Effect of Switching From Cigarette Smoking to THS on Disease Progression in Mild to Moderate COPD Subjects With Chronic Bronchitis Symptoms.

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate the slowing of the disease progression including the improvement of Chronic Obstructive Pulmonary Disease (COPD) symptoms in smoking subjects with mild to moderate COPD and a history of chronic bronchitis symptoms (sputum and cough) who switch to the Tobacco Heating System (THS) as compared to those who continue to smoke cigarettes.

Detailed Description
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This study will be a multiregional (Europe, U.S., and Asia) multi-center, open-label study with 3-group, parallel preference design (Cigarette, THS use, and Smoking Abstinence). Subjects will self-select their group allocation according to their preference. Subjects who would like to quit cigarettes or THS during the study will be encouraged to do so and will be referred to appropriate services. The study will be declared successful if a slowing of the disease progression is demonstrated with the primary objective endpoint of forced expiratory volume in the first second (FEV1) post-bronchodilator at Month 36 or if an improvement of COPD symptoms (COPD Assessment Test total score at interim analysis at Month 12) is demonstrated.

Official Title
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A 3-year, 3-group, Preference, Multi-center Study to Demonstrate the Slowing of Disease Progression When Switching From Cigarette Smoking to the Tobacco Heating System (THS) in Mild to Moderate Chronic Obstructive Pulmonary Disease (COPD) Subjects With a History of Chronic Bronchitis Symptoms.

Conditions
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COPD, Smoking, Tobacco Use

Intervention / Treatment
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* Other: THS use
* Other: Cigarette
* Other: Smoking Abstinence


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Subjects have read, understood, and signed the written informed consent form (ICF) Diagnosis of COPD GOLD Stage 1 or 2 (FEV1/FVC <0.7 & FEV1 ≥60% predicted [post-BD]) History of chronic bronchitis symptoms (sputum and cough) over the previous 12 months assessed by CAT1 and CAT2 scores ≥ 3 Body mass index (BMI) 17.6-40.0 kg/m2 and body weight > 50 kg (male) or 40 kg (female). Subject has a smoking history of at least 10 years. Subject has been smoking ≥ 10 commercially available cigarettes/day on average (no brand restriction) for at least 1 year prior to V1 (based on self-reporting). Subject has not used other tobacco and nicotine products apart from cigarettes on a daily basis over the past year prior to V1. For subjects not willing to quit smoking only: have been advised to quit smoking, informed of smoking risks and of cessation programs and is still not willing to quit during the study duration. Subjects willing to quit smoking only: willing to set a target quit date (TQD) within the next 28 days at V1 as assessed by self-reported questions. Main Exclusion Criteria: Subjects with any (mild, moderate or severe) COPD exacerbation that has not resolved at least four weeks prior to V1 Subjects with other relevant pulmonary diseases than COPD. No new examination is required if the subject can present at V1, a Chest X-Ray (CXR) not older than 6 months with anterior-posterior and left lateral views Subjects with pneumonia or other lower respiratory tract infections that have not resolved at least four weeks prior to V1 Subjects with other active systemic infections that have not resolved at least 4 weeks prior to V1 Subjects with other active respiratory disorders: tuberculosis, lung cancer, bronchiectasis, sarcoidosis, asthma, pulmonary hypertension, interstitial lung diseases (e.g., idiopathic pulmonary fibrosis [IPF]), or other active pulmonary diseases during the screening period (V1 to V2) The subject is confirmed or suspected with active SARS-CoV-2 infection (as per site and per country recommendation) Clinically significant ECG alterations that will not allow subject to participate in the study, per Investigator's discretion Any concomitant disease that in the opinion of the investigator would interfere with the study procedures Subjects with diagnosed alpha-1 antitrypsin deficiency (AATD) History of alcohol and / or drug abuse (other than tetrahydrocannabinol [THC]). Positive serology test (HIV 1/2, hepatitis B or C). Inability to cooperate with the study procedures Previous participation in this study, or participation in an investigational study (drug or medical device) within 4 weeks before V1 (participation in observational studies/registries allowed) Close affiliation with the investigational site: a close relative of the investigator, a person dependent on the investigational site (e.g., employee or student of the investigational site) Subject is a current or former employee of the tobacco industry or their first-degree relatives (parent, child, spouse) Subjects have re-initiated smoking in the six months prior to V1 Subjects have used in the past 3 months, or are currently daily using THS Any oral or injectable corticosteroids (acute or chronic treatments) in the 2 months preceding V1, excluding short term use for a COPD exacerbation. Female subject is pregnant or breastfeeding, (a urine pregnancy test will be performed at V1 and V2) For women of childbearing potential, female subject who does not agree to using an acceptable method of effective contraception during the entire study.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A multiregional (Europe, U.S. and Asia) multi-center, open-label study with 3-group, parallel preference design (Cigarette, THS use and Smoking Abstinence).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: THS<br>Subjects who are not willing to quit smoking. | Other: THS use<br>* Subjects who are not willing to quit smoking during the study duration will switch from cigarettes to using THS<br>* Other names: Tobacco Heating System 3.0;|
| Active Comparator: Cigarette<br>Subjects who are not willing to quit smoking. | Other: Cigarette<br>* Subjects who are not willing to quit smoking during the study duration will continue smoking their own preferred brand of commercially available cigarettes.<br>|
| Active Comparator: Smoking Abstinence<br>Subjects who are willing to quit smoking. | Other: Smoking Abstinence<br>* Subjects who are willing to quit smoking may be prescribed an NRT to support them in remaining abstinent from use of any tobacco and nicotine containing products during the study. (Behavioral support will be provided to subjects to aid with abstinence.)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Progression | Disease progression will be assessed by measuring Forced Expiratory Volume in 1 second (FEV1), post-bronchodilator | At month 36 | 
| COPD symptoms | COPD symptoms will be assessed from the total score of the COPD Assessment Test (CAT). | At month 12 |