A Study to Evaluate THR-317 and Ranibizumab Combination Treatment for 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 intravitreal THR-317 administered in combination with ranibizumab, and to assess the efficacy of the combination treatment in improving best-corrected visual acuity (BCVA) and reducing central subfield thickness (CST), in subjects with central-involved diabetic macular oedema (CI-DME).

Official Title
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A Phase 2, Randomised, Single-masked, Active-controlled, Multicentre Study to Evaluate the Efficacy and Safety of Intravitreal THR-317 Administered in Combination With Ranibizumab, for the Treatment of Diabetic Macular Oedema (DME)

Conditions
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Diabetes Mellitus, Diabetic Retinopathy, Macular Edema

Intervention / Treatment
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* Drug: Ranibizumab 0.5mg
* Drug: THR-317 8mg
* Drug: Sham injection


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 Mellitus CI-DME with central subfield thickness of ≥ 320μm on Spectralis® SD-OCT or ≥ 305μm on non Spectralis SD-OCT, in the study eye Anti-vascular endothelial growth factor (anti-VEGF) treatment naïve study eye, or poor or no response to prior treatment with ranibizumab in the study eye Reduced vision primarily due to DME, with BCVA ≤ 72 and ≥ 23 ETDRS letter score (≤ 20/40 and ≥ 20/320 Snellen equivalent) in the study eye Non-proliferative diabetic retinopathy of any stage in the study eye Written informed consent obtained from the subject prior to screening procedures Exclusion Criteria: Concurrent disease in the study eye, other than CI-DME, that could compromise BCVA, require medical or surgical intervention during the study period or could confound interpretation of the results Previous confounding treatments / procedures, or their planned / expected use during the study period for up to 30 days after the last administration of study treatment Any active ocular / intraocular infection or inflammation in either eye Aphakic study eye Poorly controlled Diabetes Mellitus Uncontrolled hypertension 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

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: Ranibizumab + THR-317<br>Subjects will receive intravitreal ranibizumab in combination with THR-317 | Drug: Ranibizumab 0.5mg<br>* 3 intravitreal injections of ranibizumab 0.5mg, approximately 1 month apart<br>* Other names: Lucentis®;Drug: THR-317 8mg<br>* 3 intravitreal injections of THR-317 8mg, approximately 1 month apart<br>|
| Active Comparator: Sham + ranibizumab<br>Subjects will receive a sham injection in combination with intravitreal ranibizumab | Drug: Ranibizumab 0.5mg<br>* 3 intravitreal injections of ranibizumab 0.5mg, approximately 1 month apart<br>* Other names: Lucentis®;Drug: Sham injection<br>* 3 sham injections, approximately 1 month apart. No actual injections. No medication is used.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in BCVA |  | At Day 84 (Month 3) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of systemic and ocular adverse events including serious adverse events |  | From Day 0 to Day 140 | 
| Change from baseline in BCVA, by study visit |  | From Day 0 to Day 140 | 
| Change from baseline in CST, based on spectral domain optical coherence tomography (SD-OCT), as assessed by the central reading centre, by study visit |  | From Screening to Day 140 | 
| Withdrawal from repeat study treatment and reason for withdrawal | Number of subjects meeting withdrawal criteria from repeat study treatment | At Day 28 and at Day 56 |