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 efficacy and safety of THR-317 administered in combination with ranibizumab, in subjects with central-involved DME (CI-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
- CI-DME with central subfield thickness of ≥ 320µm on Spectralis® SD-OCT or ≥ 305µm on non-Spectralis SD-OCT, in the study eye
- 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 (NPDR) of any stage in the study eye
- Written informed consent obtained from the subject prior to screening procedures |
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E.4 | Principal exclusion criteria |
- Macular oedema due to causes other than DME
- 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
- Change of the retinal architecture in the centre of the macula of the study eye that is likely to preclude improvement in BCVA following the resolution of DME
- Previous treatments / procedures as listed below, or their planned / expected use during the study period for up to 30 days after the last study treatment:
* Ranibizumab treatment in the study eye (any time for anti-VEGF naïve subjects; 1 month for subjects with a poor or no response to ranibizumab treatment)
* Bevacizumab treatment in the study eye (any time for anti-VEGF naïve subjects; 3 months for subjects with a poor or no response to ranibizumab treatment)
* Aflibercept treatment in the study eye (any time)
* Intraocular surgery in the study eye (3 months)
* Focal / grid laser photocoagulation in the study eye (3 months)
* Panretinal laser photocoagulation in the study eye (6 months)
* Intraocular or peri-ocular corticosteroids in the study eye (4 months)
* Ozurdex® (dexamethasone intravitreal implant) in the study eye (6 months)
* Other steroid implant in the study eye (any time)
* Systemic anti-VEGF treatment (3 months)
* Systemic corticosteroids (3 months)
- Aphakic study eye
- Uncontrolled glaucoma in the study eye
- More than 8D high myopia in the study eye
- Any active or suspected periocular / ocular / intraocular infection or inflammation in either eye
- Untreated diabetes
- Glycated haemoglobin A (HbA1c) > 12%
- Uncontrolled hypertension in the opinion of the Investigator
- Pregnant or lactating female
- Female of child-bearing potential not utilising an adequate form of contraception, or planning to become pregnant or to discontinue contraceptive precautions at any time during the entire study period
- Male of reproductive potential not utilising contraception |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in BCVA |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Incidence of systemic and ocular (serious) adverse events ([S]AEs), from first administration of study treatment up to the end of the study
- Change from baseline in BCVA, by study visit
- Change from baseline in CST, based on SD-OCT, as assessed by the CRC, by study visit
- Withdrawal from repeat study treatment and reason for withdrawal |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
From first administration of study treatment up 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 | Yes |
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 | No |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Ranibizumab 0.5 mg in combination with sham |
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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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 36 |
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 | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |