E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Atypical Hemolytic Uremic Syndrome (aHUS) |
Síndrome hemolítico urémico atípico (SHUa) |
|
E.1.1.1 | Medical condition in easily understood language |
Atypical Hemolytic Uremic Syndrome (aHUS) |
Síndrome hemolítico urémico atípico (SHUa) |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019515 |
E.1.2 | Term | Hemolytic uremic syndrome |
E.1.2 | System Organ Class | 100000004851 |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Efficacy of ALXN1210 |
Eficacia de ALXN1210 |
|
E.2.2 | Secondary objectives of the trial |
Safety and tolerability of ALXN1210 Additional efficacy measures |
Seguridad y tolerabilidad de ALXN1210 Medidas adicionales de eficacia |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female patients ≥ 12 years of age and weighing ≥ 40 kg at the time of consent. - Evidence of TMA, including low platelet count, hemolysis (breaking of red blood cells inside of blood vessels), and decreased kidney function. - Documented meningococcal vaccination not more than 3 years prior to dosing, under 18 also requiring vaccination against Streptococcus pneumoniae and Haemophilus influenzae - Female patients of childbearing potential must use highly effective contraception starting at screening and continuing until at least 8 months after the last dose of ALXN1210 |
- Pacientes hombres o mujeres ≥ 12 años de edad y de peso ≥ 40 kg en el momento del consentimiento. - Constancia de MAT, incluidas conteo bajo de plaquetas, hemólisis (Ruptura de glóbulos rojos de la sangre dentro de los vasos sanguíneos) e insuficiencia renal. - Vacunación frente a las infecciones meningocócicas documentada en los 3 años previos al inicio del tratamiento, Los pacientes < 18 años de edad deben haberse vacunado contra el el Streptococcus pneumoniae y la Haemophilus influenzae. - Las pacientes en edad fértil deben utilizar métodos anticonceptivos altamente eficaces a partir de la selección y continuando hasta al menos después de ocho meses de la última dosis de ALZX1210. |
|
E.4 | Principal exclusion criteria |
- ADAMTS13 deficiency (Activity < 5%) - Shiga toxin-related hemolytic uremic syndrome (STEC-HUS) - Streptococcal pneumonia-related hemolytic uremic syndrome (HUS) - Pregnancy or lactation - Identified drug exposure- related hemolytic uremic syndrome (HUS) - HUS related to bone marrow transplant (BMT)/hematopoietic stem cell transplant (HSCT) within last 90 days prior to start of Screening - HUS related to vitamin B12 deficiency - Systemic sclerosis (scleroderma), systemic lupus erythematosus (SLE), or antiphospholipid antibody positivity or syndrome - Chronic dialysis (defined as dialysis on a regular basis as renal replacement therapy for ESKD) |
- Deficiencia ADAMTS13 deficiency (Activitdad < 5%) - Síndrome hemolítico urémico relacionado con toxina Shiga (SHU-STEC). - Síndrome hemolítico urémico (SHU) relacionado con neumonía estreptocócica - Embarazo o lactancia. - Exposición al fármaco identificada- relacionada con el síndrome hemolítico urémico (SHU) - SHU relacionado con el transplante de médula osea (TMO)/trasplante de células madre hematopoyéticas (TCMH) en los últimos 90 días antes del inicio de la selección - SHU relacionado con una deficiencia de vitamina B12 - Esclerosis sistémica (esclerodermia), lupus eritematoso sistémico (LES), o síndrome antifosfolipídico o resultado positivo para anticuerpos antifosfolipídicos. - Diálisis crónica (definida como diálisis periódica como método de depuración renal para la nefropatía en etapa terminal). |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Completion of TMA Response |
Respuesta completa de la MAT |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
- Dialysis requirement status - Time to Complete TMA Response - Complete TMA Response status over time - Observed value and change from baseline in estimated glomerular filtration rate (eGFR) - Change from baseline in chronic kidney disease (CKD) stage - Change from baseline in hematologic parameters (platelets, LDH, hemoglobin) - Increase in hemoglobin of ≥ 20 g/L from baseline - Change from baseline in quality of life, as measured by the EQ-5D-3L (all patients), FACIT Fatigue Version 4 (patients ≥ 18 years of age), and Pediatric FACIT Fatigue (patients 12 to < 18 years of age) questionnaires |
- Estado de necesidad de diálisis. - Tiempo hasta la respuesta completa de la MAT. - Estado de la respuesta completa de la MAT a lo largo del tiempo. - Valor observado y cambio respecto al inicio en la tasa de filtración glomerular estimada (TFGe) - Cambio respecto al inicio en estadio de la nefropatía crónica - Cambio respecto al inicio en los parámetros hematológicos (plaquetas, LDH, hemoglobina) - Aumento de la hemoglobina de ≥ 20 g/l desde el inicio
- Cambio con respecto al inicio en la calidad de vida (CdV) medida mediante el cuestionario EQ-5D-3L (todos los pacientes) y los cuestionarios FACIT-fatigue versión 4 (pacientes ≥ 18 años de edad), y FACIT pediátrico cansancio (pacientes < 18 años de edad). |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | Yes |
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 | 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) | No |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 100 |
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 |
|
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
|
LVLS |
Última visita del último paciente |
|
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 | 1 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |