E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Paroxysmal Nocturnal Hemoglobinuria |
Emoglobinuria parossistica notturna |
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E.1.1.1 | Medical condition in easily understood language |
Paroxysmal Nocturnal Hemoglobinuria |
Emoglobinuria parossistica notturna |
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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 |
To evaluate PK noninferiority of ravulizumab SC versus ravulizumab IV in adult patients with PNH. |
Valutare la non inferiorità della farmacocinetica di ravulizumab sc contro ravulizumab IV in pazienti adulti con PNH. |
|
E.2.2 | Secondary objectives of the trial |
- To characterize PK of ravulizumab SC - To characterize PD of ravulizumab SC - To characterize immunogenicity of ravulizumab SC - To evaluate HRQoL and treatment satisfaction on ravulizumab SC - To evaluate safety of ravulizumab SC and ravulizumab OBDS - To evaluate efficacy of ravulizumab SC - To assess performance of ravulizumab OBDS |
- Caratterizzare la farmacocinetica di ravulizumab SC - Caratterizzare la farmacodinamica di ravulizumab SC - Caratterizzare l'immunogenicità di ravulizumab SC - Valutare HRQoL e la soddisfazione al trattamento con ravulizumab SC - Valutare la sicurezza di ravulizumab SC e di ravulizumab OBDS - Valutare l'efficacia di ravulizumab SC - Valutare la performance di ravulizumab OBDS |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Age 1. Patients must be at least 18 years of age at the time of signing the informed consent.
Patient and Disease Characteristics 2. Treated with eculizumab according to the labeled dosing recommendation for PNH (900 mg every 14 days ± 2 days) for at least 6 months prior to study entry with no missed doses within 2 months prior to study entry and no more than 2 doses outside of the visit window. 3. Lactate dehydrogenase levels = 1.5 × ULN (upper limit of normal), according to central laboratory, at Screening. Sample must be obtained within 24 hours of or immediately prior to a scheduled eculizumab dose administration (ie, at trough eculizumab level). 4. Documented diagnosis of PNH confirmed by high-sensitivity flow cytometry evaluation (Borowitz, Craig et al. 2010). 5. Vaccinated against meningococcal infections within 3 years prior to, or at the time of, initiating study drug to reduce the risk of meningococcal infection (N meningitidis). |
Età 1. I pazienti devono avere minimo 18 anni al momento della firma del consenso informato.
Pazienti e caratteristiche della malattia 2. Trattati con eculizumab secondo il dosaggio previsto sull'etichetta per pazienti con PNH (900 mg ogni 14 giorni ± 2 giorni) per almeno 6 mesi prima dell'entrata nello studio e che non abbiano saltato alcuna dose entro i 2 mesi prima dell'inizio dello studio e che non abbiano ricevuto più di 2 dosial di fuori della finiestra delle visite. 3. Livelli di lattatodeidrogenasi = 1.5 × ULN (upper limit of normal), secondo il laboratorio centrale, allo screening. I campioni devono essere ottenuti entro 24 ore oppure immediatamente prima di un trattamento programmato con eculizumab (i.e. con il livello pià basso di eculizumab) 4. Diagnosi documentata di PNH confermata da citometria a flusso ad alta sensibilità (Borowitz, Craig et al. 2010). 5. Vaccinati contro infezione meningococcica entro 3 anni dall'inizio dello studio, oppure all'inizio dello studio, per ridurre il rischio di infezione meningococcica (N meningitidis). |
|
E.4 | Principal exclusion criteria |
Medical Conditions 1. More than 1 LDH value > 2 × ULN within the 6 months prior to study entry. 2. Major adverse vascular event (MAVE) in the 6 months prior to study entry. 3. Platelet count < 30,000/mm3 (30 × 109/L) at Screening. 4. Absolute neutrophil count < 500/µL (0.5 × 109/L) at Screening. 5. History of bone marrow transplantation. 6. History of N meningitidis infection. |
Condizione medica 1. Più di 1 valore di LDH > 2 × ULN entro 6 mesi dall'ingresso nello studio. 2. Evento vascolare avverso importante (MAVE) entro 6 mesi priam dell'ingresso nello studio. 3. Conta delle piastrine < 30,000/mm3 (30 × 109/L) allo screening 4. Conta assoluta dei neutrofili < 500/µL (0.5 × 109/L) allo screening 5. Anamnesi di trapianto di midollo 6. Anamnesi di infezione da N meningitidis |
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E.5 End points |
E.5.1 | Primary end point(s) |
Day 71 serum ravulizumab Ctrough |
Cthrough di ravulizumab nel siero al giorno 71 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
- PK Endpoint: Ctrough over time - PD Endpoint: Free serum C5 concentrations over time - Immunogenicity - HRQoL and Treatment Satisfaction Endpoints - Safety Endpoints - Efficacy Endpoints |
- Cthrough e PK nel tempo - PD: concentrazione diC5 nel siero nel tempo - Immunogenicità - HRQoL e soddisfazione al trattamento - Sicurezza - Efficacia |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Throughout the study |
Durante lo studio |
|
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 | Yes |
E.8.1.7.1 | Other trial design description |
I pazienti nel gruppo ravulizimab IV passeranno a ravulizumab SC 490 mg durante il periodo di estens |
Patients in the ravulizumab IV group will switch to 490 mg of ravulizumab SC in the extension period |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Stesso farmaco, forma farmaceutica differente. |
Same drug, different pharmaceutical form. |
|
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 46 |
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 |
Australia |
Brazil |
Canada |
Korea, Republic of |
Russian Federation |
Turkey |
United States |
Austria |
Belgium |
Czechia |
Finland |
France |
Germany |
Italy |
Netherlands |
Spain |
Sweden |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | No |
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
|
The end of the study is defined as the date of the last patient visit or safety follow up, whichever occurs later. |
La fine dello studio è definita come la data dell'ultima visita dell'ultimo paziente oppure del follow-up di sicurezza, a seconda di quale evento occorra prima. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |