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 | 19.1 |
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 de eficacia adicionales |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients from birth up to < 18 years of age and weighing ≥ 5 kg at the time of consent. 2. Evidence of thrombotic microangiopathy (TMA), including low platelet count, hemolysis (breaking of red blood cells inside of blood vessels), and decreased kidney function. 3. Documented meningococcal vaccination not more than 3 years prior to dosing, and vaccination against Streptococcus pneumoniae and Haemophilus influenzae 4. 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 |
1. Pacientes desde el momento de su nacimiento hasta una edad < 18 años y que pesen ≥ 5 kg en el momento del consentimiento. 2. Evidencia de microangiopatía trombótica (MAT), que incluya trombocitopenia, hemólisis (rotura de los globulos rojos en los vaos sanguíneos) y disminución de la función renal 3. Vacuna documentada frente a las infecciones meningocócicas en los 3 años previos al inicio del tratamiento, y haberse vacunado contra Haemophilus influenzae (Hib) y el Streptococcus pneumoniae 4. Las mujeres en edad fértil deben utilizar medidas anticonceptivas efectivas desde la selección y durante 8 meses después de la última dosis de ALXN1210 |
|
E.4 | Principal exclusion criteria |
1. ADAMTS13 deficiency (Activity < 5%) 2. Shiga toxin-related hemolytic uremic syndrome (STEC-HUS) 3. Positive direct Coombs test 4. Pregnancy or breastfeeding 5. Identified drug exposure-related hemolytic uremic syndrome (HUS) 6. Bone marrow transplant (BMT)/hematopoietic stem cell transplant (HSCT) within last 6 months prior to start of Screening 7. HUS related to vitamin B12 deficiency 8. Systemic sclerosis (scleroderma), systemic lupus erythematosus (SLE), or antiphospholipid antibody positivity or syndrome 9. Chronic dialysis (defined as dialysis on a regular basis as renal replacement therapy for ESKD) |
1. Deficiencia de ADAMTS13 (actividad < 5 %) 2. Síndrome hemolítico urémico relacionado con toxina Shiga (SHU-TS) 3. Prueba directa de Coombs positiva. 4. Embarazo o periodo de lactancia. 5. Identificación de SHU relacionado con la exposición a fármacos. 6. Trasplante de médula ósea (TMO)/trasplante de células madre hematopoyéticas (TCMH) en los últimos 6 meses antes del inicio de la selección. 7. SHU relacionado con una deficiencia de vitamina B12. 8. Esclerodermia, lupus eritematoso sistémico (LES), o síndrome antifosfolipídico o resultado positivo para anticuerpos antifosfolipídicos. 9. 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) |
Complete TMA Response |
Respuesta completa de 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 Pediatric FACIT Fatigue questionnaire (patients ≥ 5 years of age) |
- 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 desde el inicio en la FGe. - Estadio de la nefropatía crónica en comparación con el valor inicial. - Valor observado y cambio desde el inicio de los parámetros hematológicos (plaquetas, LDH, hemoglobina). - Aumento en los niveles de hemoglobina de ≥ 20 g/l desde el inicio - Cambio desde el inicio en la CdV, según la medición del cuestionario FACIT de cansancio en población pediátrica (pacientes de edad ≥ 5 años). |
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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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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 in the extension period |
LVLS en el periodo de extensión |
|
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 | 6 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |