E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with Post-polio syndrome |
Pacientes con síndrome de Post-polio |
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E.1.1.1 | Medical condition in easily understood language |
Therapy for subjects suffering post-poliomyelitis syndorme |
Terapia para sujetos que padecen el síndrome de post-poliomelitis |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10036239 |
E.1.2 | Term | Post polio syndrome |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10029205 |
E.1.2 | Term | Nervous system disorders |
E.1.2 | System Organ Class | 10029205 - Nervous system 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 safety and efficacy of Flebogamma 5% DIF in patients with post-polio syndrome |
Evaluar la eficacia y seguridad de Flebogamma 5% DIF en pacientes con el síndrome de post-polio |
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E.2.2 | Secondary objectives of the trial |
To evaluate clinical effect of Flebogamma 5%DIF in PPS subjects by: - assessing pain , as measured by VAS of pain, compared to that of placebo - evaluating health-related quality of life (HRQoL), as measured by SF-36 PCS, compared to that of placebo - endurance, as measured by 6MWD, compared to that of placebo. |
Evaluar el efecto clínico de Flebogamma 5% DIF en sujetos con PPS mediante: - evaluación del dolor, medido con la Escala Analógica del Dolor [VAS], comparado con el del placebo - evaluando la Calidad de Vida Relacionada con la Salud (HRQoL), medida con el Cuestionario de salud [SF-36], comparada con la de placebo -resistencia, medida con la Distancia Recorrida en 6 Minutos Caminando [6MWD], comparada con la de placebo |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Clinical trial subject inclusion criteria: 1. Male or female aged 18 to 75 years. 2. Subjects who understand and voluntarily signed and dated the Clinical Trial Written Informed Consent Form for his/her clinical trial participation. 3. Subjects with a body mass index (BMI) less than 35 kg/m2. 4. Subjects who meet the clinical criteria for diagnosis of PPS as set by the March-of-Dimes. 5. Subjects who are ambulatory or are able to walk with a cane or other aids. 6. Subjects who have two newly weakened muscle groups, and one of them in a lower extremity, as defined by medical history and having a MRC scale score of greater than three at the SV. 7. Female subjects of child-bearing potential must have a negative test for pregnancy (human chorionic gonadotropin [HCG]-based assay). 8. Female subjects of child-bearing potential and their sexual partners have agreed to practice contraception using a method of proven reliability (i.e., hormonal methods; barrier methods; intrauterine devices methods) to prevent a pregnancy during the course of the clinical trial. 9. Subjects must be willing to comply with all aspects of the clinical trial protocol, including blood sampling and long-term storage of extra samples for the entire duration of the study. 10. Subjects who are able to walk a 2MWD of at least 50 meters at the Screening Visit (SV) and EV/IV1. 11. Subjects who are able to walk a consistent baseline 2MWD, that is, the difference in 2MWD between the SV and EV/IV1 is not more than 10%. |
Criterios de inclusión del paciente en el ensayo clínico: 1.Hombre o mujer entre 18 y 75 años. 2.Sujetos que sean capaces de entender, firmar y fechar el Formulario de Información al Paciente y Consentimiento Informado del Ensayo Clínico para su participación en el ensayo clínico. 3.Sujetos con un índice de masa corporal (BMI) inferior a 35 kg/m2. 4.Sujetos que cumplan con los criterios clínicos de diagnóstico de PPS según lo establecido por la March-of-Dimes. 5.Sujetos ambulatorios o capaces de caminar con un bastón u otra ayuda. 6.Sujetos que tengan al menos dos grupos de músculos debilitados recientemente, y uno de ellos sea en una de las extremidades inferiores, tal como se define en la historia clínica y con una puntuación en la escala MRC superior a tres en la SV. 7.Los sujetos femeninos en edad fértil deben tener una prueba negativa de embarazo (gonadotropina coriónica humana [HCG]). 8.Sujetos femeninos en edad fértil y sus parejas sexuales que han acordado practicar la anticoncepción utilizando un método de probada fiabilidad (es decir, los métodos hormonales, métodos de barrera, métodos de dispositivos intrauterinos) para evitar un embarazo durante el transcurso del ensayo clínico. 9.Los sujetos deben estar dispuestos a cumplir con todos los aspectos del protocolo del ensayo clínico, incluyendo la extracción de sangre y el almacenamiento a largo plazo de muestras adicionales durante todo el estudio. 10.Sujetos que sean capaces de caminar al menos 50 metros en el 2MWD en la visita de selección (SV) y en la EV / IV1. 11. Sujetos que sean capaces de caminar un 2MWD en el inicio consistente, es decir, que la diferencia del 2MWD entre la SV y la EV / IV1 no sea más del 10%.
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E.4 | Principal exclusion criteria |
Clinical trial subject exclusion criteria: 1. Subjects who have received immune globulin treatment given by intravenous, subcutaneous or intramuscular route within the last 3 years. 2. Subjects who are not ambulatory (wheelchair-bound individuals). 3. Subjects with poor venous access. 4. Subjects with intractable pain requiring narcotics or other psychotropic drugs. 5. Subjects with a history of anaphylactic reactions or severe reactions to any blood-derived product. 6. Subjects with a history of intolerance to any component of the investigational products, such as sorbitol. 7. Subjects who are receiving corticosteroids, except for those who are taking inhaled corticosteroids for asthma. 8. Subjects with a documented diagnosis of hyperviscosity or hypercoagulable state or thrombotic complications to polyclonal IVIG therapy in the past. 9. Subjects with a history of recent (within the last year) myocardial infarction, stroke, or uncontrolled hypertension. 10. Subjects who suffer from congestive heart failure, embolism, or ECG changes indicative of unstable angina or atrial fibrillation. 11. Subjects with a history of chronic alcoholism or illicit drug abuse (addiction) in the preceding 12 months prior to the SV. 12. Subjects with active psychiatric illness that interferes with compliance or communication with health care personnel. 13. Subjects with depression with scores >30 as assessed by the CESD validated scale. 14. Females who are pregnant or are nursing an infant child. 15. Subjects with any medical condition which makes clinical trial participation unadvisable or which is likely to interfere with the evaluation of the study treatment and/or the satisfactory conduct of the clinical trial according to the Investigator?s judgment. 16. Subjects currently receiving, or have received within 3 months prior to the Screening Visit, any investigational medicinal product or device. 17. Subjects who are unlikely to adhere the protocol requirements, or are likely to be uncooperative, or unable to provide a storage serum/plasma sample prior to the first investigational drug infusion. 18. Subjects with a known selective IgA deficiency and serum antibodies anti-IgA. 19. Subjects with renal impairment (i.e., serum creatinine exceeds more than 1.5 time the upper limit of normal [ULN] for the expected normal range for the testing laboratory). 20. Subjects with AST or ALT levels exceeding more than 2.5 times the ULN for the expected normal range for the testing laboratory. 21. Subjects with hemoglobin levels <10 g/dL, platelets levels <100,000/mm3, white blood cells count <3.0 k/?L and ESR >50 mm/h or twice above normal. 22. Subjects with known seropositive to HCV, HIV-1 and/or HIV-2. 23. Subjects with a history of intolerance to fructose |
Criterios de exclusión del paciente en el ensayo clínico: 1.Sujetos que han recibido tratamiento con inmunoglobulina administrada por vía intravenosa, subcutánea o intramuscular en los últimos 3 años. 2.Sujetos que no sean ambulatorios (pacientes en silla de ruedas). 3.Sujetos con acceso venoso pobre. 4.Sujetos con dolor que requiera narcóticos u otras drogas psicotrópicas. 5.Sujetos con antecedentes de reacciones anafilácticas o reacciones graves a cualquier producto derivado de la sangre. 6.Sujetos con una historia de intolerancia a cualquier componente de los productos en investigación, tales como sorbitol. 7.Sujetos que estén recibiendo corticosteroides, a excepción de aquellos que están tomando corticosteroides inhalados para el asma. 8.Sujetos con un diagnóstico documentado de hiperviscosidad o estado de hipercoagulación o complicaciones trombóticas a la terapia con IVIG policlonal en el pasado. 9.Sujetos con un historial reciente (en el último año) de infarto de miocardio, accidente cerebrovascular o hipertensión no controlada. 10.Sujetos con insuficiencia cardíaca congestiva, embolia, o cambios en el ECG indicativos de angina inestable o fibrilación auricular. 11.Sujetos con antecedentes de alcoholismo crónico o de abuso de drogas ilícitas (adicción) en los 12 meses anteriores a la SV. 12.Sujetos con enfermedad psiquiátrica activa que interfiere con el cumplimiento o la comunicación con el personal de atención de salud. 13.Sujetos con depresión cuya puntuación en la escala validada CESD > 30. 14.Mujeres que están embarazadas o que están lactando a un recién nacido. 15.Sujetos con alguna condición médica que desaconseje la participación en el ensayo clínico o que sea probable que interfiera en la evaluación del tratamiento del estudio y / o la realización satisfactoria del ensayo clínico a juicio del investigador. 16.Sujetos que actualmente reciben, o han recibido en los 3 meses previos a la visita de selección, cualquier medicación en investigación o artefacto. 17. Sujetos que no sea probable que se adhieran a los requisitos del protocolo, o sean susceptibles de ser poco cooperativos, o incapaces de proporcionar una muestra de suero / plasma de almacenamiento antes de la primera infusión del fármaco. 18.Sujetos con deficiencia selectiva de IgA conocida y anticuerpos séricos anti-IgA. 19.Sujetos con insuficiencia renal (es decir, si la creatinina sérica supera más de 1,5 veces el límite superior normal [ULN] del rango normal de laboratorio). 20.Sujetos con niveles de AST o ALT superiores a más de 2,5 veces el valor máximo de normalidad del rango normal de laboratorio. 21.Sujetos con niveles de hemoglobina <10 g / dl, niveles de plaquetas <100.000 / mm3, recuento de glóbulos blancos <3,0 k / l y VSG> 50 mm / h o dos veces por encima del valor normal. 22.Sujetos seropositivos conocidos a HCV, HIV-1 y / o HIV-2. 23.Sujetos con antecedentes de intolerancia a la fructosa.
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E.5 End points |
E.5.1 | Primary end point(s) |
To test whether monthly infusions (every four weeks) of intravenous Flebogamma® 5% DIF in a 1 year treatment period in PPS subjects are superior to placebo by assessing physical performance, as measured by 2MWD (2-minutes walk distance) For Stage 1, to select the optimal dose of IVIG as compared to the placebo. For Stage 2, to establish superiority of the selected dose of IVIG as compared to placebo by combining both Stage 1 and Stage 2 data. |
Evaluar si las infusiones mensuales (cada cuatro semanas) de Flebogamma® 5% DIF intravenosa en un periodo de 1 año de tratamiento en pacientes con PPS son superiores a placebo a través de la evaluación del rendimiento físico, calculado con el 2MWD. En la Etapa 1, seleccionar la dosis óptima de IVIG comparada con el placebo. En la Etapa 2, establecer la superioridad de la dosis seleccionada de IVIG comparada con el placebo, combinando los datos de la Etapa 1 y la Etapa 2.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1 year treatment |
1 año de tratamiento |
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E.5.2 | Secondary end point(s) |
Efficacy endpoints: - Pain (Visual Analogue Scale [VAS] of pain) from baseline to the end of the treatment period. - HRQoL (Medical Outcomes Study 36-Item Short Form Health Survey [SF-36] Physical Component Summary [PCS]) from baseline to the end of the treatment period. - Endurance (Six Minutes Walk Distance [6MWD]) from baseline to the end of the treatment period.
Safety endpoints will include Adverse Events (AEs), vital signs during infusions, physical assessments and blood tests for clinical safety. |
Variables de eficacia: -Dolor (Escala Analógica Visual del Dolor [VAS]) desde el inicio hasta el final del período de tratamiento. -HRQoL (Cuestionario de salud [SF-36] como instrumento para evaluar la Calidad de Vida Relacionada con la Salud (HRQoL)) desde el inicio hasta el final del período de tratamiento. -Resistencia (Distancia Recorrida en 6 Minutos Caminando [6MWD]) desde el inicio hasta el final del período de tratamiento.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
One year treatment. And for the one year treatments and a half year without treatment (to assess the sustainability effect). |
Un año de tratamiento Un año de tratamiento y medio año sin (recibir) tratamiento para evaluar el efecto sostenido (del medicamento en investigación).
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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 | No |
E.6.7 | Pharmacodynamic | No |
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) | 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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 |
It is a study trial with two stages design |
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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 | 3 |
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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
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 |
Canada |
Denmark |
Germany |
Italy |
Netherlands |
Poland |
Romania |
Spain |
Sweden |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
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 | 4 |
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 |