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A Study to Evaluate the Safety and Tolerability of EXN407

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ClinicalTrials.gov Identifier: NCT04565756
Recruitment Status : Recruiting
First Posted : September 25, 2020
Last Update Posted : June 9, 2021
Sponsor:
Collaborator:
Novotech (Australia) Pty Limited
Information provided by (Responsible Party):
Exonate Limited

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 approximate Snellen equivalent 20/32 (6/9, 78 letters) in the study eye, which is considered secondary to diabetes mellitus. For brevity, the BCVA criteria will be noted as 20/32 (6/9).

This study will provide a basis for further clinical development of EXN407 ophthalmic solution.


Condition or disease Intervention/treatment Phase
Diabetic Macular Edema Drug: EXN407 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : November 5, 2020
Estimated Primary Completion Date : November 15, 2021
Estimated Study Completion Date : May 20, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Edema

Arm Intervention/treatment
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.
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.

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.
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.

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.
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.

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
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.




Primary Outcome Measures :
  1. 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. [ Time Frame: Assessed starting from Day 1 of treatment to Day 36 in Dose Escalation. ]
    Measured by frequency and severity of ocular AEs in the study and contralateral eyes.

  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 Expansion phase. [ Time Frame: Assessed starting from Day 1 of treatment to Day 113 in Dose Expansion phase. ]
    Measured by frequency and severity of ocular AEs in the study and contralateral eyes.


Secondary Outcome Measures :
  1. To evaluate the systemic pharmacokinetics of EXN407 ophthalmic solution in subjects with DMO secondary to diabetes mellitus by Tmax. [ 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. ]
    Measured by characterizing the PK profile by estimating the time of the maximum plasma drug concentration (Tmax) of EXN407 in plasma.

  2. To evaluate the systemic pharmacokinetics of EXN407 ophthalmic solution in subjects with DMO secondary to diabetes mellitus by Cmax [ 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. ]
    Measured by characterizing the PK profile by estimating the maximum observed drug plasma concentration (Cmax) of EXN407 in plasma.

  3. To evaluate the systemic pharmacokinetics of EXN407 ophthalmic solution in subjects with DMO secondary to diabetes mellitus by AUC. [ 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. ]
    Measured by characterizing the PK profile by estimating the area under the curve (AUC) of EXN407 in plasma.

  4. To evaluate the systemic pharmacokinetics of EXN407 ophthalmic solution in subjects with DMO secondary to diabetes mellitus by t½. [ 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. ]
    Measured by characterizing the PK profile by estimating the apparent elimination half-life (t½) of EXN407 in plasma.

  5. To evaluate the percentage (%) of changes in ocular functional measures as assessed using ophthalmoscopy. [ Time Frame: 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. ]
    Measured by the changes from baseline in ophthalmic examination finding through ophthalmoscopy.

  6. To evaluate the percentage (%) of changes in ocular structural measures as assessed using ophthalmoscopy. [ Time Frame: 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. ]
    Measured by the changes from baseline in ophthalmic examination finding through ophthalmoscopy.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subject is at least 18 years of age inclusive, at the time of signing the informed consent.
  2. BCVA better than approximate Snellen equivalent 20/32 (6/9, 78 letters) in the study eye using the ETDRS visual acuity scale at Screening. Subjects should have less than a 10% variance in this measure 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. Prior or current use of intravitreal ranibizumab, bevacizumab, aflibercept or the use of systemic or intraocular steroids in either eye.
  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04565756


Contacts
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Contact: Mike Taylor 01223734710 Mike.Taylor@exonate.com

Locations
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Australia, Australian Capital Territory
Adelaide Eye and Retina Centre Recruiting
Adelaide, Australian Capital Territory, Australia, 5000
Contact: Kerin Haywood    +0882123022    khaywood@adelaideeye.com.au   
Principal Investigator: Jolly Gilmore, A/Prof         
Australia, New South Wales
Macquarie University Recruiting
Macquarie, New South Wales, Australia, 2109
Contact: Ray Yung    +61298122979    ray.yung@mq.edu.au   
Principal Investigator: Rohan Merani, Dr         
Marsden Eye Specialists Recruiting
Parramatta, New South Wales, Australia, 2150
Contact: Trish Forsyth    +61296357077    trish.forsyth@marsdeneye.com   
Principal Investigator: Helene Cass, Dr         
Sydney Eye Hospital/Save Sight Institution Recruiting
Sydney, New South Wales, Australia, 2000
Contact: Sharon McKenzie    +61293827309    sharon.mckenzie@sydney.edu.au   
Principal Investigator: Mark Gillies, Prof         
Strathfield Retina Clinic Recruiting
Sydney, New South Wales, Australia, 2135
Contact: Jessica Shen    +61297462988    jessica.shen@strathfieldretina.com.au   
Principal Investigator: Hemal Mehta, Dr         
Newcastle Eye Hospital Foundation Recruiting
Waratah, New South Wales, Australia, 2298
Contact: Lyn Emery    02 4967 6777    lyn@huntereyesurgeons.com.au   
Principal Investigator: Peter Davies, Dr         
Australia, Victoria
Centre for Eye Research Australia (CERA) Recruiting
Melbourne, Victoria, Australia, 3002
Contact: Thuy Chau    +61399298076    thuy.chau@unimelb.edu.au   
Principal Investigator: Sanjeewa Wickremasinghe, Prof         
Retinology Institute Recruiting
Melbourne, Victoria, Australia, 3146
Contact: Cleopatra Mhlanga    +61449087807    ctm@zave.com.au   
Principal Investigator: Wilson Heriot, A/Prof         
Australia, Western Australia
Lions Eye Institute Recruiting
Nedlands, Western Australia, Australia, 6009
Contact: Tammy Corica    +61893810829    tammycorica@lei.org.au   
Principal Investigator: Fred Chen, Dr         
Australia
Sydney Retina Clinic & Day Surgery Recruiting
Sydney, Australia
Contact: EUGENIA CHU    +612 9221 1637    mailto:echu@sydneyretina.com.au   
Sponsors and Collaborators
Exonate Limited
Novotech (Australia) Pty Limited
Investigators
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Principal Investigator: 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: Gerald Liew,, A/Prof South West Retina
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
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Responsible Party: Exonate Limited
ClinicalTrials.gov Identifier: NCT04565756    
Other Study ID Numbers: PQ-110-001
First Posted: September 25, 2020    Key Record Dates
Last Update Posted: June 9, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Macular Edema
Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases