Diabetic Macular Edema
Conditions
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.
Interventions
DRUGEXN407
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.
Sponsors
Novotech (Australia) Pty Limited
Exonate Limited
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | Assessed starting from Day 1 of treatment to Day 36 in Dose Escalation. | Number of Participants with Ocular Treatment Emergent Adverse Events (TEAEs) |
| 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. | Assessed starting from Day 1 of treatment to Day 113 in Dose Expansion phase. | Number of Participants with Ocular Treatment Emergent Adverse Events (TEAEs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | Measured by characterizing the PK profile by estimating the area under the curve (AUC) of EXN407 in plasma. |
| 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. | Measured by characterizing the PK profile by estimating the apparent elimination half-life (t½) of EXN407 in plasma. |
| 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. | Measured by characterizing the PK profile by estimating the time of the maximum plasma drug concentration (Tmax) of EXN407 in plasma. |
| To Evaluate Changes in Ocular Structural 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 up to 4 months(113 days) in Dose Expansion. | Measured by the changes from baseline in ophthalmic examination finding through ophthalmoscopy (corneal thickness). |
| 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. | Measured by the changes from baseline in ophthalmic examination finding through ophthalmoscopy (BCVA (Letters)) |
| 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. | Measured by characterizing the PK profile by estimating the maximum observed drug plasma concentration (Cmax) of EXN407 in plasma. |
Countries
Australia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dose Escalation EXN407 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.
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. | 3 |
| Dose Escalation EXN407 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.
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. | 3 |
| Dose Escalation EXN407 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.
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. | 3 |
| Dose Escalation Pooled Placebo Cohort Data from the placebo subjects in the 3 dose escalation groups was pooled giving a total of n=4 | 4 |
| Dose Expansion EXN407 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
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. | 23 |
| Dose Expansion Placebo Cohort Dose expansion cohort consisted of subjects randomised to receive EXN407 at the selected dose or placebo (vehicle) at a 2:1 drug: placebo ratio. | 12 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Dose Escalation EXN407 Cohort 1 | Dose Escalation EXN407 Cohort 2 | Dose Escalation EXN407 Cohort 3 | Dose Escalation Pooled Placebo Cohort | Dose Expansion EXN407 Cohort | Dose Expansion Placebo Cohort | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 60 years | 60 years | 67 years | 59 years | 63 years | 59 years | 61 years |
| BCVA | 83.3 BCVA (Letters) STANDARD_DEVIATION 3.51 | 83.0 BCVA (Letters) STANDARD_DEVIATION 1 | 71.3 BCVA (Letters) STANDARD_DEVIATION 1.53 | 86.3 BCVA (Letters) STANDARD_DEVIATION 5.56 | 81.3 BCVA (Letters) STANDARD_DEVIATION 6.04 | 83.6 BCVA (Letters) STANDARD_DEVIATION 7.44 | 82.1 BCVA (Letters) STANDARD_DEVIATION 6.54 |
| Corneal thickness | 561.3 microns STANDARD_DEVIATION 62.8 | 526.3 microns STANDARD_DEVIATION 10.02 | 581.7 microns STANDARD_DEVIATION 53.31 | 565.8 microns STANDARD_DEVIATION 25.86 | 555.6 microns STANDARD_DEVIATION 33.75 | 548.5 microns STANDARD_DEVIATION 38.35 | 553.2 microns STANDARD_DEVIATION 34.99 |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 3 Participants | 6 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized White | 3 Participants | 2 Participants | 2 Participants | 3 Participants | 18 Participants | 9 Participants | 37 Participants |
| Region of Enrollment Australia | 3 participants | 3 participants | 3 participants | 4 participants | 23 participants | 12 participants | 48 participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 7 Participants | 4 Participants | 14 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 3 Participants | 2 Participants | 16 Participants | 8 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 4 | 0 / 23 | 0 / 12 |
| other Total, other adverse events | 2 / 3 | 2 / 3 | 1 / 3 | 1 / 4 | 11 / 23 | 9 / 12 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 4 | 2 / 23 | 1 / 12 |
Outcome results
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.
Number of Participants with Ocular Treatment Emergent Adverse Events (TEAEs)
Time frame: Assessed starting from Day 1 of treatment to Day 36 in Dose Escalation.
Population: The Safety population comprised all randomised subjects who received any amount of study drug. Summaries, listings, and analyses were based on the treatment actually received. Screen failures and randomised subjects who did not receive any medication were excluded from the safety analysis set.~The Safety population was used for the summaries of all safety assessments.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Escalation EXN407 Cohort 1 Study Eye | 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. | 2 Participants |
| Dose Escalation EXN407 Cohort 1 Contralateral Eye | 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. | 2 Participants |
| Dose Escalation EXN407 Cohort 1, Bilateral Eye | 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. | 2 Participants |
| Dose Escalation EXN407 Cohort 2 Study Eye | 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. | 0 Participants |
| Dose Escalation EXN407 Cohort 2 Contralateral Eye | 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. | 1 Participants |
| Dose Escalation EXN407 Cohort 2 Bilateral Eye | 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. | 0 Participants |
| Dose Escalation EXN407 Cohort 3 Study Eye | 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. | 0 Participants |
| Dose Escalation EXN407 Cohort 3 Contralateral Eye | 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. | 0 Participants |
| Dose Escalation EXN407 Cohort 3 Bilateral Eye | 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. | 0 Participants |
| Pooled Placebo (Cohort 1, Cohort 2, Cohort 3) Study Eye | 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. | 0 Participants |
| Pooled Placebo (Cohort 1, Cohort 2, Cohort 3) Contralateral Eye | 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. | 0 Participants |
| Pooled Placebo (Cohort 1, Cohort 2, Cohort) Bilateral Eye | 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. | 0 Participants |
Comparison: Since the primary objective of the study was to evaluate ocular safety and tolerability, no formal hypothesis testing was performed for any continuous or categorical variables. All statistical analyses were descriptive in nature and any statistical inferences were carried out according to the analysis plan and interpreted in view of the exploratory nature of the study.
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.
Number of Participants with Ocular Treatment Emergent Adverse Events (TEAEs)
Time frame: Assessed starting from Day 1 of treatment to Day 113 in Dose Expansion phase.
Population: The Safety population comprised all randomised subjects who received any amount of study drug. Summaries, listings, and analyses were based on the treatment actually received. Screen failures and randomised subjects who did not receive any medication were excluded from the safety analysis set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Escalation EXN407 Cohort 1 Study Eye | 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. | 5 Participants |
| Dose Escalation EXN407 Cohort 1 Contralateral Eye | 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. | 3 Participants |
| Dose Escalation EXN407 Cohort 1, Bilateral Eye | 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. | 2 Participants |
| Dose Escalation EXN407 Cohort 2 Study Eye | 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. | 3 Participants |
| Dose Escalation EXN407 Cohort 2 Contralateral Eye | 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. | 1 Participants |
| Dose Escalation EXN407 Cohort 2 Bilateral Eye | 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. | 1 Participants |
Secondary
To Evaluate Changes in Ocular Functional Measures as Assessed Using Ophthalmoscopy.
Measured by the changes from baseline in ophthalmic examination finding through ophthalmoscopy (BCVA (Letters))
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose Escalation EXN407 Cohort 1 Study Eye | To Evaluate Changes in Ocular Functional Measures as Assessed Using Ophthalmoscopy. | -5.0 BCVA (Letters) | Standard Deviation 8.72 |
| Dose Escalation EXN407 Cohort 1 Contralateral Eye | To Evaluate Changes in Ocular Functional Measures as Assessed Using Ophthalmoscopy. | -5.0 BCVA (Letters) | Standard Deviation 9.54 |
| Dose Escalation EXN407 Cohort 1, Bilateral Eye | To Evaluate Changes in Ocular Functional Measures as Assessed Using Ophthalmoscopy. | -2.0 BCVA (Letters) | Standard Deviation 2.65 |
| Dose Escalation EXN407 Cohort 2 Study Eye | To Evaluate Changes in Ocular Functional Measures as Assessed Using Ophthalmoscopy. | -1.0 BCVA (Letters) | Standard Deviation 3.61 |
| Dose Escalation EXN407 Cohort 2 Contralateral Eye | To Evaluate Changes in Ocular Functional Measures as Assessed Using Ophthalmoscopy. | 3.0 BCVA (Letters) | Standard Deviation 2 |
| Dose Escalation EXN407 Cohort 2 Bilateral Eye | To Evaluate Changes in Ocular Functional Measures as Assessed Using Ophthalmoscopy. | -4.0 BCVA (Letters) | Standard Deviation 7.94 |
| Dose Escalation EXN407 Cohort 3 Study Eye | To Evaluate Changes in Ocular Functional Measures as Assessed Using Ophthalmoscopy. | -1.3 BCVA (Letters) | Standard Deviation 3.3 |
| Dose Escalation EXN407 Cohort 3 Contralateral Eye | To Evaluate Changes in Ocular Functional Measures as Assessed Using Ophthalmoscopy. | -3.0 BCVA (Letters) | Standard Deviation 5.35 |
| Dose Escalation EXN407 Cohort 3 Bilateral Eye | To Evaluate Changes in Ocular Functional Measures as Assessed Using Ophthalmoscopy. | -0.1 BCVA (Letters) | Standard Deviation 3.54 |
| Pooled Placebo (Cohort 1, Cohort 2, Cohort 3) Study Eye | To Evaluate Changes in Ocular Functional Measures as Assessed Using Ophthalmoscopy. | -1.7 BCVA (Letters) | Standard Deviation 6.06 |
| Pooled Placebo (Cohort 1, Cohort 2, Cohort 3) Contralateral Eye | To Evaluate Changes in Ocular Functional Measures as Assessed Using Ophthalmoscopy. | 1.3 BCVA (Letters) | Standard Deviation 5.14 |
| Pooled Placebo (Cohort 1, Cohort 2, Cohort) Bilateral Eye | To Evaluate Changes in Ocular Functional Measures as Assessed Using Ophthalmoscopy. | 1.3 BCVA (Letters) | Standard Deviation 5.31 |
Secondary
To Evaluate Changes in Ocular Structural Measures as Assessed Using Ophthalmoscopy.
Measured by the changes from baseline in ophthalmic examination finding through ophthalmoscopy (corneal thickness).
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose Escalation EXN407 Cohort 1 Study Eye | To Evaluate Changes in Ocular Structural Measures as Assessed Using Ophthalmoscopy. | -5.0 corneal thickness (microns) | Standard Deviation 6.93 |
| Dose Escalation EXN407 Cohort 1 Contralateral Eye | To Evaluate Changes in Ocular Structural Measures as Assessed Using Ophthalmoscopy. | -2.7 corneal thickness (microns) | Standard Deviation 8.33 |
| Dose Escalation EXN407 Cohort 1, Bilateral Eye | To Evaluate Changes in Ocular Structural Measures as Assessed Using Ophthalmoscopy. | 15.3 corneal thickness (microns) | Standard Deviation 7.02 |
| Dose Escalation EXN407 Cohort 2 Study Eye | To Evaluate Changes in Ocular Structural Measures as Assessed Using Ophthalmoscopy. | 11.0 corneal thickness (microns) | Standard Deviation 19.08 |
| Dose Escalation EXN407 Cohort 2 Contralateral Eye | To Evaluate Changes in Ocular Structural Measures as Assessed Using Ophthalmoscopy. | -3.0 corneal thickness (microns) | Standard Deviation 4 |
| Dose Escalation EXN407 Cohort 2 Bilateral Eye | To Evaluate Changes in Ocular Structural Measures as Assessed Using Ophthalmoscopy. | -10.3 corneal thickness (microns) | Standard Deviation 18.93 |
| Dose Escalation EXN407 Cohort 3 Study Eye | To Evaluate Changes in Ocular Structural Measures as Assessed Using Ophthalmoscopy. | -0.8 corneal thickness (microns) | Standard Deviation 3.77 |
| Dose Escalation EXN407 Cohort 3 Contralateral Eye | To Evaluate Changes in Ocular Structural Measures as Assessed Using Ophthalmoscopy. | 1.3 corneal thickness (microns) | Standard Deviation 4.5 |
| Dose Escalation EXN407 Cohort 3 Bilateral Eye | To Evaluate Changes in Ocular Structural Measures as Assessed Using Ophthalmoscopy. | 0.2 corneal thickness (microns) | Standard Deviation 8.61 |
| Pooled Placebo (Cohort 1, Cohort 2, Cohort 3) Study Eye | To Evaluate Changes in Ocular Structural Measures as Assessed Using Ophthalmoscopy. | 0.1 corneal thickness (microns) | Standard Deviation 10.52 |
| Pooled Placebo (Cohort 1, Cohort 2, Cohort 3) Contralateral Eye | To Evaluate Changes in Ocular Structural Measures as Assessed Using Ophthalmoscopy. | 2.4 corneal thickness (microns) | Standard Deviation 11.27 |
| Pooled Placebo (Cohort 1, Cohort 2, Cohort) Bilateral Eye | To Evaluate Changes in Ocular Structural Measures as Assessed Using Ophthalmoscopy. | 0.5 corneal thickness (microns) | Standard Deviation 11.35 |
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.
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.
Population: Number of participants with detectable values were analyzed. Limited quantifiable concentration-time data was available for this study, as such the plasma PK characteristics of EXN407, in particular the dose dependency, could not be comprehensively characterised. In the low dose group (0.5 mg/mL), PK parameters could not be determined due to a lack of quantifiable concentration-time data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose Escalation EXN407 Cohort 1 Study Eye | To Evaluate the Systemic Pharmacokinetics of EXN407 Ophthalmic Solution in Subjects With DMO Secondary to Diabetes Mellitus by AUC. | NA hr*ng/mL | — |
| Dose Escalation EXN407 Cohort 1 Contralateral Eye | To Evaluate the Systemic Pharmacokinetics of EXN407 Ophthalmic Solution in Subjects With DMO Secondary to Diabetes Mellitus by AUC. | 0.0368 hr*ng/mL | Standard Deviation 0 |
| Dose Escalation EXN407 Cohort 1, Bilateral Eye | To Evaluate the Systemic Pharmacokinetics of EXN407 Ophthalmic Solution in Subjects With DMO Secondary to Diabetes Mellitus by AUC. | 0.153 hr*ng/mL | Standard Deviation 0.205 |
| Dose Escalation EXN407 Cohort 2 Study Eye | To Evaluate the Systemic Pharmacokinetics of EXN407 Ophthalmic Solution in Subjects With DMO Secondary to Diabetes Mellitus by AUC. | 0.0845 hr*ng/mL | Standard Deviation 0.112 |
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.
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.
Population: Number of participants with detectable values were analyzed. Limited quantifiable concentration-time data was available for this study, as such the plasma PK characteristics of EXN407, in particular the dose dependency, could not be comprehensively characterised. In the low dose group (0.5 mg/mL), PK parameters could not be determined due to a lack of quantifiable concentration-time data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose Escalation EXN407 Cohort 1 Study Eye | To Evaluate the Systemic Pharmacokinetics of EXN407 Ophthalmic Solution in Subjects With DMO Secondary to Diabetes Mellitus by Cmax | NA ng/mL | — |
| Dose Escalation EXN407 Cohort 1 Contralateral Eye | To Evaluate the Systemic Pharmacokinetics of EXN407 Ophthalmic Solution in Subjects With DMO Secondary to Diabetes Mellitus by Cmax | 0.0571 ng/mL | Standard Deviation 0 |
| Dose Escalation EXN407 Cohort 1, Bilateral Eye | To Evaluate the Systemic Pharmacokinetics of EXN407 Ophthalmic Solution in Subjects With DMO Secondary to Diabetes Mellitus by Cmax | 0.0831 ng/mL | Standard Deviation 0.0253 |
| Dose Escalation EXN407 Cohort 2 Study Eye | To Evaluate the Systemic Pharmacokinetics of EXN407 Ophthalmic Solution in Subjects With DMO Secondary to Diabetes Mellitus by Cmax | 0.0883 ng/mL | Standard Deviation 0.041 |
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.
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.
Population: Number of participants with detectable values were analyzed. Limited quantifiable concentration-time data was available for this study, as such the plasma PK characteristics of EXN407, in particular the dose dependency, could not be comprehensively characterised. In the low dose group (0.5 mg/mL), PK parameters could not be determined due to a lack of quantifiable concentration-time data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose Escalation EXN407 Cohort 1 Study Eye | To Evaluate the Systemic Pharmacokinetics of EXN407 Ophthalmic Solution in Subjects With DMO Secondary to Diabetes Mellitus by t½. | NA hour | — |
| Dose Escalation EXN407 Cohort 1 Contralateral Eye | To Evaluate the Systemic Pharmacokinetics of EXN407 Ophthalmic Solution in Subjects With DMO Secondary to Diabetes Mellitus by t½. | 0 hour | Standard Deviation 0 |
| Dose Escalation EXN407 Cohort 1, Bilateral Eye | To Evaluate the Systemic Pharmacokinetics of EXN407 Ophthalmic Solution in Subjects With DMO Secondary to Diabetes Mellitus by t½. | 0 hour | Standard Deviation 0 |
| Dose Escalation EXN407 Cohort 2 Study Eye | To Evaluate the Systemic Pharmacokinetics of EXN407 Ophthalmic Solution in Subjects With DMO Secondary to Diabetes Mellitus by t½. | 0 hour | Standard Deviation 0 |
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.
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.
Population: Number of participants with detectable values were analyzed. Limited quantifiable concentration-time data was available for this study, as such the plasma PK characteristics of EXN407, in particular the dose dependency, could not be comprehensively characterised. In the low dose group (0.5 mg/mL), PK parameters could not be determined due to a lack of quantifiable concentration-time data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose Escalation EXN407 Cohort 1 Study Eye | To Evaluate the Systemic Pharmacokinetics of EXN407 Ophthalmic Solution in Subjects With DMO Secondary to Diabetes Mellitus by Tmax. | NA hour | — |
| Dose Escalation EXN407 Cohort 1 Contralateral Eye | To Evaluate the Systemic Pharmacokinetics of EXN407 Ophthalmic Solution in Subjects With DMO Secondary to Diabetes Mellitus by Tmax. | 0.5 hour | Standard Deviation 0 |
| Dose Escalation EXN407 Cohort 1, Bilateral Eye | To Evaluate the Systemic Pharmacokinetics of EXN407 Ophthalmic Solution in Subjects With DMO Secondary to Diabetes Mellitus by Tmax. | 0.5 hour | Standard Deviation 1.23e-10 |
| Dose Escalation EXN407 Cohort 2 Study Eye | To Evaluate the Systemic Pharmacokinetics of EXN407 Ophthalmic Solution in Subjects With DMO Secondary to Diabetes Mellitus by Tmax. | 0.494 hour | Standard Deviation 0.276 |