E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic inflammatory demyelinating polyradiculoneuropathy |
polirradiculoneuropatía desmielinizante inflamatoria crónica |
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E.1.1.1 | Medical condition in easily understood language |
Chronic Inflammatory Demyelinating Polyneuropathy is a rare disorder of the peripheral nerves (nerves outside the central nervous system) caused by damage to the covering of the nerves called myelin |
La polineuropatía desmielinizante inflamatoria crónica es un trastorno poco frecuente de los nervios periféricos causada por el daño en la cubierta de los nervios llamados mielina |
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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 | 19.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10057645 |
E.1.2 | Term | Chronic inflammatory demyelinating polyradiculoneuropathy |
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 long-term safety, tolerability, and immunogenicity of HYQVIA/HyQvia. |
Evaluar la seguridad, la tolerabilidad y la inmunogenicidad a largo plazo de HYQVIA/HyQvia |
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E.2.2 | Secondary objectives of the trial |
To assess the long-term effect of HYQVIA/HyQvia on clinical outcome measures, including prevention of relapse, change in functional ability, hand grip strength, and muscle strength. To assess the long-term effect of HYQVIA/HyQvia on quality of life, health utility, health resource utilization (HRU), treatment satisfaction, treatment preference, and subject global impression of change. To explore further the pharmacokinetics of HYQVIA/HyQvia in CIDP subjects. |
Evaluar el efecto a largo plazo de HYQVIA/HyQvia sobre los criterios de valoración clínicos, como la prevención de recaídas, el cambio en la capacidad funcional, la fuerza de prensión manual y la fuerza muscular. Evaluar el efecto a largo plazo de HYQVIA/HyQvia en la calidad de vida, la utilidad sanitaria, la utilización de recursos sanitarios (URS), la satisfacción con el tratamiento, la preferencia de tratamiento y la impresión global del cambio por parte del paciente. Seguir estudiando la farmacocinética de HYQVIA/HyQvia en sujetos con PDIC. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Has completed Epoch 1 of Study 161403 or Study 161601 without CIDP worsening. If female of childbearing potential, the subject must have a negative pregnancy test at baseline and agree to employ adequate birth control measures (e.g. birth control pills/patches,intrauterine device (IUD), or diaphragm or condom [for male partner] with spermicidal jelly or foam) throughout the course of the study. |
Hayan terminado la época 1 del estudio 161403 sin que haya empeorado su PDIC. Si la participante es una mujer fértil, deberá obtener un resultado negativo en la prueba de embarazo que se realice durante la selección, y deberá aceptar el uso de métodos anticonceptivos adecuados (p. ej., pastillas o parches anticonceptivos, dispositivo intrauterino [DIU] o diafragma, o bien preservativo [para la pareja del sexo masculino] con gelatina o espuma espermicida) durante el transcurso del estudio. |
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E.4 | Principal exclusion criteria |
Subject has a serious medical condition such that in the opinion of the investigator the subject’s safety or medical care would be impacted by participation in this Extension Study. New medical condition that developed during participation in Study 161403 or Study 161601 that in the judgment of the investigator could increase risk to the subject or interfere with the evaluation of investigational medicinal product and/or conduct of the study. Subject is scheduled to participate in another, non-Baxalta clinical study involving an IP or investigational device during the course of this study. The subject is nursing or intends to begin nursing during the course of the study. Subject has participated in another clinical study involving an IP or investigational device within 30 days prior to enrollment, or is scheduled to participate in another clinical study (with the exception of Study 161403 or 161601) involving an IP or investigational device during the course of this study. The subject is a family member or employee of the investigator. |
El sujeto sufre una enfermedad grave tal que, en opinión del investigador, afectaría a la seguridad o a la atención médica del sujeto si participara en este estudio de extensión. Enfermedad nueva aparecida durante la participación en el estudio 161403 o 161601 que, a juicio del investigador, podría aumentar el riesgo para el sujeto o interferir en la evaluación del producto en investigación o el desarrollo del estudio. El sujeto tiene programada la participación en otro estudio clínico externo a Baxalta con un PEI o un dispositivo en investigación durante el transcurso de este estudio. La participante está dando el pecho o pretende hacerlo durante el transcurso del estudio. El sujeto ha participado en otro estudio clínico que utilizó un PEI o un dispositivo en investigación durante los 30 días anteriores a la inscripción o está programado que participe en otro estudio clínico (a excepción del protocolo 161403 o 161601) con un PEI o un dispositivo en investigación durante el transcurso de este estudio. 6El sujeto es un familiar o empleado del investigador. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety/Tolerability Number (percentage) of subjects experiencing any treatment-emergent serious and/or non-serious adverse events (SAEs and/or AEs, respectively), regardless of causality Number (percentage) of subjects experiencing causally related SAEs and/or AEs Number (percentage) of subjects with serious and/or non-serious adverse reactions (ARs) plus suspected ARs Rate of AEs that may be a result of immune-mediated response to either immunoglobulin,rHuPH20, or other factors as listed in Table 12-1, expressed as number of events per infusion and per subject-year Number (percentage) of infusions associated with treatment-emergent SAEs and/or AEs, regardless of causality Number (percentage) of infusions associated with causally related SAEs and/or AEs Number (percentage) of infusions temporally associated with AEs (defined as AEs occurring during or within 72 hours after completion of an infusion) Number (percentage) of infusions associated with serious and/or non-serious ARs plus suspected ARs Number (percentage) of infusions associated with 1 or more systemic AEs Number (percentage) of infusions associated with 1 or more local infusion site reactions Number and proportion of infusions for which the infusion rate was reduced and/or the infusion was interrupted or stopped due to intolerability and/or AEs Rates of systemic and local AEs, regardless of causality, expressed as number of events per infusion, per subject, and per subject-year Rates of causally related systemic and local AEs, expressed as number of events per infusion, per subject, and per subject-year Rates of systemic and local ARs plus suspected ARs, expressed as number of events per infusion, per subject, and per subject-year Number of subjects with AE(s) that led to discontinuation from study Number and rate per infusion of moderate or severe AEs that may be a result of immune mediated response to either immunoglobulin, rHuPH20 or other factors Immunogenicity Incidence of binding antibodies to rHuPH20 Incidence of neutralizing antibodies to rHuPH20 Number of subjects with a decline of anti-rHuPH20 antibody titers to the antibody titer level at baseline in study 161403 or 161601 and/or to <160 at the study completion or early discontinuation For subjects who have >10,000 titer of binding antibodies to rHuPH20: neutralizing antibodies and cross reactivity with Hyal-1,2 and 4 |
Seguridad/tolerabilidad Número (porcentaje) de sujetos que experimentan acontecimientos adversos graves o no graves (AAG o AA, respectivamente) surgidos durante el tratamiento, independientemente de la causalidad. Número (porcentaje) de sujetos que experimentan AAG o AA relacionados causalmente. Número (porcentaje) de sujetos con reacciones adversas (RA) graves o no graves más sospechas de RA. Tasa de AA que puedan derivarse de la respuesta mediada inmunitariamente a la inmunoglobulina, rHuPH20 u a otros factores enumerados en la tabla 12-1, representados por el número de acontecimientos por infusión y por sujeto-año. Número (porcentaje) de infusiones asociadas con AAG o AA surgidos durante el tratamiento, independientemente de la causalidad. Número (porcentaje) de infusiones asociadas con AAG o AA relacionados causalmente. Número (porcentaje) de infusiones asociadas temporalmente a AA (definidos como AA que ocurren durante la infusión o en las 72 horas siguientes a la finalización de una infusión). Número (porcentaje) de infusiones asociadas a RA graves o no graves más sospechas de RA. Número (porcentaje) de infusiones asociadas a 1 o más AA sistémicos. Número (porcentaje) de infusiones asociadas a 1 o más reacciones locales en el lugar de la infusión. Número y proporción de infusiones en las cuales se redujo la velocidad de infusión o se interrumpió o se detuvo la infusión debido a intolerancia o AA. Tasas de AA locales y sistémicos, independientemente de la causalidad, expresadas en número de acontecimientos por infusión, por sujeto y por sujeto-año. Tasas de AA locales y sistémicos relacionados causalmente, expresados en número de acontecimientos por infusión, por sujeto y por sujeto-año. Tasas de RA locales y sistémicas más sospechas de RA, expresadas en número de acontecimientos por infusión, por sujeto y por sujeto-año. Número de sujetos con AA que causen la interrupción de la participación en el estudio. Número y tasa por infusión de AA moderados o intensos que puedan haber sido resultado de la respuesta mediada por la inmunidad a la inmunoglobulina, rHuPH20 o a otros factores definidos en la tabla 12-1 . Inmunogenicidad Incidencia de anticuerpos de unión frente a rHuPH20. Incidencia de anticuerpos neutralizantes frente a rHuPH20. Número de sujetos con disminución del valor de anticuerpos anti-rHuPH20 hasta el valor inicial de anticuerpos en el estudio clínico 161403 o 161601 al terminar el estudio o finalizarlo anticipadamente. En el caso de los sujetos con valor de anticuerpos de unión a rHuPH20 >10 000: anticuerpos neutralizantes y reactividad cruzada con Hyal-1,2 y 4. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Outcome measures Pharmacokinetics—Serum IgG levels Efficacy measures Proportion subjects who relapse EuroQoL HRU Treatment satisfaction Treatment preference Administration outcomes Number of sites per infusion Maximum volume per infusion site Time to administer the study product (immunoglobulin/rHuPH20) Monthly infusion time Number of subjects/caregivers unable to continue with self/home infusion and reason(s) for this failure. Maximum infusion rates Optional photo recording of infusion procedures |
Medidas de resultado Farmacocinética: niveles séricos de IgG Medidas de eficacia Proporción de sujetos que recaen EuroQoL HRU Satisfacción del tratamiento Preferencia de tratamiento Resultados de la administración Número de centros por infusión Volumen máximo por sitio de infusión Tiempo para administrar el producto del estudio (inmunoglobulina / rHuPH20) Tiempo de infusión mensual Número de sujetos / cuidadores incapaces de continuar con la autoinfusión de la (s) razón (es) por este fracaso. Tasa de infusión máxima Grabación fotográfica opcional de procedimientos de infusión |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Pharmacokinetics Timepoints: Week 1, 2, 13, 26, 39, 52, 65, 78, 91, 104 Efficacy measures Timepoints: Week 13, 26, 39, 52, 65, 78, 91, 104 EuroQoL Timepoints: Baseline, week 26, 52, 78 HRU Timepoints: Baseline, Week 13, 26, 39, 52, 65,78, 91, 104 Treatment satisfaction Timepoints: Baseline, week 26, 52, 78 Treatment preference Timepoints: Baseline, week 26, 52, 78 Administration outcomes Timepoints: Every 2, 3, or 4 weeks (every infusion) |
Farmacocinética timepoints: Semana 1, 2, 13, 26, 39, 52, 65, 78, 91, 104 Medidas de eficacia Timepoints: Semana 13, 26, 39, 52, 65, 78, 91, 104 EuroQoL Timepoints: Línea de base, semana 26, 52, 78 HRU Timepoints: Línea de base, Semana 13, 26, 39, 52, 65, 78, 91, 104 Satisfacción del tratamiento Timepoints: Línea de base, semana 26, 52, 78 Preferencia de tratamiento Timepoints: Línea de base, semana 26, 52, 78 Resultados de la administración Timepoints: Cada 2, 3 o 4 semanas (cada infusión) |
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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 | 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 | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
immunogenicity |
Immunogenicidad |
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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) | No |
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 | 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
| 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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
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 |
Colombia |
Czech Republic |
Denmark |
France |
Germany |
Greece |
Israel |
Italy |
Mexico |
Norway |
Serbia |
Slovakia |
Spain |
Sweden |
Switzerland |
Turkey |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | No |
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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Each subject will have the opportunity to receive HyQvia for a maximum of 2.5 years OR up to 3 years if mandated by regulations |
Cada sujeto tendrá la oportunidad de recibir HyQuia por un máximo de 2,5 años de o hasta 3 años si es requerido por regulación. |
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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 | 5 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 5 |