Expansion.