E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HIV-infected patients with Progressive Multifocal Leukoencephalopathy |
Pazienti con infezione da HIV affetti da leucoencefalopatia multifocale progressiva |
|
E.1.1.1 | Medical condition in easily understood language |
HIV-infected patients with Progressive Multifocal Leukoencephalopathy |
Pazienti con infezione da HIV affetti da leucoencefalopatia multifocale progressiva |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10021881 |
E.1.2 | Term | Infections and infestations |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 main objective of this study is to assess CYT107 efficacy on JCV clearance from cerebrospinal fluid. |
Valutare l'efficacia di CYT107 sulla eliminazione del JCV (virus John Cunningham) dal liquido cerebrospinale (LCS) |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are: o to assess the clinical safety of CYT107 o to assess the effect on patient survival o to measure the effect on neurological and clinical status o to assess the biological activity of CYT107: - on the kinetics of JCV reduction in CSF - on the main parameters of the immune reconstitution - on the specific T-cell response against the JC virus |
· valutare la sicurezza clinica di CYT107 · valutare l'effetto sulla sopravvivenza del paziente · misurare l'effetto sullo stato neurologico e clinico · valutare l'attività biologica di CYT107: o sulla cinetica delle variazioni della carica virale JCV nell'LCS o sui principali parametri della ricostituzione immunitaria o sulla risposta delle cellule T specifiche contro il JCV |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age ≥18 years. 2. HIV-1 infection. 3. Neurological findings compatible with the development of active PML (Progressive Multifocal Leukoencephalopathy), established by the following criteria: a) Occurrence of new symptoms or worsening of pre-existing symptoms b) Detection of JCV DNA in CSF by qualitative PCR (Polymerase Chain Reaction) c) MRI (Magnetic Resonance Imaging) documented focal cerebral lesions in relation with symptoms d) No other likely cause according to investigator opinion 4. Patients have to be on effective cART after PML diagnosis for at least 4 weeks Note: effective cART is defined as a combination of marketed ARV (anti-retroviral) treatments according to national recommendations. 5. HIV RNA load in blood <1000 copies/mL. 6. Karnofsky Performance-Status, score ≥ 30. 7. Patient with medical insurance or government support. 8. Ability of the patient (or a legal representative if decision making capacity is impaired) to understand and sign informed consent. |
1. Età ≥ 18 anni. 2. Infezione da HIV-1. 3. Risultanze neurologiche compatibili con lo sviluppo di PML (leucoencefalopatia multifocale progressiva) attiva, stabilite in base ai seguenti criteri: a) Comparsa di nuovi sintomi o peggioramento di sintomi preesistenti b) Rilevazione del DNA di JCV nell'LCS mediante PCR (reazione a catena della polimerasi) qualitativa c) Lesioni cerebrali focali documentate tramite risonanza magnetica (RMN) in relazione con i sintomi d) Nessun altra causa probabile secondo lo sperimentatore 4. I pazienti devono essere in trattamento efficace con cART dopo la diagnosi della PML da almeno 4 settimane Nota: il trattamento efficace con cART è definito come una combinazione di trattamenti antiretrovirali (ARV) commercializzati in conformità alle raccomandazioni nazionali. 5. Carica virale di HIV-RNA nel sangue <1000 copie/mL. 6. Scala di Karnofsky, punteggio ≥ 30. 7. Paziente in possesso di assicurazione sanitaria o che beneficia dell'assistenza sanitaria pubblica. 8. Abilità del paziente (o del legale rappresentante se il paziente è incapace di decidere) di capire e firmare un modulo di consenso informato. |
|
E.4 | Principal exclusion criteria |
1. Pregnancy or breast feeding.
2. Refusal or inability to practice contraception regardless of the gender of the patient.
3. MRI documented PML-IRIS (Immune Reconstitution Inflammatory Syndrome)
4. Prior treatment with interleukin-7.
5. Hepatitis B surface Antigen (HbsAg) positive
6. ALT and/or AST > 5 x ULN.
7. Use of other investigational or any interventional treatments, within the last 3
months prior to study entry.
8. Any current malignancy except Kaposi Sarcoma that does not require
chemotherapy.
9. Other current opportunistic CNS (Central Nervous System) infection.
10. Active tuberculosis.
11. Other current severe illness or other conditions (such as autoimmune disease,
severe mental illness) that, in the opinion of the investigator, would make the
subject unsuitable for enrolment. |
1. Gravidanza o allattamento. 2. Rifiuto on inabilità a praticare la contraccezione indipendentemente dal genere del paziente 3. PML con insorgenza di IRIS (sindrome infiammatoria da ricostituzione immunitaria) documentata mediante RMN. 4. Trattamento precedente con interleuchina-7. 5. Antigene di superficie dell’epatite B (HbsAg) positivo. 6. ALT e/o ASAT > 5 x ULN. 7. Uso di altri trattamenti in fase di sperimentazione o interventistici, nei 3 mesi precedenti l'inclusione nello studio. 8. Qualsiasi tumore maligno ad eccezione del sarcoma di Kaposi che non necessita chemioterapia. 9. Altra infezione opportunistica del sistema nervoso centrale in corso. 10. Tubercolosi attiva. 11. Altra malattia grave in corso o altre patologie (quali malattia autoimmune, malattia mentale grave) che, secondo lo sperimentatore, renderebbero il soggetto non idoneo all'arruolamento. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is defined as the clearance of the JCV from the CSF at M3. |
L'endpoint primario di efficacia sarà la percentuale di pazienti con eliminazione del JCV dopo 3 mesi. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary endpoint will be assessed at 3 months. |
3 mesi. |
|
E.5.2 | Secondary end point(s) |
• Biological activity: o kinetics of JCV change in CSF will be analysed using both: the individual regression slope of CSF JCV load over the first three months and beyond a time to event approach o changes of the CD3, CD4, CD8 cell counts o changes of specific T-cell response against the JCV • Clinical activity: o overall survival at M12 o clinical status improvement of the patient throughout the study period o residual neurological sequelae at M12 |
• Attività biologica: o la cinetica della variazione del JCV nell'LCS sarà analizzata a mezzo di: pendenza della retta di regressione individuale della carica virale JCV nell'LCS nei primi tre mesi ed oltre un approccio ''time-to-event'' o variazioni della conta delle cellule CD3, CD4 e CD8 o variazioni della risposta delle cellule T specifiche contro il JCV • Attività clinica: o sopravvivenza globale al mese 12 o miglioramento dello stato clinico del paziente durante il periodo dello studio o sequele neurologiche residue al mese 12 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
D0, D7, D14, D21, D28, M2, M3, M6, M12 |
G0, G7, G14, G21, G28, M2, M3, M6, M12 |
|
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 | No |
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) | 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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
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 |
Switzerland |
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
|
|
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 |