E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003553 |
E.1.2 | Term | Asthma |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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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 characterize the dose-response relationship of five doses of CSJ117 inhaled daily on lung function, compared with placebo, at the end of the 12-week active-treatment period |
Caractériser la relation dose-réponse de 5 doses de CSJ117 inhalé (1 fois par jour) sur la fonction pulmonaire par rapport au placebo à l'issue de la période de traitement de 12 semaines |
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E.2.2 | Secondary objectives of the trial |
1. To characterize the dose-response relationship of five doses of CSJ117 inhaled daily on FeNO
2. To assess immunogenicity of five doses of CSJ117
3. To characterize the systemic pharmacokinetic (PK) profile of multiple inhaled daily doses of CSJ117
4. To characterize the efficacy of five doses of CSJ117 once daily on peak expiratory flow
5. To characterize the efficacy of five doses of CSJ117 once daily on ACQ-5
6. To characterize the efficacy of five doses of CSJ117 once daily on change from baseline in AQLQ score
7. To characterize the efficacy of five doses of CSJ117 once daily on daytime and nighttime asthma symptoms
8. To characterize the efficacy of five doses of CSJ117 once daily on daily short-acting β-agonist (SABA)
9. To assess the safety of five doses of CSJ117 once daily with respect to adverse events (AE), electrocardiograms (ECGs), vital signs and laboratory tests
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1. Caractériser la relation dose-réponse de 5 doses de CSJ117 sur le monoxyde d’azote dans l’air expiré (FeNO)
2. Evaluer l’immunogénicité de 5 doses de CSJ117
3. Caractériser le profil pharmacocinétique (PK) de doses multiples de CSJ117
4. Caractériser l’efficacité de 5 doses de CSJ117 sur le débit expiratoire de pointe
5. Caractériser l’efficacité de 5 doses de CSJ117 sur le score de contrôle de l’asthme (ACQ-5)
6. Caractériser l’efficacité de 5 doses de CSJ117 sur le score de qualité de vie liée à l’asthme (AQLQ)
7. Caractériser l’efficacité de 5 doses de CSJ117 sur les symptômes diurnes et nocturnes de l’asthme
8. Caractériser l’efficacité de 5 doses de CSJ117 sur l’utilisation quotidienne de bronchodilatateurs bêta-2 stimulants à courte durée d’action (SABA, pour short acting beta agonist)
9. Evaluer la sécurité d’emploi de 5 doses de CSJ117 sur les effets indésirables, électrocardiogrammes, signes vitaux et paramètres biologiques |
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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 |
Pharmacogenetics sub-study. Protocol No.CCSJ117A12201C (Version No.01 dated 26-Mar-2020).
The purpose of genetic research may be to better understand the safety and efficacy of CSJ117, or to learn more about human diseases, or to help develop ways to detect, monitor and treat diseases. |
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E.3 | Principal inclusion criteria |
1. Diagnosed asthma
2. Male and female patients aged >18 and <75 years
3. Patients who have been treated with medium or high dose ICS plus LABA with up to 2 additional controller
4. Morning pre-BD FEV1 value of ≥ 40% and ≤ 85% of the predicted normal
5. A positive reversibility test
6. ACQ-5 score of ≥ 1.5 at screening and end of run-in visits.
7. History of 1 or 2 asthma exacerbations within the 12 months prior to Screening Visit that required treatment with systemic corticosteroids (tablets, suspension or injection).
8. Other protocol-defined inclusion criteria may apply |
1. Asthme documenté et diagnostiqué
2. Hommes et femmes âgé(e)s de ≥ 18 ans et ≤ 75 ans
3. Patients traités par CSI à doses moyennes ou fortes et par LABA, seuls ou en association avec un maximum de 2 traitements de fond additionnels
4. Les valeurs du VEMS mesuré le matin doivent être ≥ 40 % et ≤ 85 % de la valeur théorique
5. La réversibilité du VEMS
6. Score ACQ-5 ≥ 1,5 aux visites de sélection et de fin de de « run-in »
7. Antécédent de 1 ou 2 exacerbation de l’asthme dans les 12 mois précédant la visite de sélection, ayant nécessité un traitement par corticostéroïdes systémiques (comprimés, suspension ou injection)
8. D'autres critères définis dans le protocole peuvent s'appliquer |
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E.4 | Principal exclusion criteria |
1. Patients who have a cigarette smoking history of greater than 10 pack years or current smokers.
2. Pregnant or nursing (lactating) women
3. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using specified methods of
contraception during dosing of study drug and one week after last study drug treatment
4. Patients with a history of immunodeficiency disease or hepatitis B or hepatitis C or HIV.
5. Other protocol-defined exclusion criteria may apply |
1. Antécédents tabagiques (cigarettes) de plus de 10 paquets-années ou patients actuellement fumeurs ou vapoteurs.
2. Femmes enceintes ou qui allaitent
3. Femmes en âge d’avoir des enfants, c’est-à-dire toutes les femmes physiologiquement aptes à être enceintes, sauf si elles utilisent une méthode de contraception efficace pendant toute la période de traitement à l’étude et pendant 1 semaine après l’arrêt du traitement.
4. Antécédents d’immunodéficience, d’hépatite B ou C, ou d’infection par le virus de l’immunodéficience humaine (VIH)
5. D'autres critères définis dans le protocole peuvent s'appliquer |
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E.5 End points |
E.5.1 | Primary end point(s) |
Average change from baseline in pre-dose FEV1 (Forced expiratory volume in 1 second) at Week 8 and Week 12 |
Variation moyenne par rapport à la baseline du VEMS (L) pré-dose à la Semaine 8 et à la Semaine 12 |
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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) |
1. Average change from baseline in FeNO at Week 8 and Week 12.
2. Measurement of Anti-Drug Antibodies (ADA) titers at baseline and during the study (Week 0 [Day 1] to Week 24)
3. Measurement of total CSJ117 serum concentration during the study (Week 0 [Day 1] to Week 24)
4. Change from baseline in peak expiratory flow (PEF; am and pm), as assessed by mean morning and mean evening PEF in each week (average over 7 days) during 12 weeks of treatment
5. Average change from baseline in ACQ-5 score at Week 8 and Week 12.
ACQ-5 (Asthma Control Questionnaire-5) consists of 5 items on symptom assessment. Patients will be asked to recall how their asthma has been during the previous week and to respond to the symptom questions on a 7-point scale (0=no impairment, 6=maximum impairment). The questions are equally weighted and the ACQ-5 score is the mean of the 5 questions: therefore, between 0 (totally controlled) and 6 (severely uncontrolled).
6. Average change from baseline in AQLQ+12 score at Week 8 and Week 12 AQLQ+12 (Asthma Quality of Life Questionnaire) comprises a total of 32 individual questions that span a total of four domains: symptoms, activity limitation, emotional function, and environmental stimuli. Patients are asked to recall their experiences during the previous 2 weeks and to score each item on a 7-point scale (7 = not at all impaired to 1 = severely impaired). The AQLQ+12 yields individual domain scores, which is the mean of all items in each domain, and an overall score, which is the mean of all 32 individual responses. Higher scores indicate less impairment in health related quality of life.
7. Average change from baseline in asthma symptom score at week 8 and week 12. Asthma symptom score consists out of two parts i.e. ADSD (asthma daytime Symptom Diary) and ANSD (asthma nighttime symptom diary) integrated into one. Each part is comprised of 6 items assessing breathing symptoms, chest symptoms, and cough symptoms. All items are assessed using an 11-point numeric rating scale ranging from 0 (‘None’) to 10 (‘As bad as you can imagine’).
8. Change from baseline in number of puffs of SABA (short-acting beta agonists) taken per day in each week (average over 7 days) during 12 weeks active-treatment period |
1. Variation moyenne par rapport à la baseline du monoxyde d’azote dans l’air expiré (FeNO) à la Semaine 8 et à la Semaine 12
2. Titres d’anticorps anti-CSJ117 à la baseline et tout au long de l’étude (de la Semaine 0 [Jour 1] à la Semaine 24
3. Mesure des concentrations sériques totales de CSJ117 pendant l’étude (de la Semaine 0 [Jour 1] à la Semaine 24)
4. Variation par rapport à la baseline du DEP du matin et du DEP du soir, évaluée chaque semaine par la moyenne sur 7 jours du DEP du matin et du DEP du soir pendant les 12 semaines de traitement
5. Variation moyenne par rapport à la baseline du score ACQ-5 à la Semaine 8 et à la Semaine 12
6. Variation moyenne par rapport à la baseline du score AQLQ+12 à la Semaine 8 et à la Semaine 12
7. Variation moyenne par rapport à la baseline des scores de symptômes diurnes ADSD (pour Asthma Daytime Symptom Diary) et des scores de symptômes nocturnes ANSD (pour Asthma Nighttime Symptom Diary) à la Semaine 8 et à la Semaine 12.
8. Variation par rapport à la baseline du nombre de bouffées de SABA quotidiennes (moyenne sur 7 jours) pendant la période de traitement de 12 semaines |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1, 5-7: Baseline, Week 8 and Week 12
2, 3: Baseline (Week 0) and Week 24
4, 8: Baseline, 12 weeks of treatment |
1, 5-7: Baseline, semaine 8 et semaine 12
2, 3: Baseline (semaine 0) et semaine 24
4, 8: Baseline, 12 semaines de traitement |
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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 | Yes |
E.6.10 | Pharmacogenetic | Yes |
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 | 6 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 76 |
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 |
Canada |
Guatemala |
Japan |
Korea, Republic of |
Philippines |
Russian Federation |
United States |
Belgium |
Bulgaria |
Czechia |
France |
Germany |
Hungary |
Italy |
Latvia |
Poland |
Slovakia |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 14 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 14 |