E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
APDS/PASLI (Activated phosphoinositide 3-kinase delta syndrome/p110d-activating mutation causing senescent T cells, lymphadenopathy and immunodeficiency) |
APDS/PASLI - Sindrome da attivazione di PIK3-delta/immunodeficienza, linfadenopatia e cellule T senescenti da mutazione attivante p110-delta |
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E.1.1.1 | Medical condition in easily understood language |
Gain of function genetic mutation in the PI3Kdelta gene causing immunodeficiency |
Sindrome da attivazione di PIK3-delta/immunodeficienza, linfadenopatia e cellule T senescenti da mutazione attivante p110-delta |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10064859 |
E.1.2 | Term | Primary immunodeficiency syndrome |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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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 the long term safety and tolerability of CDZ173 in patients with APDS/PASLI. |
Valutare sicurezza e tollerabilità di CDZ173 a lungo termine su pazienti con APDS/PASLI. |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the long term efficacy of CDZ173 to modify healthrelated quality of life in patients with APDS/PASLI. - To evaluate the long term efficacy of CDZ173 by means of biomarkers reflecting the efficacy of CDZ173 to reduce systemic inflammatory components of the disease in patients with APDS/PASLI. - To characterize the pharmacokinetics (trough concentrations) of CDZ173 in patients with APDS/PASLI. - To evaluate the pharmacokinetics and relative bioavailability of CDZ173 film-coated tablets compared to CDZ173 hard-gelatin capsules. |
- Valutare l’efficacia a lungo termine di CDZ173 nel modificare la qualità della vita in relazione alla salute nei pazienti con APDS/PASLI. - Valutare l’efficacia a lungo termine di CDZ173 attraverso la valutazione di biomarcatori che riflettono l’efficacia di CDZ173 nel ridurre le componenti dell’infiammazione sistemica su pazienti con APDS/PASLI. - Caratterizzare la farmacocinetica (livelli pre dose) di CDZ173 su pazienti con APDS/PASLI. - Valutare la farmacocinetica e la biodisponibilità relativa del CDZ173 in forma di compresse rivestite da film rispetto al CDZ173 in capsule di gelatina dura |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patients must have participated in study CCDZ173X2201 or were treated previously with PI3Kd inhibitors other than CDZ173. - Patients who are deemed by the Investigator to benefit from PI3Kd inhibitor therapy. - Patients or their legal representatives (for patients under the age of 18 years) must be able to communicate well with the Investigator, to understand and comply with the requirements of the study. - Documented APDS/PASLI-associated genetic PI3K delta mutation. Patients with mutations in either PIK3CD or PIK3R1 can be included. |
- I pazienti devono aver partecipato allo studio CCDZ173X2201 o aver ricevuto precedente terapia con altri inibitori PI3K-delta, diversi dal CDZ173. - Pazienti che secondo lo sperimentatore possono trarre beneficio dalla terapia con inibitori del PI3K-delta. - Pazienti o loro rappresentanti legali (per pazienti con meno di 18 anni) devono essere in grado di comunicare con lo sperimentatore in modo da capire e rispettare i requisiti dello studio. - Diagnosi documentata di APDS/PASLI associata alla mutazione genetica PI3K delta. Possono essere inclusi pazienti con le mutazioniPIK3CD o PIK3R1. |
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E.4 | Principal exclusion criteria |
- Patients who withdrew consent from the study CCDZ173X2201. - Use of other investigational drugs, except CDZ173, within 5 half-lives of enrollment, or within 30 days, whichever is longer. - Previous or concurrent use of immunosuppressive medication - Administration of any live vaccines (including any attenuated live vaccines) starting from 6 weeks before study entry, during the study and up to 7 days after the last dose of CDZ173 should be excluded. - Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation. - Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 2 days after last dose ofstudy medication. - Uncontrolled chronic or recurrent infectious disease (with the exception of those that are considered to be characteristic of APDS/PASLI). |
- Pazienti che hanno ritirato il consenso dello studio CCDZ173X2201. - Uso di farmaci sperimentali, eccetto CDZ173, entro il periodo definito come 5 volte il tempo di dimezzamento dall’arruolamento o nei 30 giornì precedenti l’arruolamento, qualunque delle due situazioni si verifichi per prima. - Uso precedente o concomitante di farmaci immunosoppressori. - Dovrebbero essere esclusi pazienti che hanno assunto qualsiasi vaccino vivo (compresi vaccini vivi attenuati) nelle 6 settimane precedenti l’arruolamento. Durante lo studio e fino a 7 giorni dopo l’ultima dose di CDZ173 è vietata la somministrazione di qualsiasi vaccino vivo. - Donne in gravidanza o allattamento, con la gravidanza definita come lo stato di una donna dopo il concepimento e fino al termine della gestazione, confermato da un test di laboratorio positivo per hCG. - Donne potenzialmente fertili, definite come tutte le donne fisiologicamente in grado di iniziare una gravidanza, a meno che non utilizzino metodi contraccettivi di efficacia elevata (ad esclusione di contraccettivi ormonali orali, cerotti, impianti sottocutanei o iniettabili) durante la somministrazione del trattamento in studio e per i 2 giorni successivi all'interruzione del trattamento. - Pazienti con infezioni croniche o ricorrenti non controllate ( con eccezione di quelle che sono considerate essere caratteristiche della patologia APDS/PASLI). |
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E.5 End points |
E.5.1 | Primary end point(s) |
All safety parameters (including AEs, physical exam, vital signs, ECG, safety laboratory (hematology, blood chemistry, urinalysis)) |
Tutti i parametri di sicurezza (AEs, visita medica, segni vitali, ECG, esami di sicurezza di laboratorio (ematologia, chimica clinica, ecc). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
5 years and 3 months |
5 anni e 3 mesi |
|
E.5.2 | Secondary end point(s) |
- SF-36 (Short Form 36) Survey and WPAI-CIQ (Work Productivity Activity Impairment plus Classroom Impairment Questionnaire), Visual analogue scales for Physician's Global Assessment (PGA) and Patient's Global Assessment (PtGA), patient narratives by Investigator - High sensitivity C-reactive protein (CRP), lactate dehydrogenase (LDH), frequencies of infections and other disease complications. - Steady-state trough concentration of CDZ173. - PK parameters (including but not limited to AUC0-12,ss and Cmax,ss) |
- SF-36 (Short Form 36) Survey e WPAI-CIQ (Work Productivity Activity Impairment plus Classroom Impairment Questionnaire), scale visive analogiche per Physician's Global Assessment (PGA) e Patient's Global Assessment (PtGA), racconti dei pazienti per Investigatore - Proteina C reattiva (CRP) ad alta sensibilità, lattato deidrogenasi (LDH), frequenze di infezioni e altre complicanze della malattia. - Concentrazione minima allo stato stazionario di CDZ173. - Parametri PK (inclusi ma non limitati a AUC0-12, ss e Cmax, ss) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
5 years and 3 months |
5 anni e 3 mesi |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability |
Tollerabilità |
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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) | 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 | No |
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
| 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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
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 |
Belarus |
Russian Federation |
United States |
Ireland |
Italy |
Netherlands |
United Kingdom |
Czechia |
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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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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 | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 29 |