E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HIV-infected patients with Progressive Multifocal Leukoencephalopathy |
Pacientes infectados con VIH que han desarrollado leucoencefalopatía multifocal progresiva |
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E.1.1.1 | Medical condition in easily understood language |
HIV-infected patients with Progressive Multifocal Leukoencephalopathy |
Pacientes infectados con VIH que han desarrollado leucoencefalopatía multifocal progresiva |
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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 | 15.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10036807 |
E.1.2 | Term | Progressive multifocal leukoencephalopathy |
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. |
El objetivo principal de este estudio es evaluar la eficacia del CYT107 en la eliminación del virus John Cunningham (JC) del líquido cefalorraquídeo (LCR) |
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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 |
Los objetivos secundarios son: ? evaluar la seguridad clínica del CYT107 ? evaluar el efecto en la supervivencia del paciente ? medir el efecto en el estado clínico y neurológico ? evaluar la actividad biológica de la CYT107: o en la cinética del cambio de carga del virus JC en el líquido cefalorraquídeo o en los parámetros principales de la reconstitución inmune o en la respuesta específica de los linfocitos T frente al virus JC |
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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, established by criteria defined in protocol 4. Patients have to be on effective cART after PML diagnosis, for at least 4 weeks. 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. Edad ?18 años. 2. Infección por VIH-1. 3. Resultados neurológicos compatibles con el desarrollo de la leucoencefalopatía multifocal progresiva activa (LMP), según los criterios establecidos en el protocolo. 4. Después de haber sido diagnosticada la leucoencefalopatía multifocal progresiva, los pacientes tienen que llevar como mínimo 4 semanas en terapia antirretroviral efectiva combinada. 5. Carga en sangre de ARN del virus VIH <1.000 copias/mL. 6. Nivel funcional de Karnofsky, puntuación ? 30. 7. Paciente con seguro médico o ayuda estatal. 8. Capacidad del paciente (o del representante legal en caso de deficiencia del paciente para tomar decisiones) de entender y firmar el consentimiento informado. |
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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. 4. Prior treatment with interleukin-7. 5. Hepatitis B surface antigen (HBsAg) positive. 6. ALT and/or AST > 5 x ULN. 7. Use of another investigational or interventional treatment within the last 3 months prior to study entry. 8. Any current malignancy except Kaposi Sarcoma that does not require chemotherapy. 9. Current opportunistic CNS 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 enrollment. |
1. Embarazo y lactancia. 2. Rechazo y/o imposibilidad de utilizar una contracepción independientemente del sexo del paciente. 3. Síndrome inflamatorio de reconstitución inmunitaria asociado a la leucoencefalopatía multifocal progresiva (LMP-SIRI) documentado por resonancia magnética. 4. Tratamiento previo con interleucina-7. 5. Antígeno de superfície de Hepatitis B (HbsAg) positivo. 6. Alanina transaminasa (ALT) y/o Aspartato transaminasa (ASAT) > 5 x como límite superior. 7. Uso de otros tratamientos de investigación o cualquier intervención realizada durante los 3 meses anteriores a la incorporación al ensayo. 8. Cualquier afección maligna, excepto el sarcoma de Kaposi, que no requiera quimioterapia. 9. Presencia de otra infección oportunista del sistema nervioso central (SNC). 10. Tuberculosis activa. 11. Presencia de otra enfermedad grave (enfermedad autoinmune, enfermedad mental grave) u otra condición que, en opinión del investigador, haría que el sujeto no fuese apto para su reclutamiento. |
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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. |
El parámetro de eficacia principal será el porcentaje de pacientes que eliminen el virus JC del LCR en 3 meses. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary endpoint will be assessed at 3 months. |
El parámetro de eficacia principal será evaluado despues de 3 meses. |
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E.5.2 | Secondary end point(s) |
The secondary endpoints are: ? Kinetics of the JC viral load changes ? ?Survival? curves for time to JCV viral clearance in CSF ? MRI lesions changes ? Percentage change in neurological scores ? Change in Karnofsky Performance Status; ? MRS scores ? Proportion of patients with a MRS score < 3 ? Changes in CD4+ and CD8+ T-cell subsets ? Changes of specific T-cell responses, proliferation indices, JCV-specific T-cell responses ? Survival rate |
Los parámetros secundarios serán los siguientes: ? Se analizará la cinética del cambio de carga del virus JC en el líquido cefalorraquídeo ? El tiempo necesario para eliminar el virus en el liquido cefalorraquideo ? Cambios en lesiones IRM ? Evaluación neurológica ? Cambios en los resultados MRS ? Cambios en los contajes totales de células CD4, CD8 ? Cambios en las respuestas especificas de las celulas T, indices de proliferaction y respuestas especificas de las celulas T contra el JCV ? Estado de sobreviviencia |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Timepoints of evaluation of secondary endpoints are as follows: ? Kinetics of the JCV viral load changes from D0 to M3 ? Kinetics of the JCV viral load changes from D0 to M12 ? ?Survival? curves for time to JCV viral clearance in CSF ? Percentage change in neurological scores between baseline and M12 ? Change in Karnofsky Performance Status between D0 and M12; ? MRS scores at M12 ? Survival rate at M12 |
? Cinética del cambio de carga del virus JC en el líquido cefalorraquídeo del D0 al M3 y del D0 al M12 ? El tiempo necesario para eliminar el virus en el liquido cefalorraquideo ? Evaluación neurológica desde el inicio hasta el M12 ? Cambios en los resultados MRS desde el inicio hasta el M12 ? Estado de sobreviviencia en el M12 |
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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 | 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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 |
European Union |
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
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Last patient last visit date. |
Ultima visita del ultimo paciente. |
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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 | 6 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |