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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04565756




Registration number
NCT04565756
Ethics application status
Date submitted
26/08/2020
Date registered
25/09/2020
Date last updated
10/01/2023

Titles & IDs
Public title
A Study to Evaluate the Safety and Tolerability of EXN407
Scientific 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
Secondary ID [1] 0 0
PQ-110-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetic Macular Edema 0 0
Condition category
Condition code
Eye 0 0 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - EXN407

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.

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.

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.

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


Treatment: Drugs: 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 code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Assessed starting from Day 1 of treatment to Day 36 in Dose Escalation.
Primary outcome [2] 0 0
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.
Timepoint [2] 0 0
Assessed starting from Day 1 of treatment to Day 113 in Dose Expansion phase.
Secondary outcome [1] 0 0
To evaluate the systemic pharmacokinetics of EXN407 ophthalmic solution in subjects with DMO secondary to diabetes mellitus by Tmax.
Timepoint [1] 0 0
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 outcome [2] 0 0
To evaluate the systemic pharmacokinetics of EXN407 ophthalmic solution in subjects with DMO secondary to diabetes mellitus by Cmax
Timepoint [2] 0 0
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 outcome [3] 0 0
To evaluate the systemic pharmacokinetics of EXN407 ophthalmic solution in subjects with DMO secondary to diabetes mellitus by AUC.
Timepoint [3] 0 0
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 outcome [4] 0 0
To evaluate the systemic pharmacokinetics of EXN407 ophthalmic solution in subjects with DMO secondary to diabetes mellitus by t½.
Timepoint [4] 0 0
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 outcome [5] 0 0
To evaluate the percentage (%) of changes in ocular functional measures as assessed using ophthalmoscopy.
Timepoint [5] 0 0
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 outcome [6] 0 0
To evaluate the percentage (%) of changes in ocular structural measures as assessed using ophthalmoscopy.
Timepoint [6] 0 0
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.

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Other
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
5/11/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
29/11/2022
Sample size
Target
Accrual to date
Final
48
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Macquarie University - Macquarie
Recruitment hospital [2] 0 0
Marsden Eye Specialists - Parramatta
Recruitment hospital [3] 0 0
Sydney Eye Hospital/Save Sight Institution - Sydney
Recruitment hospital [4] 0 0
Strathfield Retina Clinic - Sydney
Recruitment hospital [5] 0 0
Newcastle Eye Hospital Foundation - Waratah
Recruitment hospital [6] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [7] 0 0
Adelaide Eye and Retina Centre - Adelaide
Recruitment hospital [8] 0 0
Centre for Eye Research Australia (CERA) - Melbourne
Recruitment hospital [9] 0 0
Retinology Institute - Melbourne
Recruitment hospital [10] 0 0
Lions Eye Institute - Nedlands
Recruitment hospital [11] 0 0
Sydney Retina Clinic & Day Surgery - Sydney
Recruitment postcode(s) [1] 0 0
2109 - Macquarie
Recruitment postcode(s) [2] 0 0
2150 - Parramatta
Recruitment postcode(s) [3] 0 0
2000 - Sydney
Recruitment postcode(s) [4] 0 0
2135 - Sydney
Recruitment postcode(s) [5] 0 0
2298 - Waratah
Recruitment postcode(s) [6] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [7] 0 0
5000 - Adelaide
Recruitment postcode(s) [8] 0 0
3002 - Melbourne
Recruitment postcode(s) [9] 0 0
3146 - Melbourne
Recruitment postcode(s) [10] 0 0
6009 - Nedlands
Recruitment postcode(s) [11] 0 0
- Sydney

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Exonate Limited
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Novotech (Australia) Pty Limited
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04565756
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Mark Gillies, Prof
Address 0 0
Sydney Eye Hospital/Save Sight Institution
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries