A Study to Evaluate the Dosing of AMG 827 for Subjects With Inadequately Controlled Asthma
- Conditions
- 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 constrictionMedDRA version: 13.1Level: PTClassification code 10003553Term: AsthmaSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disordersTherapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2010-019543-19-HU
- Lead Sponsor
- Amgen Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 300
- 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 300
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
- 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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective is to determine if AMG 827 is effective compared to placebo as<br>measured by change in Asthma Control Questionnaire (ACQ) composite scores from baseline to week 12;Secondary Objective: Evaluate the efficacy of AMG 827 as measured by:<br>• Pre- and post-bronchodilator FEV1 (forced expiratory volume in 1 second),<br>• AM and PM peak expiratory flow rate (PEFR),<br>• Use of rescue short-acting ß-agonist,<br>• Daily symptoms (aggregate/night and individual symptoms; and symptom-free days)<br>• Asthma quality life of questionnaire (AQLQ).<br>Evaluate the pharmacokinetics of AMG 827;Primary end point(s): Change in ACQ composite scores from baseline to week 12;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)
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Secondary endpoints<br>• Change in FEV1 pre- and post-bronchodilator treatment from baseline to week 12<br>• Change in am and pm PEFR from baseline to week 12<br>• Change in frequency of rescue SABA use from baseline to week 12<br>• Change in daily asthma symptoms (aggregate/night and individual) from baseline to week 12<br>• Change in AQLQ score from baseline to week 12<br>• Proportion of symptom-free days from baseline to week 12<br>• Pharmacokinetic measures;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.