E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Mucopolysaccharidosis Type IVA |
Mucopolisacaridosis IVA |
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E.1.1.1 | Medical condition in easily understood language |
Morquio A Syndrome |
Síndrome de Morquio A |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028095 |
E.1.2 | Term | Mucopolysaccharidosis IV |
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 efficacy of BMN 110 administration at 2.0 mg/kg/qw and 2.0 mg/kg/qow in patients with MPS IVA. |
Evaluar la seguridad y la eficacia a largo plazo de la administración de 2,0 mg/kg/todas las semanas y 2,0 mg/kg/cada dos semanas de BMN 110 en pacientes con MPS IVA. |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the long-term effect of BMN 110 administration at 2.0 mg/kg/qw and 2.0 mg/kg/qow on changes in biochemical markers of inflammation and bone and cartilage metabolism, in patients with MPS IVA. - To evaluate patient perception of impairment and improvement at 2.0 mg/kg/qw and 2.0 mg/kg/qow in patients with MPS IVA. |
- Evaluar el efecto a largo plazo de la administración de 2,0 mg/kg/todas las semanas y de 2,0 mg/kg/cada dos semanas de BMN 110 sobre los cambios en los marcadores bioquímicos de inflamación y el metabolismo de los huesos y cartílagos en pacientes con MPS IVA. - Evaluar la percepción de los pacientes en cuanto a deterioro o mejoría con 2,0 mg/kg todas las semanas y 2,0 mg/kg/cada dos semanas en pacientes con MPS IV A. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
? Must have completed MOR-004. ? Is willing and able to provide written, signed informed consent. Or, in the case of patients under the age of 18 (or other age as defined by regional law or regulation), provide written assent (if required) and have written informed consent, signed by a legally authorized representative, after the nature of the study has been explained, and prior to performance of research-related procedures. ? If sexually active, must be willing to use an acceptable method of contraception while participating in the study. ? If female, of childbearing potential, must have a negative pregnancy test at Baseline and be willing to have additional pregnancy tests done during the study. |
- Debe haber completado MOR-004. - Estar dispuesto y poder otorgar un consentimiento informado firmado por escrito. O, en el caso de los pacientes menores de 18 (u otra edad según lo defina la ley o normativa regional), otorgar el asentimiento por escrito (si fuera necesario) y hacer que un representante legalmente autorizado firme el consentimiento informado, después de que se haya explicado la naturaleza del estudio y antes de la realización de los procedimientos relacionados con la investigación. - Si lleva una vida sexual activa, debe estar dispuesto a usar un método aceptado de anticoncepción mientras participa en el estudio. - Si es mujer con capacidad de concebir debe tener un resultado negativo en la prueba de embarazo al inicio y estar dispuesta a realizarse pruebas de embarazo adicionales durante el estudio. |
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E.4 | Principal exclusion criteria |
? Is pregnant or breastfeeding, at Baseline, or planning to become pregnant (self or partner) at any time during the study. ? Has used any investigational product (other than BMN 110 in MOR-004), or investigational medical device, within 30 days prior to Baseline; or is required to use any investigational agent prior to completion of all scheduled study assessments. ? Was enrolled in a previous BMN 110 study, other than MOR-004. ? Has a concurrent disease or condition, including but not limited to, symptomatic cervical spine instability, clinically significant spinal cord compression, or severe cardiac disease that would interfere with study participation, or pose a safety risk, as determined by the Investigator. ? Has any condition that, in the view of the Investigator, places the patient at high risk of poor treatment compliance or of not completing the study. |
- Está embarazada o en periodo de lactancia, al inicio, o tiene planes de embarazo (personal o su pareja) en cualquier momento durante el estudio. - Ha usado cualquier producto en investigación (que no sea BMN 110 en MOR-004), o un dispositivo médico en investigación, dentro de los 30 días previos al inicio; o se requiere que use un agente en investigación antes de completar todas las evaluaciones del estudio programadas. - Participó en un estudio de BMN 110 anterior, distinto de MOR-004. - Tiene una enfermedad o afección concurrente, por ejemplo, inestabilidad sintomática de la columna cervical, compresión clínicamente significativa de la columna dorsal o enfermedad cardíaca grave que interferiría con la participación en el estudio, o representaría un riesgo para la seguridad, según la determinación del investigador. - Tiene una afección que, en opinión del investigador, coloca al paciente en alto riesgo de cumplir con el tratamiento de manera deficiente o de no completar el estudio. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy Variables: ? endurance tests: ? 6 minute walk (6MW) test ? 3 minute stair climb (3MSC) test ? urine KS concentration (normalized to creatinine) ? respiratory function tests: ? forced expiratory time (FET) ? forced expiratory volume in 1 second (FEV1) ? forced inspiratory vital capacity (FIVC) ? forced vital capacity (FVC) ? maximum voluntary ventilation (MVV) ? anthropometric measurements (standing height, length, sitting height, and weight) ? skeletal X-rays of lumbar spine and lower extremity ? MPS Health Assessment Questionnaire ? audiometry examinations Safety Variables: ? adverse events (AEs) ? standard clinical laboratory tests (serum chemistry, hematology, and urinalysis) ? vital signs ? echocardiograms ? electrocardiograms (ECGs) ? routine physical examinations (including standard neurologic examination) ? concomitant medications ? immunogenicity tests ? cervical spine (flexion?extension) X-rays |
Variables de eficacia: - pruebas de resistencia: prueba de caminata de 6 minutos (6MW) y prueba de subida de escaleras de 3 minutos (3MSC) - concentración de KS en orina (normalizada por creatinina) - pruebas de la función respiratoria: – tiempo espiratorio forzado (TEF) – volumen espiratorio forzado en 1 segundo (VEF1) – capacidad vital inspiratoria forzada (CVIF) – capacidad vital forzada (CVF) – ventilación voluntaria máxima (VVM) mediciones antropométricas (estatura de pie, longitud, estatura sentado y peso) - radiografías del esqueleto de la columna lumbar y las extremidades inferiores (las radiografías de las extremidades inferiores se realizan solamente para pacientes de ≤ 20 años de edad) - Cuestionario de evaluación de salud de MPS exámenes de audiometría Variables de seguridad: acontecimientos adversos (AA) análisis de laboratorio clínico estándar (bioquímica sérica, hematología y análisis de orina) constantes vitales ecocardiogramas electrocardiogramas (ECG) exploraciones físicas de rutina, incluido examen neurológico estándar medicación concomitante pruebas de inmunogenicidad radiografías de columna cervical (flexión–extensión) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
? 6MW test, 3MSC test: baseline, wk 12, every 24 wks in Part 1, every 48 wks in Part 2 ? respiratory function tests: baseline, every 24 wks in Part 1, every 48 wks in Part 2 ? anthropometric measurements, MPS Health Assessment Questionnaire, audiometry examinations: baseline, every 24 wks in Part 1 and Part 2 ? adverse events, vital signs, concomitant medications: baseline, weekly in Part 1, weekly or every other week in Part 2 ? echocardiograms, electrocardiograms: baseline, every 48 wks in Part 2 ? routine physical examinations, immunogenicity tests, standard clinical laboratory tests, urine KS concentration: baseline, every 12 wks in Part 1, every 24 wks in Part 2 ? x-rays of cervical spine, lumbar spine and lower extremity: baseline, every 72 wks in Part 2 |
-pruebas de 6MWy3MSC: línea de base,12 semanas(S),cada 24S en la Parte 1,cada 48S en la Parte 2 -pruebas de función respiratoria: línea de base, cada 24S en la Parte 1,cada 48S en de la Parte 2 -medidas antropométricas, MPSCuestionario de Evaluación de Salud, exámenes de audiometría: línea de base,cada 24S en la Parte 1yParte 2 -eventos adversos, signos vitales, medicación concomitante: inicio, cada S en la Parte 1, cada S o cada 2S en la Parte 2 -eco y electrocardiogramas: línea de base, cada 48S de la Parte 2 -exámenes físicos de rutina, pruebas de inmunogenicidad y estándar de lab clínico, orina Concentración KS: línea de base, cada 12S en la Parte 1, cada 24S en la Parte 2 -radiografías de la columna cervical,lumbar y extremidades inferiores: línea de base, cada 72S en la Parte 2 |
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E.5.2 | Secondary end point(s) |
Exploratory Variables: ? blood inflammatory biomarkers ? blood biochemical markers of bone and cartilage metabolism ? Patient Impression Questionnaire (PIQ) |
Variables exploratorias: biomarcadores inflamatorios en sangre marcadores bioquímicos sanguíneos del metabolismo de los huesos y cartílagos Cuestionario de Impresiones del paciente (CIP) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Exploratory Variables: ? blood inflammatory biomarkers, and blood biochemical markers of bone and cartilage metabolism: baseline, every 24 wks in Part 1 and Part 2 ? Patient Impression Questionnaire (PIQ) will be done at Baseline and only at Week 24 within 1 hour (± 15 minutes) following the second 3MSC test. |
Variables exploratorias: biomarcadores inflamatorios en sangre, y la sangre marcadores bioquímicos del metabolismo óseo y cartílago: línea de base, cada 24 semanas en la Parte 1 y Parte 2 ? Cuestionario Impression Paciente (PAA) se hará en el momento basal y sólo en la semana 24 en 1 hora (± 15 minutos) después de la segunda prueba 3MSC. |
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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 | Yes |
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) | 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 | 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 |
Part 1: randomised double blind until optimal BMN 110 dose; Part 2: open-label BMN 110 treatment |
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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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
2.0 mg/kg/qw or 2.0 mg/kg/qow BMN110 |
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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 | 19 |
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 |
Argentina |
Australia |
Brazil |
Canada |
Colombia |
Denmark |
France |
Germany |
Italy |
Japan |
Korea, Republic of |
Netherlands |
Norway |
Portugal |
Qatar |
Saudi Arabia |
Taiwan |
United Kingdom |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 9 |
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 | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |