A Study to Assess the Efficacy and Safety of HRG2005 Inhalation in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease

Study Overview
=================
Brief Summary
-----------------
This is a randomized, double blind, double dummy, active-controlled, parallel-group study to assess the efficacy and Safety of HRG2005 inhalation in patients with moderate to severe chronic obstructive pulmonary disease. Approximately 200 patients with moderate to severe COPD will be randomized into the study.

Official Title
-----------------
A Phase II, Randomized, Double Blind, Double Dummy, Active-controlled, Parallel-group Study to Assess the Efficacy and Safety of HRG2005 Inhalation in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease

Conditions
-----------------
Chronic Obstructive Pulmonary Disease

Intervention / Treatment
-----------------
* Drug: HRG2005 inhalation
* Drug: Placebo to match HRG2005 inhalation
* Drug: Placebo to match Indacaterol Maleate and Glycopyrronium Bromide Powder for inhalation
* Drug: Indacaterol Maleate and Glycopyrronium Bromide Powder for inhalation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Able and willing to provide written informed consent and to comply with the study protocol; Subjects 40 years of age or older (inclusive), Male or female subjects; Subjects with an established clinical history of COPD; A post-bronchodilator FEV1/FVC ratio must be <0.7 at Screening and FEV1 must be <80% and ≥30% predicted normal at pre-randomization; Tobacco Use: Current or former smokers with a history of at least 10 pack-years of cigarette smoking.; A score of ≥10 on the COPD Assessment Test (CAT) at pre-randomization. Exclusion Criteria: Subjects who required systemic corticosteroids or antibiotics or hospitalized due to poorly controlled COPD or who had lower respiratory tract infections that required antibiotics within 4 weeks prior to Screening to pre-randomization; Subjects who had respiratory tract infections that required antibiotics within 2 weeks prior to Screening; Subjects with other respiratory or respiratory related diseases, including but not limited to asthma, active tuberculosis, lung cancer, interstitial pulmonary disease, α1-antitrypsin deficiency, pulmonary heart disease, clinically significant pulmonary hypertension, clinically significant bronchiectasis, or other active pulmonary disease; Subjects with lung volume reduction surgery within the 12 months prior to Screening; Subjects who have Other known serious medical conditions； Subjects receiving oxygen therapy required for greater than 15 hours a day; Clinically significant electrocardiogram abnormality； Subjects with significant laboratory abnormality at screening； Suspected allergy to any ingredient in the study drug; Participation in clinical trials of any drug or medical device (except for screening failures) within 4 weeks before screening, or within 5 half-lives of the drug at screening (whichever is longer); Pregnant or lactating females; History of drug abuse, drinking within one year before screening Other conditions judged by the investigator to be not suitable to participate in the trial.

Ages Eligible for Study
-----------------
Minimum Age: 40 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a randomized, double blind, double dummy, active-controlled, parallel-group study.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group A<br>Drug1 dose 1+Drug 3 | Drug: HRG2005 inhalation<br>* Drug 1: dose 1; dose 2; dose 3<br>Drug: Placebo to match Indacaterol Maleate and Glycopyrronium Bromide Powder for inhalation<br>* Drug 3<br>|
| Experimental: Treatment group B<br>Drug1 dose 2+Drug 2+Drug 3 | Drug: HRG2005 inhalation<br>* Drug 1: dose 1; dose 2; dose 3<br>Drug: Placebo to match HRG2005 inhalation<br>* Drug 2<br>Drug: Placebo to match Indacaterol Maleate and Glycopyrronium Bromide Powder for inhalation<br>* Drug 3<br>|
| Experimental: Treatment group C<br>Drug1 dose 3+Drug 2+Drug 3 | Drug: HRG2005 inhalation<br>* Drug 1: dose 1; dose 2; dose 3<br>Drug: Placebo to match HRG2005 inhalation<br>* Drug 2<br>Drug: Placebo to match Indacaterol Maleate and Glycopyrronium Bromide Powder for inhalation<br>* Drug 3<br>|
| Other: Treatment group D<br>Drug 2+Drug 4 | Drug: Placebo to match HRG2005 inhalation<br>* Drug 2<br>Drug: Indacaterol Maleate and Glycopyrronium Bromide Powder for inhalation<br>* Drug 4<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in morning pre-dose trough FEV1 at week 12 |  | Up to week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in morning pre-dose trough FEV1 at each time point |  | up to week 48 | 
| Compared with the active-controlled group in morning pre-dose trough FEV1 at each time point |  | up to week 48 | 
| Proportion of subjects achieving an improvement from baseline≥100mL in morning pre-dose trough FEV1 |  | up to week 48 | 
| Peak change from baseline in FEV1 at week 12 |  | Up to week 12 | 
| FEV1 area under the curve from 0 to 12 hours (AUC0-12), 0 to 24 (AUC0-24) hours at Week 12 |  | Up to week 12 | 
| Rate of moderate or severe COPD exacerbations over 48 Weeks |  | up to week 48 | 
| Rate of severe COPD exacerbations over 48 Weeks |  | up to week 48 | 
| Change from baseline in CAT (COPD Assessment test) total score at each time point |  | up to week 48 | 
| Percentage of Days with No Rescue use and change from baseline in average daily rescue use at each time point |  | up to week 48 | 
| Incidence and severity of adverse events |  | Up to week 50 |