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| Name | Class |
|---|---|
| Novotech (Australia) Pty Limited | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| 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. |
|
| 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| 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 |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Macquarie University | Macquarie | New South Wales | 2109 | Australia | ||
| Marsden Eye Specialists |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| FG002 | 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. |
| FG003 | Dose Escalation Pooled Placebo Cohort | Data from the placebo subjects in the 3 dose escalation groups was pooled giving a total of n=4 |
| FG004 | 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. |
| FG005 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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) | 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. | Posted | Count of Participants | Participants | Assessed starting from Day 1 of treatment to Day 36 in Dose Escalation. |
|
Each subject in the Dose Escalation cohorts (numbered Cohorts 1, 2, 3, etc.) received EXN407 or vehicle BID over a 7-day period Each subject in the Dose Expansion received EXN407 or vehicle BID over an 84-day period
Assessed starting from Day 1 of treatment to Day 36 in Dose Expansion phase. Assessed starting from Day 1 of treatment to Day 113 in Dose Expansion phase. Arms/Groups are combined (not separated into study eye and fellow eye) as both ocular and non-ocular adverse events are reported.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Angina pectoris | Cardiac disorders | MedDRA v23.1 | Systematic Assessment | single instance of moderate angina pectoris (atypical chest pain) that was assessed as unlikely related to the study drug. The study drug was interrupted, and the event resolved within 23 days |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Blepharitis | Eye disorders | MedDRA v23.1 | Systematic Assessment | 1 subject in the 0.5 mg/mL EXN407 cohort (#108-001) had 1 event of mild seborrheic blepharitis (bilateral affecting both eyes) |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Loic Lhuillier | Exonate | +44 (0)1223 734716 | loic.lhuillier@exonate.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 28, 2022 | Oct 15, 2024 | Prot_SAP_000.pdf |
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| 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. |
| 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. |
| 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. |
| 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)) | 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. |
| 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). | 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. |
| Helene Cass, Dr |
| Marsden Eye Specialists |
| Principal Investigator |
| Lily Ooi | Princess Alexandra Hospital | Principal Investigator |
| Parramatta |
| New South Wales |
| 2150 |
| Australia |
| Sydney Eye Hospital/Save Sight Institution | Sydney | New South Wales | 2000 | Australia |
| Strathfield Retina Clinic | Sydney | New South Wales | 2135 | Australia |
| Newcastle Eye Hospital Foundation | Waratah | New South Wales | 2298 | Australia |
| Princess Alexandra Hospital | Woolloongabba | Queensland | 4102 | Australia |
| Adelaide Eye and Retina Centre | Adelaide | South Australia | 5000 | Australia |
| Centre for Eye Research Australia (CERA) | Melbourne | Victoria | 3002 | Australia |
| Retinology Institute | Melbourne | Victoria | 3146 | Australia |
| Lions Eye Institute | Nedlands | Western Australia | 6009 | Australia |
| Sydney Retina Clinic & Day Surgery | Sydney | Australia |
| Protocol Violation |
|
| 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. |
| BG002 | 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. |
| BG003 | Dose Escalation Pooled Placebo Cohort | Data from the placebo subjects in the 3 dose escalation groups was pooled giving a total of n=4 |
| BG004 | 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. |
| BG005 | 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. |
| BG006 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| BCVA | Mean | Standard Deviation | BCVA (Letters) |
|
| Corneal thickness | Mean | Standard Deviation | microns |
|
| OG001 | Dose Escalation EXN407 Cohort 1 Contralateral Eye | 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. |
| OG002 | Dose Escalation EXN407 Cohort 1, Bilateral Eye | 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. |
| OG003 | Dose Escalation EXN407 Cohort 2 Study Eye | 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. |
| OG004 | Dose Escalation EXN407 Cohort 2 Contralateral Eye | 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. |
| OG005 | Dose Escalation EXN407 Cohort 2 Bilateral Eye | 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. |
| OG006 | Dose Escalation EXN407 Cohort 3 Study Eye | 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. |
| OG007 | Dose Escalation EXN407 Cohort 3 Contralateral Eye | 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. |
| OG008 | Dose Escalation EXN407 Cohort 3 Bilateral Eye | 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. |
| OG009 | Pooled Placebo (Cohort 1, Cohort 2, Cohort 3) Study Eye | Data from the placebo subjects was pooled (as appropriate). |
| OG010 | Pooled Placebo (Cohort 1, Cohort 2, Cohort 3) Contralateral Eye | Data from the placebo subjects was pooled (as appropriate). |
| OG011 | Pooled Placebo (Cohort 1, Cohort 2, Cohort) Bilateral Eye | Data from the placebo subjects was pooled (as appropriate). |
|
|
|
| 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) | 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. | Posted | Count of Participants | Participants | 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. | 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. | Posted | Mean | Standard Deviation | hour | 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. | 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. | Posted | Mean | Standard Deviation | ng/mL | 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. |
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|
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| 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. | 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. | Posted | Mean | Standard Deviation | hr*ng/mL | 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. |
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|
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| 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. | 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. | Posted | Mean | Standard Deviation | hour | 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. |
|
|
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| 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)) | Posted | Mean | Standard Deviation | BCVA (Letters) | 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. |
|
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| 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). | Posted | Mean | Standard Deviation | corneal thickness (microns) | 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. |
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| 0 |
| 3 |
| 0 |
| 3 |
| 2 |
| 3 |
| EG001 | 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. | 0 | 3 | 0 | 3 | 2 | 3 |
| EG002 | 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. | 0 | 3 | 0 | 3 | 1 | 3 |
| EG003 | Dose Escalation Pooled Placebo Cohort | Data from the placebo subjects in the 3 dose escalation groups was pooled giving a total of n=4 | 0 | 4 | 0 | 4 | 1 | 4 |
| EG004 | 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. | 0 | 23 | 2 | 23 | 11 | 23 |
| EG005 | 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. | 0 | 12 | 1 | 12 | 9 | 12 |
|
| non-ST elevation acute coronary syndrome | Cardiac disorders | MedDRA v23.1 | Systematic Assessment | single instance of severe acute coronary syndrome (non-ST elevation acute coronary syndrome) that was assessed as unlikely related to the study drug. The study drug was interrupted, and the event resolved within 10 days. |
|
| severe hypoglycaemia | Metabolism and nutrition disorders | MedDRA v23.1 | Systematic Assessment | single instance of severe hypoglycaemia (severe hypoglycaemia) that was assessed as unlikely related to the study drug. The study drug was not changed, and the event resolved within 1 day without treatment. |
|
|
| Posterior capsule opacification | Eye disorders | MedDRA v23.1 | Systematic Assessment | 1 subject in the 1.0 mg/mL group (#109-004) had 1 event of right posterior capsule opacification (bilateral affecting both eyes). |
|
| Vision blurred | Eye disorders | MedDRA v23.1 | Systematic Assessment | 1 subject in the 0.5 mg/mL EXN407 cohort (#106-006) had 1 event of blurred vision in mornings (bilateral affecting both eyes). |
|
| Eye pruritus | Eye disorders | MedDRA v23.1 | Systematic Assessment | 2 subjects in the EXN407 group (#103-009 and #108-018) had 2 events (1 event each in study eye) of eye pruritis (left itchy eye and right itchy eye, respectively). |
|
| Hypoglycemia | Metabolism and nutrition disorders | MedDRA v23.1 | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA v23.1 | Systematic Assessment |
|
| COVID-19 | Infections and infestations | MedDRA v23.1 | Systematic Assessment |
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| C-reactive protein increased | Investigations | MedDRA v23.1 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA v23.1 | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA v23.1 | Systematic Assessment |
|
| Episcleritis | Eye disorders | MedDRA v23.1 | Systematic Assessment | Episcleritis. 1 subject in the placebo group (#112-006) had 1 event of episcleritis right eye (study eye). |
|
| Dizziness | Nervous system disorders | MedDRA v23.1 | Systematic Assessment | Dizziness |
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| Lower respiratory tract infection | Respiratory, thoracic and mediastinal disorders | MedDRA v23.1 | Systematic Assessment |
|
| Gastrointestinal infection | Infections and infestations | MedDRA v23.1 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA v23.1 | Systematic Assessment |
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| Otitis media | Infections and infestations | MedDRA v23.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA v23.1 | Systematic Assessment |
|
| Visual field defect | Nervous system disorders | MedDRA v23.1 | Systematic Assessment |
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| Migraine | Nervous system disorders | MedDRA v23.1 | Systematic Assessment |
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| Blood phosphorus decreased | Investigations | MedDRA v23.1 | Systematic Assessment |
|
| Electrocardiogram ST segment elevation | Investigations | MedDRA v23.1 | Systematic Assessment |
|
| Punctate keratiis | Eye disorders | MedDRA v23.1 | Systematic Assessment | 1 subject in the placebo group (#108-024) had 1 event of punctate epithelial erosions right eye (study eye). |
|
| Foreign body sensation in eyes | Eye disorders | MedDRA v23.1 | Systematic Assessment | 1 subject in the placebo group (#112-002) had 1 event of foreign body sensation right eye (study eye). |
|
| Cataract cortical | Eye disorders | MedDRA v23.1 | Systematic Assessment | 1 subject in the placebo group (#108-015) had 1 event of increase in degree of cortical cataract (bilateral affecting both eyes). |
|
| Eye irritation | Eye disorders | MedDRA v23.1 | Systematic Assessment | 1 subject in the placebo group (#112-002) had 1 event of irritation - right eye (study eye). |
|
| Hyperglycemia | Metabolism and nutrition disorders | MedDRA v23.1 | Systematic Assessment |
|
| Sinus bradycardia | Cardiac disorders | MedDRA v23.1 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA v23.1 | Systematic Assessment |
|
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA v23.1 | Systematic Assessment |
|
| Acrochordon | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA v23.1 | Systematic Assessment |
|
Not provided
Not provided