E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
- Non-proliferative diabetic retinopathy: early stage of a medical condition in which damage occurs to the retina due to diabetes mellitus (DM) - DM is characterized by too much sugar in the blood |
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E.1.1.1 | Medical condition in easily understood language |
Non-proliferative diabetic retinopathy |
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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 | 10054109 |
E.1.2 | Term | Non-proliferative diabetic retinopathy |
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 establish the proof-of-concept for the efficacy of runcaciguat in the treatment of NPDR |
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E.2.2 | Secondary objectives of the trial |
To investigate the safety and tolerability of runcaciguat in patients with NPDR |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Moderately severe to severe NPDR in the study eye: Diabetic Retinopathy Severity Scale (DRSS) levels 47 or 53 2. Diabetes type 1 or 2 3. Best corrected visual aquity (BCVA) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score in the study eye of ≥69 letters (approximate Snellen equivalent of 20/40 or better)
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E.4 | Principal exclusion criteria |
- Uncontrolled diabetes mellitus as defined by HbA1c > 11.0% at screening - Presence or history of macular edema involving the center of the macula - Any kind of neovascular growth in the study eye, including anterior segment neovascularization - Arterial hypotension with systolic blood pressure < 100 or diastolic blood pressure < 60mmHg - ALT or AST above 3 x ULN or bilirubin ≥ 1.5 ULN at screening, known ascites - Estimated glomerular filtration rate (eGFR CKD-EPI) below 30 ml/min/1.73 m2 at screening - Any prior systemic anti-Vascular endothelial growth factor (VEGF) treatment or IVT anti-VEGF treatment in the study eye - Any prior intraocular steroid injection in the study eye - Any prior grid or focal laser photocoagulation within 500 microns of the foveal center or any prior Pan-retinal photocoagulation (PRP) in the study eye - Use of nitrates or Nitric oxide (NO) donors (such as amyl nitrate) in any form including topical; Phosphodiesterase 5 (PDE5) inhibitors, non-specific PDE inhibitors within 1 week before first study drug administration
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E.5 End points |
E.5.1 | Primary end point(s) |
Diabetic Retinopathy Severity Scale (DRSS) improvement ≥2 steps at 24 Weeks of treatment in the study eye
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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) |
Vision threatening complications at 48 week of treatment DRSS improvement ≥2 steps at 48 week of treatment Frequency of treatment emergent adverse events |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
at 48 week of treatment from first administration till 28 days after the last dose of the treatment |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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 | No |
E.8.1.4 | Double blind | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 5 |
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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 43 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
United States |
Latvia |
Poland |
Bulgaria |
Netherlands |
Romania |
Spain |
Switzerland |
Czechia |
Denmark |
Portugal |
Slovakia |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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The end of the study as a whole is defined as the date of the last visit of the last subject in the study in all sites and in all participating countries (EU and non-EU). |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 33 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 36 |
E.8.9.2 | In all countries concerned by the trial days | 0 |