E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
|
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 | 17.1 |
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 |
|
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 efficacy of 20 mg ADC3680 OD compared with placebo in improving lung function (FEV1) in subjects with inadequately-controlled asthma despite treatment with ICS controller therapy, in the 10 week treatment period (Visit 3 to Visit 6).
To evaluate the effect of adding 10 mg montelukast OD to 20 mg ADC3680 OD on lung function (FEV1) in the 2 week extension period (Visit 6 to Visit 7). |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of 20 mg ADC3680 OD compared with placebo on asthma symptoms (ACQ), other measures of lung function, frequency of severe exacerbations, and reliever therapy use in the 10 week treatment period (Visit 3 to Visit 6).
To evaluate the effects of 20 mg ADC3680 OD compared with placebo on blood eosinophil counts and serum IgE levels in the 10 week treatment period (Visit 3 to Visit 6).
To evaluate the effect of adding 10 mg montelukast OD to 20 mg ADC3680 OD on asthma symptoms (ACQ), other measures of lung function and reliever therapy use in the 2 week extension period (Visit 6 to Visit 7).
To evaluate the effect of adding 10 mg montelukast OD to 20 mg ADC3680 OD on blood eosinophil counts in the 2 week extension period (Visit 6 to Visit 7).
To assess the safety and tolerability of ADC3680 in subjects with inadequately-controlled asthma, both alone and in combination with montelukast. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Male or female subjects aged 18 to 50 years inclusive.
A diagnosis of asthma according to the GINA guidelines, including a demonstration of reversible airway obstruction at screening (Visit 2) or randomisation (Visit 3).
Reversible airway obstruction is defined as either a post-bronchodilator increase in FEV1 of ≥ 12% and ≥ 200 ml over the subject’s pre-bronchodilator value in litres; or an increase of ≥ 10% in FEV1 % predicted when compared with the subject’s pre-bronchodilator value.
Subjects with a pre-bronchodilator FEV1 value ≥ 40% and ≤ 85% of the predicted normal value at screening (Visit 2) and baseline (Visit 3).
A score of 1.5 or greater on the Asthma Control Questionnaire at screening (Visit 2) and at baseline (Visit 3).
Receiving a low to moderate dose of an inhaled corticosteroid (equivalent to budesonide ≤ 800 μg per day) at a stable dose for at least 4 weeks before Visit 1.
Prescribed a short-acting inhaled bronchodilator as reliever therapy for relief of symptoms.
A peripheral blood eosinophil count ≥ 0.17 x 109/L at Visit 1.
Non-smoker or former smoker with a smoking history of ≤ 10 pack years who has not smoked for at least 6 months before screening (Visit 2) and has a negative urine cotinine at Visit 2.
Body mass index (BMI) ≥ 17 and ≤ 35 kg/m2.
Able to understand the nature of the study and comply with the protocol requirements, instructions and restrictions.
Able to provide signed and dated written informed consent to participate in the study. |
|
E.4 | Principal exclusion criteria |
Subjects who are pregnant or breast-feeding. Female subjects of childbearing potential who do not agree to use an adequate method of contraception and female subjects who do not provide a negative pregnancy test prior to receiving study drug.
Severe asthma exacerbation (defined as requiring treatment with oral or injectable corticosteroids, an emergency room visit or hospitalisation in the 4 weeks before Visit 1 or during the pre-treatment period).
Respiratory tract infection requiring treatment with antibiotics or a change in asthma therapy in the 4 weeks before Visit 1 or during the pre-treatment period.
A decrease in FEV1 and pre-bronchodilator PEF of at least 20% at baseline (Visit 3) when compared with the screening (Visit 2) values.
An increase in ACQ total score of 2.0 or more at baseline (Visit 3) when compared with the ACQ total score at screening (Visit 2).
Known cause of eosinophilia other than allergic airways disease.
Seasonal allergies that will necessitate introduction of intra-nasal corticosteroids during the study.
Oral β2 agonists, long-acting inhaled anticholinergics, LABAs, methylxanthines or cromones taken in the 4 weeks before randomisation (Visit 3) or leukotriene receptor antagonists or monoclonal antibody therapy 12 weeks before randomisation (Visit 3). Subjects who have
received allergen immunotherapy within the previous 12 months are not
eligible to participate in the study. Subjects who are taking oral beta blockers are not eligible to participate in the study.
Diagnosed with COPD or other relevant lung diseases (e.g., tuberculosis, bronchiolitis, α1-antitrypsin deficiency, interstitial lung disease, fibrosis, sarcoidosis, cystic fibrosis, bronchiectasis).
Abnormal and clinically significant safety laboratory values indicating an underlying unknown concomitant disease that requires further evaluation.
Subjects who, in the judgment of the investigator, have a clinically significant condition such as (but not limited to) cardiovascular, gastrointestinal, hepatic, renal, haematological, endocrine, metabolic, psychiatric or neurological disease that might compromise subject safety or compliance, interfere with evaluation, or preclude completion of the study.Subjects with malignant disease are excluded, unless they have had a primary cancer treated at least 10 years previously with no subsequent evidence of recurrence, or have a basal cell skin cancer only.
History of intolerance to leukotriene receptor antagonists.
History of lactose intolerance.
History of alcohol or substance abuse.
Has participated in a study with an investigational inhaled corticosteroid or a long acting bronchodilator (anti-cholinergic or beta 2 agonist) alone or in combination in the previous 4 weeks, has participated in a study with any other new molecular entity in the previous 12 weeks, has already been randomised into this study, or has an affiliation with either the Sponsor or the study centre. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Primary Endpoint for the Treatment Period
Change in trough (AM pre-dose and pre-reliever bronchodilator) FEV1 from
baseline (Visit 3) to Week 10 (Visit 6) for ADC3680 compared to placebo.
Nested Primary Endpoint for the Extension Period
Change in trough (AM pre-dose and pre-reliever bronchodilator) FEV1 from
Week 10 (Visit 6) to Week 12 (Visit 7) for montelukast added to ADC3680.
This endpoint will be considered only if the analysis of the primary endpoint
for the treatment period (above) is found to be significant. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Secondary endpoints for the Treatment period
Change in Asthma Control Questionnaire (ACQ) from baseline (Visit 3) to
Week 10 (Visit 6) for ADC3680 compared to placebo.
Change in trough pre-bronchodilator FEV1 from baseline (Visit 3) to Week 2
(Visit 4) for ADC3680 compared to placebo.
Change in trough pre-bronchodilator FEV1 from baseline (Visit 3) to Week 6
(Visit 5) for ADC3680 compared to placebo.
Change in trough pre-bronchodilator FEV1 % predicted from baseline (Visit 3)
to Week 2 (Visit 4) for ADC3680 compared to placebo.
Change in trough pre-bronchodilator FEV1 % predicted from baseline (Visit 3)
to Week 6 (Visit 5) for ADC3680 compared to placebo.
Change in trough pre-bronchodilator FEV1 % predicted from baseline (Visit 3)
to Week 10 (Visit 6) for ADC3680 compared to placebo.
Change in post-bronchodilator FEV1 from baseline (Visit 3) to Week 10 (Visit
6) for ADC3680 compared to placebo.
Change in pre-bronchodilator PEF (in-clinic) from baseline (Visit 3) to Week
2 (Visit 4) for ADC3680 compared to placebo.
Change in pre-bronchodilator PEF (in-clinic) from baseline (Visit 3) to Week
6 (Visit 5) for ADC3680 compared to placebo.
Change in pre-bronchodilator PEF (in-clinic) from baseline (Visit 3) to Week
10 (Visit 6) for ADC3680 compared to placebo.
Frequency of exacerbations during the treatment period for ADC3680
compared to placebo.
Change in blood eosinophils from baseline (Visit 3) to Week 10 (Visit 6) for
ADC3680 compared to placebo.
Change in serum IgE from baseline (Visit 3) to Week 10 (Visit 6) for
ADC3680 compared to placebo.
2.2.4 Secondary Endpoints for the Extension Period
Change in trough pre-bronchodilator FEV1 % predicted from extension
baseline (Week 10) to Week 12 (Visit 7) for ADC3680 plus montelukast.
Change in pre-bronchodilator PEF (in-clinic) from extension baseline (Week
10) to Week 12 (Visit 7) for ADC3680 plus montelukast.
Change in ACQ from extension baseline (Week 10) to Week 12 (Visit 7) for
ADC3680 plus montelukast.
Change in blood eosinophils from extension baseline (Week 10) to Week 12
(Visit 7) for ADC3680 plus montelukast. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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) | 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) | Yes |
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 | 75 |
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 |
Croatia |
Czech Republic |
Germany |
Hungary |
Poland |
United States |
|
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
|
LVLS (or last assessment for last subject in case of premature tearmination) |
|
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 | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |