E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Asthma:
Subjects with chronic inflammatory disorder of the airways characterized by recurrent episodes of wheezing, breathlessness, chest tightness, and coughing resulting from abnormal airflow obstruction and constriction |
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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 | 13.1 |
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 |
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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 |
The primary objective is to determine if AMG 827 is effective compared to placebo as
measured by change in Asthma Control Questionnaire (ACQ) composite scores from baseline to week 12 |
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E.2.2 | Secondary objectives of the trial |
Evaluate the efficacy of AMG 827 as measured by:
• Pre- and post-bronchodilator FEV1 (forced expiratory volume in 1 second),
• AM and PM peak expiratory flow rate (PEFR),
• Use of rescue short-acting β-agonist,
• Daily symptoms (aggregate/night and individual symptoms; and symptom-free days)
• Asthma quality life of questionnaire (AQLQ).
Evaluate the pharmacokinetics of AMG 827 |
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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 |
Pharmacokinetic Sampling Sub-study:
Approximately 60 subjects (about 15 subjects per treatment arm) will participate in the pharmacokinetic sub-study. Subjects in the pharmacokinetic sub-study will be required to visit the study site for additional blood draws. For these subjects, additional pharmacokinetic assessments to collect AMG 827 PK data will include a 5 mL PK sample within the specified time window during weeks 1 and 8 (1 additional visit during week 1 and 2 additional visits during week 8).
Biomarker Development Sub-study:
Participation in the biomarker development sub-study is optional. Biomarkers are objectively measured and evaluated indicators of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.
Pharmacogenetic Sub-study:
Participation in the pharmacogenetic sub-study is optional. DNA will be used to analyze genetic markers for specific known components related to the IL-17 pathway or asthma and to support broader investigation of genetic aspects of AMG 827 and its role in autoimmune and inflammatory disease.
Sputum Sub-study:
Approximately 100 subjects will participate in the induced sputum sub-study.
Subjects participating in the sub-study will be required to undergo induced sputum collection at baseline and week 12. |
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E.3 | Principal inclusion criteria |
- Men or women 18 to 65 years of age at the time of screening
- Percent of predicted FEV1 ≥ 50% and ≤ 80% at screening and baseline visits
- At least 12% reversibility over pre-bronchodilator FEV1 with SABA
inhalation (up to 8 puffs) or nebulized equivalent (up to 2 treatments with
2.5 mg albuterol), demonstrated in the office during screening
- Inhaled corticosteroid (ICS) ≥ 200 and ≤ 1000 μg/day fluticasone or
equivalent. Stable ICS dose for ≥ 30 days before screening and must
have used ICS for at least the last 3 consecutive months before
screening. The ICS dose is expected to remain the same from screening
through the end of study.
- Ongoing asthma symptoms with ACQ composite score ≥ 1.5 points at
screening and baseline
- If receiving allergen immunotherapy, a stable dose for > 3 months before
screening and anticipated to remain stable for the duration of the study
- Nonsmoker or ex-smoker with < 10 pack-years (eg, 1 pack per day for 10
years) who stopped ≥ 1 year ago
- Subject has a negative purified protein derivative (tuberculin) skin test
within 6 weeks prior to randomization and has not been exposed to a
person with active tuberculosis within 6 months of screening. Subjects
with a known positive tuberculin skin test are allowed if:
• They have completed treatment with appropriate chemoprophylaxis,
or
• They have a history of Bacillus Calmette-Guerin vaccination with a
negative Quantiferon test
- Subject or subject’s legally acceptable representative has provided
informed consent, before any study specific procedure |
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E.4 | Principal exclusion criteria |
- Acute asthma exacerbation requiring emergency room treatment or
hospitalization within 2 months of screening or any exacerbation between
screening and baseline
- Respiratory infection within 4 weeks of screening visit or 1 week of
baseline visit
- Any evidence of active infection at screening, during the run-in period or
at the baseline visit requiring systemic antibiotics
- History of endotracheal intubation for asthma-related exacerbation within
3 years of screening
- History of chronic obstructive pulmonary disease or other chronic
pulmonary condition other than asthma
- Current diagnosis of sleep apnea with ongoing symptoms or requiring
continuous positive airway pressure
- History of aspirin-sensitive asthma
- Any uncontrolled or clinically significant systemic disease (eg,
uncontrolled diabetes, liver disease)
- Any finding on the screening ECG that in the opinion of the investigator
requires further cardiovascular evaluation
- Poorly controlled hypertension defined as resting blood pressure
> 150/90 mmHg (assessed on 2 separate occasions during the screening
period)
- Malignancy (other than resected cutaneous basal or cutaneous squamous
cell carcinoma, or treated in situ cervical cancer considered cured) within
5 years of screening visit (if a malignancy occurred > 5 years ago, subject
is eligible with documentation of disease-free state since treatment)
- Known to have tested positive for hepatitis B virus surface antigen,
hepatitis C virus antibody or human immunodeficiency virus
- Subject is pregnant or breast feeding, or planning to become pregnant while enrolled in the study, or up to 10 weeks after the last dose of study drug. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in ACQ composite scores from baseline to week 12 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary endpoint, the change from baseline in ACQ composite score at week 12, will be tested for a linear trend of treatment effect (placebo, 140 mg, 210 mg and 280 mg QOW) |
|
E.5.2 | Secondary end point(s) |
Secondary endpoints
• Change in FEV1 pre- and post-bronchodilator treatment from baseline to week 12
• Change in am and pm PEFR from baseline to week 12
• Change in frequency of rescue SABA use from baseline to week 12
• Change in daily asthma symptoms (aggregate/night and individual) from baseline to week 12
• Change in AQLQ score from baseline to week 12
• Proportion of symptom-free days from baseline to week 12
• Pharmacokinetic measures |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
The secondary endpoint of FEV1, will be analyzed for both the change in absolute FEV1 as well as the change in percent of predicted FEV1 at week 12. |
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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 | No |
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 | 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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 5 |
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 | 32 |
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 |
Austria |
Finland |
Hungary |
Korea, Republic of |
Netherlands |
Poland |
Russian Federation |
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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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The last clinical planned event for protocol-specified assessments supporting all planned analyses of the study |
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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 | |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 14 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 14 |