A Study to Evaluate the Safety and Efficacy of THR-317 for the Treatment of Diabetic Macular Oedema (DME)

Study Overview
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Brief Summary
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This study is conducted to evaluate the safety of THR-317 when administered intravitreally and to assess the compound's efficacy in improving best-corrected visual acuity (BCVA) and reducing central subfield thickness (CST) in subjects with centre-involved diabetic macular oedema (DME).

Official Title
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A Phase 2, Single-masked, Multicentre Study to Evaluate the Safety and Efficacy of 2 Dose Levels of THR-317 for the Treatment of Diabetic Macular Oedema (DME)

Conditions
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Diabetic Retinopathy, Macular Edema

Intervention / Treatment
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* Drug: Anti-PlGF recombinant monoclonal antibody, 4mg dose
* Drug: Anti-PlGF recombinant monoclonal antibody, 8mg dose


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Male or female aged 18 years or older Type 1 or type 2 diabetes Centre-involved DME with CST ≥ 340µm on Spectralis SD-OCT or ≥ 320µm on non-Spectralis SD OCT, in the study eye Reduced vision primarily due to DME, with BCVA between 72 and 23 ETDRS letters read at 4 meters (20/40 and 20/320 Snellen equivalent) in the study eye Anti-vascular endothelial growth factor (anti-VEGF) treatment naïve study eye or poor response to prior anti-VEGF treatment in the study eye Non-proliferative diabetic retinopathy, or stable proliferative diabetic retinopathy without neovacularisation at the disc Written informed consent obtained from the subject prior to screening procedures Exclusion criteria: Concurrent disease in the study eye, other than DME, that could compromise BCVA, require medical or surgical intervention during the study period or could confound interpretation of the results Previous treatments / procedures in the study eyes as follows, or their planned use during the THR-317 treatment period for up to 30 days after the last injection: panretinal or focal / grid laser photocoagulation [3 months], anti-VEGF treatment [any time for anti-VEGF naïve subjects; 4 weeks for subjects with a poor response to anti-VEGF treatment], intra-ocular or peri-ocular corticosteroids [4 months], steroid implant [any time], intra-ocular surgery [3 months], vitrectomy [any time] Any active ocular / intra-ocular infection or inflammation in either eye Aphakic study eye Untreated diabetes Glycated haemoglobin A (HbA1c) > 12% Uncontrolled hypertension in the opinion of the Investigator Pregnant or lactating female or female of child-bearing potential not utilising an adequate form of contraception or male of reproductive potential not utilising contraception suggesting lens / zonular instability

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: THR-317 4mg<br>anti-PlGF recombinant monoclonal antibody, 4mg dose | Drug: Anti-PlGF recombinant monoclonal antibody, 4mg dose<br>* 3 intravitreal injections of THR-317 4mg approximately 1 month apart<br>|
| Experimental: THR-317 8mg<br>anti-PlGF recombinant monoclonal antibody, 8mg dose | Drug: Anti-PlGF recombinant monoclonal antibody, 8mg dose<br>* 3 intravitreal injections of THR-317 8mg approximately 1 month apart<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of acute (up to the 7-day follow-up visit) ocular (serious) adverse events ([S]AEs) in the study eye, after each injection and across injections per subject |  | up to the 7-day follow-up visit after each injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of systemic and ocular (S)AEs up to the 30-day follow-up visit, after each injection and across injections per subject |  | up to the 30-day follow-up visit after each injection | 
| Incidence of systemic and ocular (S)AEs from first injection up to Day 90 and up to Day 150 |  | From day 0 to day 150 | 
| Proportion of subjects withdrawn from repeat injection and reason for withdrawal |  | At day 30 and at day 60 | 
| Proportion of subjects with a loss of ≥ 15, ≥ 10 or ≥ 5 ETDRS letters in BCVA from baseline by study visit |  | Up to day 150 | 
| Proportion of subjects with an acute loss (up to the 7-day follow-up visit) of ≥ 15, ≥ 10 or ≥ 5 ETDRS letters in BCVA after each injection |  | Up to 7-day follow-up visit after each injection | 
| Proportion of subjects with a ≥ 15 ETDRS letters gain in BCVA from baseline or ≥ 83 ETDRS letters, by study visit |  | Up to day 150 | 
| Mean change from baseline in BCVA, by study visit |  | Up to day 150 | 
| Mean change from baseline in CST, by study visit, based on spectral domain optical coherence tomography (SD-OCT), as assessed by the central reading centre (CRC) |  | Up to day 150 |