E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Atypical Hemolytic Uremic Syndrome (aHUS) |
syndrome hémolytique et urémique atypique (SHUa) |
|
E.1.1.1 | Medical condition in easily understood language |
Atypical Hemolytic Uremic Syndrome (aHUS) |
syndrome hémolytique et urémique atypique (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 | 20.0 |
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 |
Efficacité de ALXN1210 |
|
E.2.2 | Secondary objectives of the trial |
Safety and tolerability of ALXN1210
Additional efficacy measures |
Sécurité d'emploi et tolerance de ALXN1210
Mesures d'efficacité additionnelles |
|
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. Patients de la naissance à < 18 ans et pesant ≥ 5 kg au moment du consentement.
2. Preuve de MAT, comprenant des thrombopénies, des preuves d’hémolyse et d’atteinte rénale
3. les patients doivent avoir été vaccinés contre les infections à méningocoques dans les 3 ans avant le début du traitement et doivent avoir été vaccinés contre l’Haemophilus influenzae et contre le Streptococcus pneumonia
4. Les patientes en âge d’avoir des enfants doivent suivre les directives indiquées dans le protocole quant à la prévention des grossesses durant le traitement et 8 mois après la dernière administration du produit à l’étude |
|
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. Déficit héréditaire connu ou acquis en « désintégrines et métalloprotéases avec domaines de thrombospondine de type 1, treizième membre » (ADAMTS13) (activité < 5 %).
2. Syndrome hémolytique et urémique lié à la toxine de Shiga connu,
3. Test de Coombs direct positif.
4. Grossesse ou allaitement.
5. Identification d’un SHU lié à une exposition médicamenteuse.
6. Greffe de moelle osseuse/Greffe de cellules souches hématopoïétiques dans les 6 derniers mois précédant le début de la sélection.
7. SHU lié à une carence en vitamine B12. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Complete TMA Response |
Réponse complète des 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) |
- Evaluation des besoins en matière de dialyse
- Délai jusqu’à une réponse complète des MAT
- Réponse complète des MAT au fil du temps
- Valeur observée et variation par rapport à la référence du DFGe
- Evaluation du stade de l’IRC,
- Valeur observée et variation par rapport à la référence des paramètres hématologiques (plaquettes, LDH, hémoglobine)
- Augmentation de l’hémoglobine ≥ 20 g/l par rapport à la référence observée 8
- Changement de la QdV par rapport à la référence, mesuré par le questionnaire FACIT-Fatigue en pédiatrie (patients de ≥ 5 ans) |
|
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 | 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 |
|
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 | 5 |
E.8.9.1 | In the Member State concerned days | 10 |
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 |