E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10051905 |
E.1.2 | Term | Coronavirus infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 impact of nangibotide on the progression of disease in patients receiving ventilatory support due to Covid-19 |
Evaluar el impacto de la nangibotida en la progresión de la enfermedad en pacientes que reciben ventilación asistida debido a la COVID-19 |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the effects of nangibotide exposure over 5 days in patients with Covid-19 • To evaluate the effect of nangibotide on clinical parameters • To evaluate the safety and tolerability of nangibotide in patients with COVID-19 • To evaluate PD relationship to TREM-1 pathway related markers • To evaluate the natural history of the disease regarding the activation of the TREM-1 pathways measured by soluble TREM-1 serum concentrations over time |
• Evaluar los efectos de la exposición a nangibotida durante 5 días en pacientes con COVID-19 • Evaluar el efecto de nangibotida en los parámetros clínicos • Evaluar la seguridad y tolerabilidad de nangibotida en pacientes con COVID-19 • Evaluar la relación farmacodinámica con los marcadores relacionados con la vía TREM-1 • Evaluar la historia natural de la enfermedad respecto a la activación de la vía TREM-1 medida por las concentraciones plasmáticas de TREM-1 soluble a lo largo del tiempo |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Provide written informed consent (emergency consent according to local regulations where approved) 2. Age 18 to 75 years (inclusive) 3. Admitted to an intensive care unit 4. Treatment with High Flow Nasal Oxygen, non-invasive ventilation or invasive mechanical ventilation for acute respiratory failure caused by COVID-19 for less than 48 hours 5. A PaO2:FiO2 ratio of <200mmHg (<26.7kPa) with a FiO2 ≥0.6 6. Confirmed laboratory diagnosis of COVID-19 within 7 days of meeting screening criteria |
1. Haber proporcionado el consentimiento informado (consentimiento de emergencia de acuerdo con la normativa local si está aprobado) 2. Edad entre 18 y 75 años (inclusive) 3. Ingresado en una unidad de cuidados intensivos 4. Tratamiento con oxígeno nasal de alto flujo, ventilación no invasiva o ventilación mecánica invasiva por insuficiencia respiratoria aguda causada por la COVID-19 durante menos de 48 horas 5. Una relación PaO2:FiO2 de <200 mmHg (<26,7 kPa) con una FiO2 ≥0,6 6. Diagnóstico de laboratorio confirmado de COVID-19 en un plazo de 7 días de cumplir los criterios de selección |
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E.4 | Principal exclusion criteria |
1. Known pregnancy (positive urine or serum pregnancy test) 2. Ongoing treatment with an immunomodulatory agent not included in the standard of care for COVID-19 (including participation in clinical trials of such agents) 3. Body mass index (BMI) ≥ 40 kg/m2 or weight ≥ 130 kg 4. Anticipated transfer to another hospital, which is not a study site within 72 hours 5. Expected to die within 6 months of treatment due to underlying chronic disease 6. Limitations of care in place during current hospital admission |
1. Embarazo conocido (prueba de embarazo positiva en orina o suero) 2. Tratamiento en curso con un inmunomodulador no incluido en el tratamiento de referencia para la COVID-19 (incluida la participación en ensayos clínicos de dichos inmunomoduladores) 3. Índice de masa corporal (IMC) ≥40 kg/m2 o peso ≥130 kg 4. Traslado anticipado a otro hospital, que no sea un centro del estudio en un plazo de 72 horas 5. Se espera que muera en los 6 meses siguientes al tratamiento debido a una enfermedad crónica subyacente 6. Limitaciones de atención implementadas durante el ingreso hospitalario actual |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Part 1: The incidence of adverse events and mortality until day 28 • Part 2: Clinical Status (7-point Ordinal Scale) assessed at Day 28 • Part 3: All-Cause mortality at day 28 |
• Parte 1 (inscripción completa): Incidencia de acontecimientos adversos y mortalidad hasta el día 28 • Parte 2: Estado clínico evaluado con la escala ordinal de 7 puntos el día 28 • Parte 3: Mortalidad por todas las causas el día 28 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From baseline to Day 28 |
Desde el momento basal hasta el día 28. |
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E.5.2 | Secondary end point(s) |
Additional Safety Parameters • The incidence of adverse events and mortality until day 28 • Safety laboratory tests (as part of routine clinical care): hematology, coagulation, plasma biochemistry • Adverse events (AEs), serious adverse events (SAEs) and deaths • Suspected adverse drug reactions (serious and non-serious)
Efficacy Parameters • Improvement of clinical status on each study day until day 14, at day 28 and at day 60 using an ordinal scale • Mortality at day 28 • PaO2:FiO2 ratio • Duration and nature of supported ventilation • Incidence of thromboembolic events • Incidence of secondary infection • Duration and nature of other organ support therapies • Functional status and mortality at day 60
Pharmacodynamics (exploratory) sTREM-1, inflammatory exploratory biomarkers |
Parámetros de seguridad adicionales • Incidencia de acontecimientos adversos y mortalidad hasta el día 28 • Análisis de laboratorio de seguridad (como parte de la atención clínica de rutina): hematología, coagulación, bioquímica en plasma • Acontecimientos adversos (AA), acontecimientos adversos graves (AAG) y muertes • Sospechas de reacciones adversas al medicamento (tanto graves como no graves)
Parámetros de eficacia • Mejoría del estado clínico cada día del estudio hasta el día 14, el día 28 y el día 60 utilizando una escala ordinal • Mortalidad el día 28 • Relación PaO2:FiO2 • Duración y naturaleza de la ventilación asistida • Incidencia de acontecimientos tromboembólicos • Incidencia de infección secundaria • Duración y naturaleza de otras terapias de soporte a órganos • Estado funcional y mortalidad el día 60
Farmacodinámica (exploratoria) sTREM-1, biomarcadores exploratorios de inflamación |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
From baseline to Day 60 |
Desde el momento basal hasta el día 60 |
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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 | No |
E.6.7 | Pharmacodynamic | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability |
Tolerabilidad |
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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) | Yes |
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 | 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 | Yes |
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 | 35 |
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 |
Belgium |
France |
Spain |
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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 study is defined as the last patient, last visit (LPLV). |
Último paciente última visita. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |