E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Paroxysmal Nocturnal Hemoglobinuria (PNH) |
emoglobinuria parossistica notturna (EPN) |
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E.1.1.1 | Medical condition in easily understood language |
Paroxysmal Nocturnal Hemoglobinuria (PNH) |
emoglobinuria parossistica notturna (EPN) |
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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 | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10055629 |
E.1.2 | Term | Paroxysmal nocturnal hemoglobinuria |
E.1.2 | System Organ Class | 100000004857 |
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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 |
efficacia di ALXN1210 |
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E.2.2 | Secondary objectives of the trial |
Safety and tolerability of ALXN1210 Additional efficacy measures |
sicurezza e tollerabilit¿ di ALXN1210 misure aggiuntive di efficacia |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female >= 18 years of age 2. Treated with eculizumab for PNH for at least 6 months prior to Day 1 3. Lactate dehydrogenase (LDH) <= 1.5 x upper limit of normal (ULN) at Screening 4. PNH diagnosis confirmed by documented by high-sensitivity flow cytometry 5. Documented meningococcal vaccination not more than 3 years prior to, or at the time of, initiating study treatment. 6. 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 7. Willing and able to give written informed consent and comply with study visit schedule |
1.Soggetto di sesso maschile o femminile = 18 anni di età 2.Trattamento con eculizumab per l’EPN da almeno 6 mesi prima del Giorno 1. 3.Lattato deidrogenasi (LDH) <= 1,5 volte il limite superiore della norma (ULN) allo Screening. 4.Diagnosi documentata di EPN, confermata dalla valutazione mediante citometria a flusso ad alta sensibilità 5.Documentata vaccinazione contro le infezioni da meningococco entro i 3 anni precedenti o nel momento in cui si inizia l’assunzione del farmaco dello studio. 6.Le pazienti in età fertile devono usare metodi altamente efficaci di contraccezione iniziando dallo screening e continuando fino almeno ad 8 mesi successivi all’ultima dose di ALXN1210 7.I pazienti devono essere disposti a e in grado di fornire un consenso informato scritto e rispettare tutte le visite dello studio |
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E.4 | Principal exclusion criteria |
1. History of bone marrow transplantation 2. Body weight < 40 kilograms 3. History of or ongoing major cardiac, pulmonary, renal, endocrine, or hepatic disease that, in the opinion of the investigator or sponsor, would preclude participation. 4. Unstable medical conditions (eg, myocardial ischemia, active gastrointestinal bleed, severe congestive heart failure, anticipated need for major surgery within 6 months of randomization, coexisting chronic anemia unrelated to PNH) 5. Females who are pregnant, breastfeeding or who have a positive pregnancy test at screening or Day 1 6. Participation in another interventional clinical study or use of any experimental therapy within 30 days before initiation of study drug on Day 1 in this study or within 5 half-lives of that investigational product, whichever is greater. |
1. Anamnesi di trapianto di midollo osseo. 2. Peso ponderale < 40 kg allo Screening. 3. Anamnesi o presenza di malattia cardiaca, polmonare, renale, endocrina o malattia epatica che, a giudizio dello Sperimentatore o dello Sponsor, precluda la partecipazione del paziente a una sperimentazione clinica 4.15. Condizioni cliniche instabili (ad es. ischemia miocardica, sanguinamento gastrointestinale attivo, insufficienza cardiaca congestizia grave, prevista necessità di intervento chirurgico maggiore entro 6 mesi dalla randomizzazione, anemia cronica coesistente non correlata all’EPN) che renderebbero improbabile la tolleranza dei pazienti ai requisiti previsti dal protocollo (ad es. le linee guida sulla trasfusione). 5. Soggetti di sesso femminile che presentano un test di gravidanza positivo allo screening o al Giorno 6. 20. Partecipazione a un altro studio di trattamento interventistico o uso di qualsiasi terapia sperimentale nei 30 giorni precedenti all’inizio della somministrazione del farmaco dello studio il Giorno 1 di questo studio o entro 5 emivite di quel prodotto sperimentale, a seconda di quale duri di più.
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E.5 End points |
E.5.1 | Primary end point(s) |
Hemolysis as directly measured by lactate dehydrogenase percent change (LDH-PCHG) |
Emolisi misurata direttamente tramite la variazione percentuale dei livelli di LDH |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Change from baseline in quality of life (QoL) as assessed by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue - Percentage of patients who achieve transfusion avoidance (TA) - Proportion of patients with stabilized hemoglobin |
- Variazione nella qualit¿ della vita (QoL) rilevata attraverso gli indici della valutazione funzionale della terapia di una malattia cronica (FACIT) Affaticamento - Percentuale di pazienti che evitano di ricevere la trasfusione - Percentuale di pazienti con emoglobina stabilizzata
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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 | Yes |
E.8.1.1 | Randomised | Yes |
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 | 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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
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 | Information not present in EudraCT |
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 |
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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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LVLS in the extension period |
LVLS nel periodo di estensione |
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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 |