E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute Myocardial Infarction |
Infarto Agudo de Miocardio |
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E.1.1.1 | Medical condition in easily understood language |
Heart attack |
Infarto de miocardio |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10000891 |
E.1.2 | Term | Acute myocardial infarction |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
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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 assess the hepatic and renal safety of multiple dose administration of two dose levels of CSL112 (low dose [2 g] or high dose [6 g]) compared with placebo in subjects with acute myocardial infarction. |
Evaluar la seguridad y tolerabilidad hepáticas y renales de la administración de dosis múltiples de dos niveles de dosis de CSL112 (dosis baja [2 g] o dosis alta [6 g]) en comparación con placebo en pacientes con Infarto Agudo de Miocardio. |
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E.2.2 | Secondary objectives of the trial |
To examine the effect of CSL112 on the time-to-first occurrence of major adverse cardiovascular events (MACE), to characterize the safety and tolerability of CSL112, and to characterize the pharmacokinetics (PK) of CSL112 after multiple dose administration. |
Examinar el efecto de CSL112 sobre el tiempo hasta la primera aparición de acontecimientos adversos cardiovasculares graves (major adverse cardiovascular events, MACE), para caracterizar la seguridad y tolerabilidad de CSL112, y para caracterizar la farmacocinética (FC) de CSL112 después de la administración de dosis múltiples. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
To characterize the pharmacokinetics and pharmacodynamics of CSL112 after multiple dose administration |
Caracterizar la farmacocinética y la farmacodinamia de CSL112 después de la administración de dosis múltiples |
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E.3 | Principal inclusion criteria |
? Men or women, at least 18 years of age, with evidence of myocardial necrosis in a clinical setting consistent with a type I (spontaneous) acute myocardial infarction (AMI), in the last four days. |
Hombre o mujer, edad mínima de 18 años, indicios de necrosis miocárdica en un cuadro clínico compatible con un infarto agudo de miocardio de tipo I (espontáneo) infarto agudo de miocardio (IAM) en los últimos 4 días |
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E.4 | Principal exclusion criteria |
? Ongoing hemodynamic instability ? Evidence of hepatobiliary disease ? Evidence of chronic kidney disease (CKD) (Stage III, IV, or V), defined as moderate or severe renal impairment or if subject is receiving dialysis ? Evidence of unstable renal function ? History of acute kidney injury after previous exposure to an intravenous contrast agent. ? Known history of allergies, hypersensitivity or deficiencies to CSL112 or any of its components ? Other severe comorbid condition, concurrent medication, or other issue that renders the subject unsuitable for participation in the study |
?Inestabilidad hemodinámica continua ?Indicios de enfermedad hepatobiliar ?Indicios de ERC (estadios III, IV o V), definida como disfunción renal moderada o intensa o si el paciente está recibiendo diálisis. ?Indicios de enfermedad renal crónica ?Historial de insuficiencia renal aguda despues de una exposión prévia a un agente de contraste intravenoso. ?Antecedentes conocidos de alergias, hipersensibilidad o deficiencias a CSL112 o alguno de sus componentes. ?Otra patología comórbida grave, medicación concurrente u otro problema que haga que el paciente no sea adecuado para participar en el estudio. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Clinically important change in drug-induced liver injury defined as a change (from baseline) in alanine aminotransferase (ALT) greater than 3 times the upper limit of normal (ULN) or a change in total bilirubin greater than 2 times ULN, that is confirmed as determined upon repeat measurement.
- Clinically important change in renal status defined as a serum creatinine (Cr) increase to ? 1.5 x the baseline value, that is confirmed as determined upon repeat measurement or the need for renal replacement therapy. |
-Cambio clínicamente importante en la lesión inducida por fármacos definida cómo cambio (desde la visita basal) en alanina aminotransferasa (ALT) de más de 3 veces el límite superior de la normalidad (LSN) o un cambio en la bilirrubina total, superior a 2 veces el LSN, que se confirma según lo determina la repetición de la medición. -Cambio clínicamente significativo definido como aumento de la creatinina sérica hasta ?1,5 x el valor inicial confirmado tal como se ha determinado tras repetir la medición o la necesidad de tratamiento de diálisis. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From baseline (before 1st infusion) to Day 29. |
Desde la visita basal (antes de la 1º infusión) al día 29. |
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E.5.2 | Secondary end point(s) |
1. The time-to-first occurrence of a major adverse cardiovascular event (MACE). MACE includes: cardiovascular death, MI, ischemic stroke and hospitalization for unstable angina. 2. Pharmacokinetic profile (baseline-corrected plasma concentrations) of apolipoprotein A-I (apoA-I) and phosphatidylcholine (PC) 3. Plasma apoA-I and PC Cmax 4. Plasma apoA-I and PC Tmax 5. Plasma apoA-I and PC area under the curve (AUC) 6. Plasma apoA-I and PC t1/2 7. Plasma apoA-I and PC Clearance 8. Plasma apoA-I and PC Volume of distribution at steady state 9. The number of subjects with study-drug-related AEs 10. Overall AEs: total number of subjects with any AE 11. Bleeding events: number of subjects who experience bleeding events as defined by the Bleeding Academic Research Consortium (BARC) criteria (Mehran et al, 2011) 12. Immunogenic potential of CSL112: number of subjects with serum antibodies to CSL112 13. Change from baseline in serology: assessments (i.e., evidence of seroconversion or infection) will be conducted for hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) 1/2, parvovirus B19 14. Change from baseline in nucleic acid testing : assessments (i.e., evidence of seroconversion or infection) will be conducted for HAV, HBV, HCV, HIV 1/2, parvovirus B19 |
1. Tiempo hasta la primera aparición de acontecimiento adverso cardíaco grave (MACE). MACE incluye: Muerte cardiovascular, infarto de miocardio (IM), ictus isquémico y hospitalización por angina de pecho inestable.
2. Perfil farmacocinético (concentraciones plasmáticas basales corregidas) de la apolipoproteína AI (apoA-I) y de la fosfatidilcolina (PC) 3. Plasma apoA-I y PC Cmax 4. Plasma apoA-I y PC Tmax 5. Plasma de apoA-I y área de PC bajo la curva (AUC) 6. Plasma apoA-I y PC t1 / 2 7. Aclaramiento de Plasma apoA-I y PC 8. Volumen de distribución en estado de equilibrio de Plasma apoA-I y PC. 9. Número de pacientes con eventos adversos relacionados con el estudio del fármaco. 10. EAs Totales: número total de sujetos con cualquier RA 11. Episodios de sangrado: número de sujetos que experimentan episodios de sangrado como se define por la Bleeding Academic Research Consortium (BARC) criterios (Mehran et al, 2011) 12. Potencial inmunogénico de CSL112: número de sujetos con anticuerpos séricos contra CSL112 13. Cambio desde el inicio en la serología: evaluaciones (es decir, la evidencia de seroconversión o infección) se llevará a cabo para la hepatitis A (VHA), virus de hepatitis B (VHB), virus de la hepatitis C (VHC), virus de la inmunodeficiencia humana (VIH) 1/2 , parvovirus B19 14. Cambio desde el inicio de las pruebas de ácidos nucleicos: evaluaciones (es decir, la evidencia de seroconversión o infección) se llevará a cabo por el VHA, VHB, VHC, VIH 1/2, parvovirus B19 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. From the start of the first infusion up to 112 days after infusion 2.- 8.: Before and after the first and last infusions 9.- 11.: From the start of the infusion to the subject's end of study visit, up to approximately Day 382. 12.- 14.: Before infusion, and up to approximately Day 112 |
1. . Desde el comienzo de la primera perfusión hasta 112 días después de la infusión 2 - 8: Antes y después de la primera y última infusiones 9 - 11:... Desde el inicio de la infusión de la visita de estudio, hasta la visita final del estudio, aproximadamente Día 382. 12 - 14: Antes de la infusión, y hasta aproximadamente el día 112. |
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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 | Yes |
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 | 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 | 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 | 3 |
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 | 13 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 110 |
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 |
Australia |
Austria |
Bulgaria |
Canada |
Czech Republic |
Denmark |
France |
Germany |
Hungary |
Israel |
Italy |
Netherlands |
Poland |
Spain |
United Kingdom |
United States |
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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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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 | 10 |
E.8.9.1 | In the Member State concerned days | |
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 | 10 |