E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-Cystic Fibrosis Bronchiectasis |
Bronquiectasia no debida a fibrosis quística |
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E.1.1.1 | Medical condition in easily understood language |
Non-Cystic Fibrosis Bronchiectasis |
Bronquiectasia no debida a fibrosis quística |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the effect of INS1007 compared with placebo on time to first pulmonary exacerbation over the 24-week treatment period. To assess the safety and tolerability of INS1007 relative to placebo based on adverse events (AEs), vital signs and electrocardiogram (ECG) measurements, physical exams and clinical laboratory evaluations. |
Evaluar el efecto del INS1007 comparado con placebo sobre el tiempo hasta la primera exacerbación pulmonar a lo largo del periodo de tratamiento de 24 semanas. Evaluar la seguridad y tolerabilidad de INS1007 comparadas con placebo, basándose en los acontecimientos adversos (AA), las constantes vitales y las medidas del electrocardiograma (ECG), exploraciones físicas y exámenes de laboratorio clínico. |
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E.2.2 | Secondary objectives of the trial |
1. To evaluate the effect of INS1007 compared with placebo on quality of life (QOL), as assessed by the Quality of Life Questionnaire-Bronchiectasis (QOL-B), Respiratory Symptoms Domain score, over the 24-week treatment period. 2. To evaluate the effect of INS1007 compared with placebo on lung function, as measured by forced expiratory volume in 1 second (FEV1), over the 24-week treatment period. 3. To evaluate the effect of INS1007 compared with placebo on the concentration of active neutrophil elastase (NE) in sputum, as measured by the difference between the pre-treatment concentration (defined as the average of the values at Screening and Day 1) and on-treatment concentration (defined as the average of the values at weeks 12 and 24). 4. To evaluate the effect of INS1007 compared with placebo on the rate of pulmonary exacerbations over the 24-week treatment period. |
1. Evaluar el efecto del INS1007 comparado con placebo sobre la calidad de vida (CdV) según evaluación mediante el Cuestionario sobre calidad de vida-Bronquiectasia (QOL-B), escala del dominio de síntomas respiratorios, a lo largo del periodo de tratamiento de 24 semanas. 2. Evaluar el efecto de INS1007 comparado con placebo sobre la función pulmonar, medida mediante volumen espiratorio forzado en 1 segundo (VEF1) a lo largo del periodo de tratamiento de 24 semanas. 3. Evaluar el efecto de INS1007 comparado con placebo en la concentración de elastasa de neutrófilos (EN) activa en el esputo, medida según la diferencia entre la concentración pretratamiento (definida como la media de valores de los días de la selección y el día 1) y la concentración con tratamiento (definida como la media de los valores la semanas 12 y 24). 4. Evaluar el efecto de INS1007 comparado con placebo en la tasa de exacerbaciones pulmonares a lo largo del periodo de tratamiento de 24 semanas. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
A PK sub-study will be conducted at a selected number of sites globally. Subjects who enroll at the selected sites will undergo intensive PK sampling. A maximum of 36 subjects will be included in the PK sub-study. For subjects who participate in the PK sub-study, the visit window for Visit 4 will be ± 5 days.
Pharmacokinetic Objectives: 1. To evaluate the pharmacokinetics (PK) of INS1007. 2. To assess the relationship between PK measures for INS1007 and efficacy, safety and biomarker measures (e.g., concentrations of active NE in sputum and reagent-stimulated blood). |
Se llevará a cabo un subestudio FC en un cierto número de centros a nivel global. Los sujetos que se inscriban en los centros seleccionados (ningún centro en España) se someterán a un muestreo intensivo para FC. Se incluirá un máximo de 36 sujetos en el subestudio FC. Para los sujetos que participen en el subestudio FC, el margen de días de visita para la visita 4 será de ± 5 días.
Objetivos de Farmacocinética: 1. Evaluar la farmacocinética (FC) de INS1007. 2. Evaluar la relación entre las medidas FC para INS1007 y las medidas de eficacia, seguridad y biomarcadores (p.ej., concentraciones de EN activa en esputo y sangre estimulada con reactivos). |
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E.3 | Principal inclusion criteria |
Subjects who have given their signed, informed consent, are male or female between 18 and 85 years of age (inclusive) with a body mass index > 18.5 at Screening (Visit 1) and have a clinical history consistent with NCFBE will be eligible for enrollment in the study. |
Los sujetos que hayan proporcionado su consentimiento informado firmado, sean varones o mujeres de entre 18 y 85 años de edad (inclusive) con un índice de masa corporal > 18,5 en la selección (visita 1) y tengan un historial clínico coherente con NCFBE serán aptos para su inclusión en el estudio. |
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E.4 | Principal exclusion criteria |
Subjects who have a primary diagnosis of chronic obstructive pulmonary disease or asthma, have bronchiectasis due to cystic fibrosis, hypogammaglobulinemia, common variable immunodeficiency, or α1-antitrypsin deficiency, are current smokers as defined per Centers for Disease Control and Prevention criteria, or currently being treated for a nontuberculous mycobacterial lung infection, allergic bronchopulmonary aspergillosis, or tuberculosis will not be eligible for enrollment in the study. |
Los sujetos con diagnóstico primario de enfermedad pulmonar obstructiva crónica o asma, que padezcan bronquiectasia debida a fibrosis quística, hipogammaglobulinemia, inmunodeficiencia variable común, o déficit de α1-antitripsina, sean fumadores habituales según la definición de los criterios de los Centros para el Control y la Prevención de Enfermedades, o estén siendo tratados actualmente por una infección pulmonar por micobacteria no tuberculosa, aspergilosis broncopulmonar alérgica o tuberculosis, no serán aptos para su inclusión en el estudio. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the time to the first pulmonary exacerbation over the 24-week treatment period.
Pulmonary exacerbation definition - A pulmonary exacerbation in this study is defined as having 3 or more of the following symptoms for at least 48 hours resulting in a physician’s decision to prescribe antibiotics. 1. Increased cough; 2. Increased sputum volume or change in sputum consistency; 3. Increased sputum purulence; 4. Increased breathlessness and/or decreased exercise tolerance; 5. Fatigue and/or malaise; 6. Hemoptysis.
Subjects on chronic macrolide therapy whose only change in therapy is dose or frequency adjustment will not meet the definition of exacerbation. |
El criterio de valoración principal es el tiempo que transcurre hasta la primera exacerbación pulmonar a lo largo de las 24 semanas de tratamiento. Definición de exacerbación pulmonar. Una exacerbación pulmonar se define en este estudio como tener 3 o más de los siguientes síntomas durante al menos 48 horas que da como resultado que un médico decida prescribir antibióticos. 1. Aumento de la tos; 2. aumento del volumen de esputo o cambio en su consistencia; 3. aumento de la purulencia del esputo; 4. aumento de la disnea (falta de aliento) y/o disminución de la tolerancia al ejercicio; 5. fatiga y/o malestar general; 6. hemoptisis (sangre al toser).
Los sujetos con tratamiento crónico con macrólidos cuyo único cambio en el tratamiento sea el ajuste de la dosis o la frecuencia no cumplen con la definición de exacerbación. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The time to the first pulmonary exacerbation over the 24-week treatment period. |
El tiempo que transcurre hasta la primera exacerbación pulmonar a lo largo de las 24 semanas de tratamiento. |
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E.5.2 | Secondary end point(s) |
1. Change from Baseline in QOL-B Respiratory Symptoms Domain score over the 24-week treatment period. 2. Change from Screening in post-bronchodilator FEV1 over the 24-week treatment period. 3. Change in concentration of active NE in sputum from pre-treatment (defined as the average of Screening and Day 1 concentrations) to on-treatment (defined as the average of Week 12 and Week 24 concentrations). 4. Rate of pulmonary exacerbations (number of events per person-time) over the 24-week treatment period. |
1. Cambio respecto al inicio en la escala del dominio de síntomas respiratorios del QOL-B a lo largo de las 24 semanas de tratamiento. 2. Cambio respecto a la selección en el VEF1 posbroncodilatador a lo largo de las 24 semanas de tratamiento. 3. Cambio en la concentración de EN activa en esputo desde el pretratamiento (definida como la media de las concentraciones de la selección y del día 1) al periodo de tratamiento (definida como la media entre las concentraciones de la semana 12 y la 24). 4. Tasa de exacerbaciones pulmonares (número de acontecimientos por persona-tiempo) a lo largo del periodo de tratamiento de 24 semanas. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Over the 24-week treatment period. |
A lo largo de las 24 semanas del periodo 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 | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | 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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 69 |
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 |
Australia |
Bulgaria |
Canada |
Denmark |
France |
Germany |
Italy |
Korea, Republic of |
Netherlands |
New Zealand |
Poland |
Singapore |
Spain |
Sweden |
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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The EOS is defined as either the date of the last visit of the last subject to complete the post-dosing follow-up (Visit 10), or the date of receipt of the last data point from the last subject that is required for primary, secondary and/or exploratory analysis, as pre-specified in the protocol, whichever is the later date. |
El fin de estudio se define como o bien la fecha de la última visita del ultimo paciente en completar el seguimiento después del tratamiento (Visita 10) o bien la fecha de recepción del último dato del último sujeto que se requiera para los análisis de objetivos primarios, secundarios o exploratorios, tal y como se especifica en el protocol, lo que ocurra más tarde. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |