E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cystic Fibrosis-Related Exocrine Pancreatic Insufficiency |
Insuficiencia pancreática exocrina debida a fibrosis quística |
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E.1.1.1 | Medical condition in easily understood language |
Maldigestion of diatery macronutients (pancreas not producing enough enzymes for digestion of fat, sugars and proteins) in Cystic Fibrosis |
Mala digestión de los macronutrientes alimenticios (el páncreas no produce las suficientes enzimas para la digestión de la grasa, azúcares y proteínas) en la Fibrosis Quística. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
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 primary objective of this study is to evaluate the safety of long-term use of liprotamase in the management of Cystic Fibrosis-Related Exocrine Pancreatic Insufficiency (EPI). Safety will be evaluated based on the occurrence of adverse events (AEs) and serious AEs (SAEs); including but not limited to abnormal laboratory results, abnormal findings in physical examinations and abnormal vital signs deemed clinically significant by the investigator. |
El objetivo principal de este estudio es evaluar la seguridad del uso prolongado de liprotamasa en el tratamiento de Insuficiencia Pancreática Exocrina (IPE) debida a la fibrosis quística. La seguridad se evaluará en función de los acontecimientos adversos (AA) y los AA graves (AAG), incluido, entre otros, resultados anómalos de laboratorio, resultados anómalos de las exploraciones físicas y constantes vitales anómalas que el investigador considere clínicamente significativos. |
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E.2.2 | Secondary objectives of the trial |
The secondary endpoints will include: • Change in weight, height, and BMI from baseline. • Changes in measures of growth including weight, height, and BMI relative to population anthropomorphic measures. • Signs and symptoms of malabsorption including stool frequency, stool consistency, bloating, steatorrhea, abdominal pain, and flatulence compared with baseline. |
Los criterios secundarios de valoración serán: • Cambio en el peso, estatura e IMC respecto al inicio del estudio. • Cambio en las medidas de crecimiento, incluyendo peso, estatura e IMC, con respecto a las medidas antropométricas de la población. • Signos y síntomas de malabsorción, incluyendo frecuencia y consistencia de las deposiciones, distención abdominal, esteatorrea, dolor abdominal y flatulencia en comparación con el inicio del estudio. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects are eligible for enrollment if they meet the following inclusion criteria: 1. Male or female subjects who received liprotamase and completed Study AN-EPI3331. 2. Signed informed consent by subject and/or subject’s legally authorized representative. |
Los sujetos son aptos para su participación en el estudio si cumplen los siguientes criterios de inclusión: 1. Sujetos de ambos sexos que recibieron liprotamasa y completaron el estudio AN-EPI3331. 2. Consentimiento informado firmado por el sujeto y/o por su representante legal. |
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E.4 | Principal exclusion criteria |
1. Any medical, psychological, or social condition that, at the discretion of the investigator, may put the subject at increased risk by participating in this study or confound interpretation of study results. 2. Treatment with any PERT other than study drug, investigational drugs, or devices 3. Females who are nursing, pregnant, intending to become pregnant, or intending to nurse during the time of the study, or who have a positive pregnancy test at Visit Day 1. All sexually-active subjects of reproductive potential are required to remain on a reliable method of birth control. Females and males are required to continue using a reliable method of birth control throughout the study, and for at least 3 months following completion of study therapy. A reliable method of birth control is defined as one of the following: oral or injectable contraceptives, intrauterine device, contraceptive implants, tubal ligation, hysterectomy, or a double-barrier method (diaphragm with spermicidal foam or jelly, or a condom), abstinence or vasectomy. |
1. Cualquier afección médica, psicológica o social que, en opinión del investigador, pueda suponer para el sujeto un mayor riesgo debido a la participación en este estudio o confunda la interpretación de los resultados del estudio. 2. Tratamiento con cualquier terapia de sustitución de enzimas pancreáticas distinto de la medicación de estudio, fármacos en investigación o dispositivos. 3. Mujeres en periodo de lactancia, embarazadas, con intención de quedarse embarazadas o de dar el pecho durante el estudio, o que tengan una prueba de embarazo positiva en la Visita Día 1. Todos los sujetos sexualmente activos potencialmente fértiles deben usar un método fiable de control de la natalidad. Tanto mujeres como varones deben continuar utilizando un método fiable de control de la natalidad durante todo el estudio, y durante al menos 3 meses después de completar el tratamiento del estudio. Un método fiable de control de la natalidad se define como uno de los siguientes: anticonceptivos orales o inyectables, dispositivo intrauterino, implantes anticonceptivos, ligadura de trompas, histerectomía o método de doble barrera (diafragma con espuma o gel espermicida, o preservativo), abstinencia o vasectomía. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective of this study is to evaluate the safety of long-term use of liprotamase in the management of EPI due to CF amongst subjects who received liprotamase and completed the prior study with liprotamase (AN-EPI3331). Safety will be evaluated based on adverse events (AEs) and serious AEs (SAEs); including but not limited to abnormal laboratory results, abnormal findings in physical examinations, and abnormal vital signs deemed clinically significant by the investigator. By-subject listings of all AEs, including abnormal and clinically significant vital sign parameters and physical examination results will be presented. |
El objetivo principal de este estudio es evaluar la seguridad del uso prolongado de liprotamasa en el tratamiento de Insuficiencia Pancreática Exocrina (IPE) debida a la fibrosis quística (FQ) entre los sujetos que recibieron liprotamasa y completaron el estudio previo con liprotamasa (AN-EPI3331). La seguridad se evaluará en función de los acontecimientos adversos (AA) y los AA graves (AAG), incluido, entre otros, resultados anómalos de laboratorio, resultados anómalos de las exploraciones físicas y constantes vitales anómalas que el investigador considere clínicamente significativos. Se presentarán los listados por sujeto de todos los AAs, incluyendo parámetros de constantes vitales anómalos y clínicamente significativos y resultados de las exploraciones físicas. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At each study Visit during the treatment period. |
En cada visita del estudio durante el período de tratamiento. |
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E.5.2 | Secondary end point(s) |
In this study efficacy will be evaluated from measures of body weight and BMI (for adults) and growth (for pediatric subjects) relative to baseline and/or relative to published population growth charts. In addition, efficacy (i.e. control of EPI) will be evaluated from the signs and symptoms of malabsorption. The secondary endpoints will include: • Change in weight, height, and BMI from baseline. • Changes in measures of growth including weight, height, and BMI relative to population anthropomorphic measures. • Signs and symptoms of malabsorption including stool frequency, stool consistency, bloating, steatorrhea, abdominal pain, and flatulence compared with baseline. For efficacy analyses of change from baseline, baseline will be defined as the last observation prior to initiation of liprotamase dosing. |
En este estudio se evaluará la eficacia a partir de medidas de peso corporal y el IMC (para adultos) y el crecimiento (para pacientes pediátricos) en relación con el valor inicial y / o en relación con las tablas de crecimiento de población publicadas. Además, la eficacia (es decir, el control de la IPE) se evaluará a partir de los signos y síntomas de mala absorción. Los criterios secundarios de valoración serán los siguientes: • Cambio en el peso, estatura e IMC respecto al inicio del estudio. • Cambio en las medidas de crecimiento, incluyendo peso, estatura e IMC, con respecto a las medidas antropométricas de la población. • Signos y síntomas de malabsorción, incluyendo frecuencia y consistencia de las deposiciones, distención abdominal, esteatorrea, dolor abdominal y flatulencia en comparación con el inicio del estudio. Para el análisis de eficacia del cambio desde el valor inicial, el valor inicial se definirá como la última observación antes del inicio de la dosificación de liprotamasa. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At each study Visit during the treatment period. |
En cada visita del estudio durante el período de tratamiento. |
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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 | 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 | 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.8.3 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
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 |
Israel |
United States |
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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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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |