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 |
1.Uncontrolled diabetes mellitus as defined by HbA1c > 11.0% at screening 2. Presence or history of macular edema involving the center of the macula 3. Any kind of neovascular growth in the study eye, including anterior segment neovascularization 4. Arterial hypotension with systolic blood pressure < 100 or diastolic blood pressure < 60mmHg 5. ALT or Aspartate aminotransferase (AST) above 3 x Upper limit of normal (ULN) or bilirubin ≥ 1.5 ULN at screening, known ascites 6. Estimated glomerular filtration rate (eGFR CKD-EPI) below 30 ml/min/1.73 m^2 at screening 7. Any prior systemic anti-Vascular endothelial growth factor (VEGF) treatment or IVT anti-VEGF treatment in the study eye 8. Any prior intraocular steroid injection in the study eye 9. 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 10. Use of nitrates or NO donors (such as amyl nitrate) in any form including topical; PDE5 inhibitors, non-specific PDE inhibitors within 1 week or less than 5 half-lives (whichever is longer) 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 48 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 24 week of treatment in the study eye Frequency of treatment emergent adverse events |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
at 48 weeks 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 | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 39 |
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 |
United States |
Switzerland |
Bulgaria |
Czechia |
Denmark |
Latvia |
Netherlands |
Poland |
Portugal |
Romania |
Slovakia |
Spain |
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 | 25 |
E.8.9.1 | In the Member State concerned days | |
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 | 33 |