| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Inadequately Controlled Asthma |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10003553 |
| E.1.2 | Term | Asthma |
|
| 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 853 is effective compared with placebo as measured by change in Asthma Control Questionnaire (ACQ) symptom scores from
baseline to week 12.
|
|
| E.2.2 | Secondary objectives of the trial |
Evaluate the efficacy of AMG 853 as measured by:
• Pre- and post-bronchodilator forced expiratory volume in 1 second (FEV1),
• AM and PM peak expiratory flow rate (PEFR),
• Use of rescue short-acting β-agonist (SABA),
• Daily symptom score (aggregate/night and individual symptoms; and symptom free
days),
• Asthma quality of life questionnaire (AQLQ).
Exploratory Objectives:
Evaluate the efficacy of AMG 853 as measured by:
• Asthma exacerbations,
• Patient global rating of change,
• Total serum Immunoglobulin E (IgE),
• Exhaled nitric oxide,
• Sputum eosinophils (substudy),
• Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ),
• Sleep scale from Medical Outcomes Study (Sleep-MOS).
Assess the pharmacokinetics of AMG 853.
Investigate novel circulating biomarkers in the asthma setting.
Safety Objectives:
Evaluate the safety of AMG 853 as measured by:
• Adverse events,
• Changes in electrocardiogram (ECG),
• Laboratory profiles,
• Vital signs.
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Males or females 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 prior to screening. The ICS dose is expected
to remain the same from screening through the end of study.
Ongoing asthma symptoms with ACQ 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
Signed the IRB-approved informed consent before any study-specific procedure |
|
| E.4 | Principal exclusion criteria |
Acute asthma exacerbation requiring emergency room treatment or
hospitalization within 2 months of screening
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, 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 two separate occasions during the screening period)
Known malabsorption syndromes (eg, active duodenal ulceration, inflammatory
bowel disease; history of small intestine surgery that involved resection or history
of gastric bypass)
Respiratory infection within 4 weeks of screening visit
Any evidence of active infection at screening visit requiring systemic antibiotics
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 malignancy occurred > 5 years ago, subject is eligible with
documentation of disease-free state since treatment)
Systemic corticosteroids within 6 weeks before screening visit
Received long-acting β-agonist, theophylline, inhaled anticholinergics, oral β-2
agonists, or cromolyn therapeutics within 1 week of first run-in visit
Leukotriene antagonists within 2 weeks before first run-in visit
5-lipoxygenase inhibitors for asthma (eg, Zyflo®) within 1 week before first run-in
visit
Previous receipt of AMG 853
Current receipt of any experimental or commercial biologic agent at screening
Xolair® within 2 months before screening visit
Known positive tuberculin skin test or recent (within 6 months) exposure to a
person with active tuberculosis.
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 chest x-ray in the past year, and have no symptoms per the
tuberculosis worksheet.
Known to have tested positive for hepatitis B surface antigen, hepatitis C virus,
human immunodeficiency virus
Elevated AST/ALT ≥ 1.5 x the upper limit of normal at screening
Creatinine clearance < 50 mL/min (based on the Cockroft-Gault formula,
calculated by the central laboratory)
Bilirubin ≥ 1.5 x the upper limit of normal at screening
Laboratory abnormality, which, in the opinion of the investigator, will prevent the
subject from completing the study or will interfere with the interpretation of the
study results
Subject is pregnant or breast feeding
Subject is not willing to use highly effective birth control for the duration of the
study including the 2-week follow-up period for women (except women at least
2 years post menopausal or surgically sterile) and for up to 10 weeks after the
last dose for men (except men whose female partners are at least 2 years post
menopausal or surgically sterile).
Highly effective methods of birth control are those which result in a low failure
rate when used consistently and correctly such as implants, injectables,
combined oral contraceptives, some intrauterine devices (IUDs), sexual
abstinence or vasectomised partner. It is the responsibility of the physician and
subject to decide together on the choice of an appropriate birth control method.
Subject currently is enrolled in or has not yet completed at least 30 days since
ending other investigational device or drug study(s), or subject is receiving other
investigational agent(s)
Other investigational procedures are excluded
Any planned surgery (eg, elective cosmetic surgery) during the course of this
study
Subject will not be available for follow-up assessments
Presence of any condition that could, in the opinion of the investigator,
compromise the subject’s ability to participate in the study, such as history of
substance abuse, alcoholism, or a psychiatric condition |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Efficacy Endpoint:
• Change in ACQ scores from baseline to week 12
|
|
| 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 | 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.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
| 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 | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 34 |
| 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 | Information not present in EudraCT |
| 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 |
|
| 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
|
| The end of study is defined as the last visit of the last subject on the study. |
|
| 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 | 2 |
| 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 | 2 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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