A Study to Evaluate THR-149 Treatment for Diabetic Macular Oedema

Study Overview
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Brief Summary
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Part A of the study is conducted to select the THR-149 dose level. Part B of the study is conducted to assess the efficacy and safety of the selected dose level compared to aflibercept, up to Month 3. As from Month 3, in about half of the subjects, the effect of a single flip-over injection (aflibercept or THR-149) will be evaluated when administered 1 month after the 3 monthly injections of THR-149 or aflibercept. In the other subjects, the durability of 3 monthly injections of THR 149 or aflibercept will be evaluated.

Official Title
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A Phase 2, Randomised, Multicentre Study to Assess the Dose Level of Multiple THR-149 Injections and to Evaluate the Efficacy and Safety of THR-149 Versus Aflibercept for the Treatment of Diabetic Macular Oedema (DME)

Conditions
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Diabetes Mellitus, Diabetic Retinopathy, Diabetic Macular Edema

Intervention / Treatment
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* Drug: THR-149 dose level 1
* Drug: THR-149 dose level 2
* Drug: THR-149 dose level 3
* Drug: THR-149 0.13mg
* Drug: THR-149 0.13mg + aflibercept 2mg
* Drug: aflibercept 2mg + THR-149 0.13mg
* Drug: Aflibercept 2mg


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Written informed consent obtained from the subject prior to screening procedures Male or female aged 18 years or older at the time of signing the informed consent Type 1 or type 2 diabetes BCVA ETDRS letter score ≤ 73 and ≥ 39 in the study eye (for subjects in Part A); BCVA ETDRS letter score ≤ 73 and ≥ 24 in the study eye (for subjects in Part B) Central involved DME (CI-DME) with CST of ≥ 320µm in men or ≥ 305µm in women, on spectral domain optical coherence tomography (SD-OCT), in the study eye Received ≥ 5 anti-vascular endothelial growth factor (anti-VEGF) injections for the treatment of CI-DME BCVA ETDRS letter score ≥ 34 in the fellow eye Key Exclusion Criteria: Macular edema due to causes other than DME in the study eye Concurrent disease in the study eye, other than central-involved DME, that could require medical or surgical intervention during the study period or could confound interpretation of the results Any condition that could confound the ability to detect the efficacy of the investigational medicinal product Previous confounding medications / interventions, or their planned administration Presence of neovascularisation at the disc in the study eye Presence of iris neovascularisation in the study eye Uncontrolled glaucoma in the study eye Any active or suspected ocular or periocular infection, or active intraocular inflammation, in either eye Untreated Diabetes Mellitus Glycated haemoglobin A (HbA1c) > 12% Uncontrolled hypertension

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: THR-149 dose level 1<br> | Drug: THR-149 dose level 1<br>* 3 intravitreal injections of THR-149 dose level 1, 1 month apart<br>|
| Experimental: THR-149 dose level 2<br> | Drug: THR-149 dose level 2<br>* 3 intravitreal injections of THR-149 dose level 2, 1 month apart<br>|
| Experimental: THR-149 dose level 3<br> | Drug: THR-149 dose level 3<br>* 3 intravitreal injections of THR-149 dose level 3, 1 month apart<br>|
| Experimental: THR-149 + sham<br> | Drug: THR-149 0.13mg<br>* 3 intravitreal injections of THR-149 0.13mg (selected dose level), 1 month apart, followed after 1 month by a sham (pretend) injection<br>|
| Experimental: THR-149 + aflibercept flip-over<br> | Drug: THR-149 0.13mg + aflibercept 2mg<br>* 3 intravitreal injections of THR-149 0.13mg (selected dose level), 1 month apart, followed after 1 month by an intravitreal injection of aflibercept 2mg<br>|
| Active Comparator: Aflibercept + THR-149 flip-over<br> | Drug: aflibercept 2mg + THR-149 0.13mg<br>* 3 intravitreal injections of aflibercept 2mg, 1 month apart, followed after 1 month by an intravitreal injection of THR-149 0.13mg (selected dose level)<br>|
| Active Comparator: Aflibercept + sham<br> | Drug: Aflibercept 2mg<br>* 3 intravitreal injections of aflibercept 2mg, 1 month apart, followed after 1 month by a sham (pretend) injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in best-corrected visual acuity (BCVA) ETDRS letter score from Baseline, in subjects in Part B of the study |  | At Month 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in BCVA ETDRS letter score from Baseline, by study visit |  | Up to Month 6 | 
| Mean change in central subfield thickness (CST) from Baseline, by study visit |  | Up to Month 6 | 
| Incidence of systemic and ocular adverse events (AEs) and serious adverse events (SAEs) |  | Up to Month 6 |