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 |
- Retinopatia diabética não proliferativa (RDNP): fase inicial de uma condição clínica em que ocorre lesão na retina devido à diabetes mellitus (DM)
- A DM caracteriza-se por níveis aumentados de açúcar no sangue |
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E.1.1.1 | Medical condition in easily understood language |
Non-proliferative diabetic retinopathy |
Retinopatia diabética não proliferativa |
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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 |
Estabelecer a prova de conceito para a eficácia de runcaciguat no tratamento da RDNP |
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E.2.2 | Secondary objectives of the trial |
To investigate the safety and tolerability of runcaciguat in patients with NPDR |
Investigar a segurança e a tolerabilidade de runcaciguat em doentes com RDNP |
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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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1. RDNP moderadamente grave a grave no olho em estudo: níveis 47 ou 53 na escala de gravidade da retinopatia diabética (DRSS)
2. Diabetes tipo 1 ou 2
3. Melhor acuidade visual corrigida (MAVC) em letras da escala ETDRS (Early Treatment Diabetic Retinopathy Study) no olho em estudo = 69 letras (aproximadamente equivalente a 20/40 ou superior na escala de Snellen) |
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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 m^2 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 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 |
Diabetes mellitus não controlada definida por HbA1c > 11.0%, no momento da seleção
Presença ou história de edema macular com envolvimento do centro da mácula
Qualquer tipo de crescimento neovascular no olho em estudo, incluindo neovascularização do segmento anterior
Hipotensão arterial com pressão arterial sistólica <100 ou pressão arterial diastólica <60mmHg;
Hipotensão arterial com pressão arterial sistólica < 100 Alanina aminotransferase (ALT) ou Aspartato aminotransferase (AST) 3x acima do limite superior normal (LSN) ou bilirrubina = 1,5 LSN no momento da seleção ou no Dia 1, ascite conhecida;
Taxa de filtração glomerular estimada (eTFG CKD-EPI) inferior a 30 ml/min/1,73 m2 no momento da seleção
Qualquer tratamento sistémico prévio com anti-fator de crescimento vascular endotelial (VEGF) ou tratamento anti-VEGF intravítreo no olho em estudo
Qualquer injeção intraocular prévia de esteroides no olho em estudo
Qualquer tratamento prévio de fotocoagulação laser focal ou em grelha num raio de 500 micrómetros do centro da fóvea ou qualquer tratamento prévio de fotocoagulação panretiniana (PRP) no olho em estudo
Utilização de nitratos ou dadores de NO (como o nitrato de amilo) sob qualquer forma, incluindo tópica; inibidores da PDE5, inibidores não específicos das PDE na semana anterior ou num período inferior a 5 semividas (o que for mais longo) antes da primeira administração do medicamento do estudo |
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E.5 End points |
E.5.1 | Primary end point(s) |
Diabetic Retinpathy Severity Scale (DRSS) improvment ≥2 steps at 24 Weeks of treatment in the study eye |
Melhoria da classificação de gravidade da retinopatia diabética (DRSS) ≥2 graus após 24 semanas de tratamento no olho do ensaio |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
24 weeks after treatment |
24 semanas após o tratamento |
|
E.5.2 | Secondary end point(s) |
Vision threatening complications at 48 weeks of treatment
DRSS improvement ≥2 steps at 48 Weeks of treatment
Frequency of treatment emergent adverse events |
Complicações com risco de perda da visão após 48 semanas de tratamento
Melhoria da classificação de gravidade da retinopatia diabética (DRSS) ≥ 2 graus após 48 semanas de tratamento
Frequência de acontecimentos adversos emergentes do tratamento |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
at 48 weeks of treatment
at 48 weeks of treatment
from first administration till 28 days after the last dose of the treatment |
após 48 semanas de tratamento
após 48 semanas de tratamento
após a primeira administração até 28 dias após a última dose do tratamento |
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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 | 50 |
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 |
Czechia |
Denmark |
Germany |
Hungary |
Netherlands |
Poland |
Portugal |
Spain |
Switzerland |
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
|
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). |
O final do estudo a nível global define-se como a data da última consulta do último participante no estudo em todos os centros e em todos os países participantes (UE e não UE).
|
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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 | 33 |
E.8.9.2 | In all countries concerned by the trial days | 0 |