E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of Alpha-Mannosidosis |
Tratamiento de alfa-manosidosis |
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E.1.1.1 | Medical condition in easily understood language |
Treatement of Alpha-Mannosidosis |
Tratamiento de alfa-manosidosis |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
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 overall objective of this trial is to evaluate the efficacy and safety of repeated Lamazym i.v. treatment, compared with placebo, in subjects 5-35 years of age with alpha-Mannosidosis |
El objetivo es evaluar la eficacia y la seguridad del tratamiento intravenoso (i.v.) repetido con Lamazym en pacientes de 5-35 años con alfa-manosidosis. |
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E.2.2 | Secondary objectives of the trial |
PK evaluation |
Farmacocinética |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject or subjects legally authorized guardian(s) must provide signed, informed consent prior to performing any trial-related activities 2. The subject and his/her guardian(s) must have the ability to comply with the protocol 3. The subject must have a confirmed diagnosis of alpha-mannosidosis as defined by alpha-mannosidase activity < 10% of normal activity (historical data) 4. The subject must have an age at the time of screening ? 5 years and ? 35 years 5. The subject must have the ability to physically and mentally cooperate in the tests 6. The subject must have an ECHO without abnormalities that, in the opinion of the Investigator, would preclude participation in the trial |
1. El paciente o su(s) tutor(es) autorizado(s) legalmente deberán firmar y entregar el consentimiento informado antes de la realización de actividades relacionadas con el ensayo. 2. El paciente y su(s) tutor(es) deberán tener la capacidad para cumplir el protocolo. 3. El paciente deberá tener un diagnóstico confirmado de alfa-manosidosis definido por una actividad de la alfa-manosidasa < 10 % de la actividad normal (datos históricos). 4. El paciente deberá tener, en el momento de la selección, una edad comprendida entre 5 y 35 años. 5. El paciente deberá tener la capacidad de cooperar física e intelectualmente en las pruebas. 6. El paciente debe tener una ECO sin anomalías que, en opinión del investigador, descarten la participación en el ensayo. |
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E.4 | Principal exclusion criteria |
1. The subjects diagnosis cannot be confirmed by alpha-mannosidase activity < 10% of normal activity 2. The subject cannot walk without support 3. Presence of known chromosomal abnormality and syndromes affecting psychomotor development, other than alpha-mannosidosis 4. History of BMT 5. Presence of known clinically significant cardiovascular, hepatic, pulmonary, or renal disease or other medical conditions that, in the opinion of the Investigator, would preclude participation in the trial 6. Any other medical condition or serious intercurrent illness, or extenuating circumstance that, in the opinion of the Investigator, would preclude participation in the trial 7. Pregnancy: Pregnant woman is excluded. Before start of the treatment the investigators will for women of childbearing potential perform a pregnancy test and decide whether or not there is a need for contraception 8. Psychosis any psychotic disease, also in remission, is an exclusion criteria 9. Planned major surgery that, in the opinion of the Investigator, would preclude participation in the trial 10. Participation in other interventional trials testing IMP (including Lamazym) within the last 3 months 11. Adult patients who, in the opinion of the Investigator, would be unable to give consent, and who does not have any legal protection or guardianship 12. Total IgE >800 IU/ml 13. Known allergy to the IMP or any excipients (Sodium-Phosphate, Glycine, Mannitol) |
1. El diagnóstico de los pacientes no puede confirmarse por una actividad de la alfa-manosidasa < 10 % de la actividad normal. 2. El paciente no puede caminar sin apoyo. 3. Presencia de anomalía cromosómica conocida y síndromes que afecten al desarrollo psicomotor distintos de la alfa-manosidosis. 4. Antecedentes de TMO. 5. Presencia de enfermedades cardiovasculares, hepáticas, pulmonares o renales conocidas y clínicamente significativas u otras afecciones que, en opinión del investigador, descarten la participación en el ensayo. 6. Cualquier otra afección o enfermedad intercurrente grave o circunstancia atenuante que, en opinión del investigador, descarte la participación en el ensayo. 7. Embarazo: Las embarazadas están excluidas. Antes de iniciar el tratamiento, los investigadores realizarán una prueba de embarazo a las mujeres en edad de procrear y decidirán si es necesario utilizar métodos anticonceptivos. 8. Psicosis: cualquier enfermedad psicótica, aunque esté en remisión, constituye un criterio de exclusión. 9. Intervención quirúrgica mayor prevista que, en opinión del investigador, descarte la participación en el ensayo. 10. Participación en otros ensayos de intervención que prueben PEI (incluido Lamazym) en los últimos 3 meses. 11. Pacientes adultos que, en opinión del investigador, no vayan a ser capaces de prestar su consentimiento y que no tengan tutela ni protección legal. 12. Total IgE > 800 UI/ml 13. Alergia conocida al PEI o a cualquier excipiente (fosfato de sodio, glicina, manitol). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Efficacy Endpoints is change from baseline in the active treated group versus the placebo group: ? The level of oligosaccharides in serum ? 3-minute stair climb test (3MSCT) |
Los criterios principales de valoración de la eficacia son el cambio desde basal en el grupo de tratamiento activo versus el grupo de placebo de: - la concentración sérica de oligosacáridos, - la prueba de tres minutos subiendo escaleras (P3MSE). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Efficacy will be assessed at the Danish site at baseline (prior to first dose), as midterm evaluation (after 26+/-3 weeks, referred to as midterm evaluation or visit 26a), and as end evaluation (after 52±3 weeks, referred to as end evaluation or visit 52a). |
La eficacia se evaluará en el hospital de Dinamarca en visita basal (antes de la primera dosis), a medio plazo (despues de 26 +/- 3 semanas; referida como evaluación a medio plazo o visita 26a), y una evaluación final (después de 52 +/- 3 semanas, referida como evaluación final o visita 52a) |
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E.5.2 | Secondary end point(s) |
Prioritized Secondary Efficacy Endpoints: ? Forced Vital Capacity (FVC) ? 6 minute walk test (6MWT)
Other Secondary Efficacy Endpoints: ? Bruininks-Oseretsky test of Motor Proficiency (BOT2) ? Leiter R ? Cerebrospinal fluid biomarkers incl oligosaccharide and standard tests ? Pulmonary Function Tests ? Pure tone audiometry (PTA) ? Questionnaires (CHAQ and EQ-5D)
Safety Endpoints: ? Adverse events (AEs) ? Vital signs and change in physical examination ? Clinical laboratory parameters (hematology, biochemistry and urinalysis) ? Development of Lamazym antibodies and neutralizing/inhibitory antibodies
Pharmacokinetic endpoints: ? Pharmacokinetics (PK) |
Los criterios secundarios priorizados de valoración la eficacia del ensayo son la evaluación de: - la capacidad vital forzada (CVF), - la prueba de seis minutos caminando (P6MC).
Otros criterios secundarios de valoración de la eficacia: - prueba de competencia motriz de Bruininks-Oseretsky, - Leiter R, - biomarcadores del líquido cefalorraquídeo, incluidos análisis de oligosacáridos y pruebas habituales, - pruebas funcionales respiratorias, - audiometría de tonos puros, - cuestionarios
Los criterios de valoración de la seguridad del ensayo son la evaluación de: - acontecimientos adversos, - constantes vitales y cambio en la exploración física, - variables de laboratorio clínico (hematología, bioquímica y análisis de orina), - la aparición de anticuerpos contra Lamazym y de anticuerpos neutralizantes o inhibidores.
Criterios de valoración farmacocinéticos - Farmacocinética (FC). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Efficacy will be assessed at the Danish site at baseline (prior to first dose), as midterm evaluation (after 26±3 weeks, referred to as midterm evaluation or visit 26a), and as end evaluation (after 52±3 weeks, referred to as end evaluation or visit 52a). Safety will be assessed at every visit. PK will be analyzed at visit 1. |
La eficacia se evaluará en el hospital de Dinamarca en visita basal (antes de la primera dosis), a medio plazo (despues de 26 +/- 3 semanas; referida como evaluación a medio plazo o visita 26a), y una evaluación final (después de 52 +/- 3 semanas, referida como evaluación final o visita 52a) La seguridad se evaluará en cada visita La farmacocinética se analizará en la visita 1 |
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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 | 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 | 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 | 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 | 8 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 is the date when all subjects have completed their EOT visit and this is defined as the End of Trial date. |
Ultima visita del ultimo paciente: cuando todos los pacientes han completado la visita de fin de estudio |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 12 |
E.8.9.2 | In all countries concerned by the trial days | 0 |