E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with acid sphingomyelinase deficiency (Niemann-Pick Type B disease) |
Pazienti con deficit di sfingomielinasi acida (malattia di Niemann-Pick di Tipo B) |
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E.1.1.1 | Medical condition in easily understood language |
Patients with Niemann-Pick Type B disease |
Pazienti con malattia di Niemann- Pick di Tipo B |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
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 | 10041515 |
E.1.2 | Term | Sphingomyelin lipidosis |
E.1.2 | System Organ Class | 100000004850 |
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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 |
The primary objective of this study is to obtain data regarding the safety of olipudase alfa in patients with acid sphingomyelinase deficiency (ASMD) who are exposed to long term treatment with olipudase alfa
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L’obiettivo primario dello studio prevede l’acquisizione di dati relativi alla sicurezza di olipudase alfa in pazienti con deficit della sfingomielinasi acida (acid sphingomyelinase deficiency, ASMD) sottoposti a trattamento a lungo termine con olipudase alfa. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to obtain data regarding the efficacy of olipudase alfa and to characterize olipudase alfa pharmacodynamics (PD) and pharmacokinetics (PK) following long-term administration |
Gli obiettivi secondari di questo studio prevedono l’acquisizione di dati relativi all’efficacia di olipudase alfa e la caratterizzazione farmacodinamica (pharmacodynamics, PD) e farmacocinetica (pharmacokinetics, PK) di olipudase alfa a seguito della somministrazione a lungo termine. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
The patient completed the treatment period of a previous study of olipudase alfa with an acceptable safety profile in the opinion of the investigator and sponsor
The patient and/or the patient's parent(s)/legal guardian(s) is willing and able to provide signed written informed consent.
The patient who is female and of childbearing potential must have a negative urine pregnancy test for beta human chorionic gonadotropin (β HCG).
Female patients of childbearing potential and sexually mature male patients must be willing to practice true abstinence in line with their preferred and usual lifestyle or use 2 acceptable effective methods of contraception up to 15 days following their last dose of study drug
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Il paziente ha completato il periodo del trattamento di un precedente studio su olipudase alfa con un profilo di sicurezza accettabile secondo il parere dello sperimentatore e dello sponsor.
• Il paziente e/o il/i genitore/i o il/i tutore/i legale/i del paziente devono essere disposti e in grado di fornire il consenso informato firmato.
• Le donne potenzialmente fertili devono presentare un test di gravidanza sulle urine per la gonadotropina corionica umana beta (β-HCG) con esito negativo.
• Le donne potenzialmente fertili e gli uomini sessualmente maturi devono essere disposti a praticare un’effettiva astinenza in linea con le proprie preferenze e il proprio stile di vita oppure utilizzare 2 metodi contraccettivi efficaci accettabili fino a 15 giorni dopo l’ultima dose del farmaco dello studio.
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E.4 | Principal exclusion criteria |
The patient has any new condition or worsening of an existing condition which in the opinion of the investigator would make the patient unsuitable for enrollment, or could interfere with the patient participating in or completing the study.
The patient, in the opinion of the investigator, is unable to adhere to the requirements of the study.
The patient is unwilling or unable to abstain from the use of alcohol for 1 day prior to and 3 days after each olipudase alfa infusion for the duration of the treatment period.
The patient is unwilling or unable to avoid, for 10 days before and 3 days after liver biopsies, medications or herbal supplements that are potentially hepatotoxic (eg, 3 hydroxy 3 methylglutaryl coenzyme A reductase inhibitors, erythromycin, valproic acid, antidepressants, kava, echinacea) or may cause or prolong bleeding (eg, anticoagulants, ibuprofen, aspirin, garlic supplements, ginkgo, ginseng).
The patient requires medication(s) that may decrease olipudase alfa activity (eg, fluoxetine, chlorpromazine; tricyclic antidepressants [eg, imipramine, desipramine]).
The patient has an alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >250 IU/L or total bilirubin >1.5 mg/dL
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• Il paziente presenta un nuovo disturbo o il peggioramento del quadro clinico esistente che, a parere dello sperimentatore, potrebbe rendere il paziente non idoneo all’arruolamento oppure potrebbe interferire con la sua partecipazione allo studio o con la sua capacità di portarlo a termine.
• Il paziente, a parere dello sperimentatore, non è in grado di aderire ai requisiti dello studio.
• Il paziente non è disposto o in grado di astenersi dall’uso di alcolici nel giorno precedente e nei 3 giorni successivi a ciascuna infusione di olipudase alfa per tutta la durata del periodo del trattamento.
• Il paziente non è disposto o in grado di evitare, nei 10 giorni precedenti e nei 3 giorni successivi le biopsie epatiche, l’uso di farmaci o integratori a base di erbe potenzialmente epatotossici (es. inibitori della 3-idrossi-3-metilglutaril coenzima A, eritromicina, acido valproico, antidepressivi, kava, echinacea) oppure che possono causare o prolungare il sanguinamento (es. anticoagulanti, ibuprofene, aspirina, integratori a base di aglio, ginkgo, ginseng).
• Il paziente necessita di farmaco/i che può/possono ridurre l’attività di olipudase alfa (es. fluoxetina, clorpromazina, antidepressivi triciclici [es. imipramina, desipramina]).
• Il paziente presenta valori di alanina aminotransferasi o aspartato aminotransferasi >250 IU/L o di bilirubina totale >1,5 mg/dL.
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E.5 End points |
E.5.1 | Primary end point(s) |
- Adverse events//treatment-emergent adverse events, including infusion-associated reactions.
Physical examinations including neurologic examinations.
Vital signs, echocardiograms and electrocardiograms.
Clinical laboratory tests.
Safety biomarkers.
- Liver biopsy (patients previously enrolled in DFI13412).
Liver ultrasound/Doppler (patients previously enroiled in DFI13803).
- Immune response assessments |
• Eventi avversi/eventi avversi emergenti dal trattamento, incluse le reazioni associate all’infusione.
• Esami obiettivi, inclusi esami neurologici.
• Misurazione dei segni vitali, Ecocardiografia e Elettrocardiogrammi
• Analisi cliniche di laboratorio.
• Biomarcatori di sicurezza.
• Biopsia epatica (solo pazienti che hanno precedentemente partecipato allo studio DFI13412).
• Ecografia epatica con Doppler (solo pazienti che hanno precedentemente partecipato allo studio DFI13803).
• Valutazioni della risposta immunitaria.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline to 5 years |
Dal basale a 5 anni |
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E.5.2 | Secondary end point(s) |
- Abdominal magnetic resonance imaging (MRI) to evaluate improvements in spleen and liver volume
- Pulmonary Imaging
- Pulmonary function test
- Hematology (hemoglobin and platelet count)
- Lipid profile
- Health outcome questionnaires
- Hand X ray for bone age and bone maturation (pediatric patients)
- Tanner staging (pediatric patients)
- Linear patient growth by height Z -score (pediatric patients) |
• Risonanza magnetica per immagini (RMI) addominale per valutare i miglioramenti nel volume di milza e fegato.
• Imaging polmonare
• Test di funzionalità polmonare
• Ematologia (emoglobina e conta piastrinica)
• Profilo lipidico
• Questionari sullo stato di salute
• Radiografia della mano per la valutazione dell’età ossea e della maturazione ossea (pazienti pediatrici)
• Stadiazione di Tanner (pazienti pediatrici)
• Crescita lineare dei pazienti mediante Z-score per l’altezza (pazienti pediatrici).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Abdominal magnetic resonance imaging (MRI) to evaluate improvements in spleen and liver volume - Baseline to 5 years
- Pulmonary Imaging - Baseline to 5 years
- Pulmonary function test - Baseline to 5 years
- Hematology (hemoglobin and platelet count) - Baseline to 5 years
- Lipid profile - Baseline to 5 years
- Health outcome questionnaires - Baseline to 5 years
- Hand X ray for bone age and bone maturation (pediatric patients) - Baseline to 5 years
- Tanner staging (pediatric patients) - Baseline to 5 years
- Linear patient growth by height Z -score (pediatric patients) - Baseline to 5 year |
Dal basale a 5 anni |
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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 | No |
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 | Yes |
E.6.11 | Pharmacogenomic | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
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 |
Brazil |
France |
Germany |
Italy |
United Kingdom |
United States |
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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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Last visit of the last subject |
ULTIMA VISITA ULTIMO PAZIENTE |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |