E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
diabetic macular oedema (DME) |
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E.1.1.1 | Medical condition in easily understood language |
Diabetic macular oedema is a swelling in the light-sensitive tissue in the back of the eye (called the retina) in people with diabetes, caused by leaking of blood vessels. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Eye Diseases [C11] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10057915 |
E.1.2 | Term | Diabetic macular oedema |
E.1.2 | System Organ Class | 100000004853 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10057934 |
E.1.2 | Term | Diabetic macular edema |
E.1.2 | System Organ Class | 100000004853 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the safety of 3 intravitreal injections of 2 dose levels of THR-317 (4mg or 8mg) and to assess its efficacy in improving best-corrected visual acuity (BCVA) and reducing central subfield thickness (CST), in subjects with centre-involved DME |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male or female aged 18 years or older
• Type 1 or type 2 diabetes
• Centre-involved DME with CST ≥ 340µm on Spectralis spectral domain optical coherence tomography (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 (20/40 and 20/320 Snellen equivalent) in the study eye
• Anti-VEGF treatment naïve study eye or poor response to prior anti-VEGF treatment in the study eye
• Non-proliferative diabetic retinopathy (NPDR) or stable proliferative diabetic retinopathy (PDR) without neovacularisation at the disc (NVD)
• Written informed consent obtained from the subject prior to screening procedures |
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E.4 | Principal 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 as listed below or their planned use during the THR-317 treatment period for up to 30 days after the last injection
Treatment / Procedure in Excluded Period prior to
the Study Eye Visit 2 (Day 0)
Panretinal or focal / grid laser 3 months
photocoagulation
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 4 months
corticosteroids
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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
• 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 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
up to 7-day follow-up visit after each injection |
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E.5.2 | Secondary end point(s) |
• Incidence of systemic and ocular (S)AEs up to the 30 day follow-up visit, after each injection and across injections per subject
• Incidence of systemic and ocular (S)AEs from first injection up to Day 90 and up to Day 150
• Proportion of subjects withdrawn from repeat injection and reason for withdrawal
• Proportion of subjects with a loss of ≥ 15, ≥ 10 or ≥ 5 ETDRS letters in BCVA from baseline by study visit
• 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
• Proportion of subjects with a ≥ 15 ETDRS letters gain in BCVA from baseline or ≥ 83 ETDRS letters, by study visit
• Mean change from baseline in BCVA, by study visit
• Mean change from baseline in CST, by study visit, based on SD-OCT |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
from baseline to end of study |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |