Clinical trial NCT05046795: Revefenacin in Chinese Subjects With Moderate to Very Severe Chronic Obstructive Pulmonary Disease(COPD)
Official title: A Randomized, Double Blind, Placebo-Controlled, Parallel Group Study of Nebulized Revefenacin Inhalation Solution in Chinese Subjects With Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: COPD
Keywords: Revefenacin
Long-acting muscarinic receptor antagonist(LAMA)
Lead sponsor: Viatris Inc.
Sponsor class: INDUSTRY
First posted: 2021-09-16
Enrollment: 258
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicenter, randomized, double-blind, placebo-control, parallel group study
Primary purpose: TREATMENT

Brief summary: This study is a phase III clinical study to assess the efficacy and safety of Revefenacin inhalation solution 175 mcg administered once daily via nebulization for 12 weeks compared to placebo in a population of Chinese subjects with moderate to very severe COPD.

Detailed description: This will be a multi-center, randomized, double blind, placebo-controlled, parallel group study, randomizing approximately 320 male or female moderate-very severe COPD subjects. Subjects will receive study drug for 12 weeks. Treatments to be received during the study will include one of the following, administered using a centrally-provided, standard jet nebulizer and compressor via a mouthpiece: A. Revefenacin inhalation solution 175 mcg Quaque die (QD). B. Placebo inhalation solution QD. Subjects will have approximately 6 clinic visits (encompassing a screening period of up to 30 days and a treatment period of 12 weeks), and a follow-up telephone call 1-2 weeks after the End of Treatment (EoT) visit.

Eligibility criteria: Inclusion Criteria:

* Key inclusion criteria include:

  * Males and females of Chinese ethnicity, at least 40 years of age. Females may be of either childbearing or non-childbearing potential. All females of childbearing potential must be using an acceptable, highly effective method of contraception and have a negative pregnancy test at screening.
  * A clinical diagnosis for at least 6 months prior to screening of COPD according to Global Initiative for Chronic Obstructive Lung Disease(GOLD) guidelines.
  * Subject is capable of performing reproducible spirometry maneuvers as described by current American Thoracic Society/European Respiratory Society (ATS/ERS) Guidelines and has a post-ipratropium (500 mcg nebulized) Forced Expiratory Volume in

    1 second(FEV1)/Forced Vital Capacity(FVC) ratio \<0.7 at Visit 2.
  * Subject has moderate to very severe COPD with a post-ipratropium (500 mcg nebulized) FEV1 less than 80% of predicted normal (using the Global Lung Function Initiative reference range; ) and an absolute FEV1 \>700 mL at Visit 2
  * Current smoker or ex-smoker, with a history of at least 10 pack-years of tobacco smoking. Ex-smokers must have stopped smoking \>6 months prior to Visit 1.

Exclusion Criteria:

* Key exclusion criteria include:

  * Previously dosed with Revefenacin.
  * Current diagnosis of asthma.
  * Alpha-1 anti-trypsin deficiency.
  * Other chronic or active respiratory disorder (e.g., clinically significant \[as determined by the Investigator\] bronchiectasis, pulmonary fibrosis, sarcoidosis, pneumoconiosis, active tuberculosis).
  * Symptoms of, or treatment for an Acute Exacerbation of COPD(AECOPD) requiring antibiotics and/or oral/systemic corticosteroids or in-patient hospitalization during the 28 days preceding screening or during the screening period between Visit 1 and Visit 3.
  * Pneumonia requiring hospitalization within 28 days prior to screening or during the screening period between Visit 1 and Visit 3.
  * Lower respiratory tract infection requiring treatment with antibiotics during the 28 days preceding screening or during the screening period between Visit 1 and Visit 3.
  * History or presence of pulmonary hypertension, respiratory failure, cor pulmonale or right ventricular failure which may impact the safety of the subject in the clinical judgement of the Investigator.
  * History of pulmonary lobectomy, lung volume reduction surgery, or lung transplantation.
  * Use of supplemental oxygen therapy for more than 15 hours per day (includes night-time use).
  * Subjects with hepatic impairment.
  * Subject suffers from any medical condition that would preclude the use of inhaled anticholinergics, including narrow-angle glaucoma, symptomatic benign prostatic hyperplasia, bladder neck obstruction, or urinary retention.
  * Subjects who are unable to stop any of the following medications, and refrain from their use throughout the study until the final dose of study drug:

    * Short-acting β2 agonists (except study-supplied salbutamol).
    * Short-acting anticholinergic agents (except those used for reversibility testing).
    * Long-acting anticholinergics (except study supplied medication).
    * Combination β2 agonists/anticholinergic agents.
    * Combination β2 agonists/inhaled corticosteroids/anticholinergic agents.
    * Phosphodiesterase 4 inhibitors.
    * Theophyllines.
    * Leukotriene inhibitors.
    * Orally inhaled nedocromil or cromolyn sodium.
    * Oral or parenteral corticosteroids.

Primary outcomes:
measure: Trough FEV1 on Day 85
timeFrame: Baseline and Day 85
measure: Trough FEV1 on Day 85 - Sensitivity Analysis With Missing Data Imputed
timeFrame: Baseline, Day 29, Day 57 and Day 85
Secondary outcomes:
measure: Trough FVC on Day 85
timeFrame: Baseline and Day 85
measure: Change From Baseline in Peak FEV1 (0-2h) on Day 1
timeFrame: Day 1, from 45 minutes before dosing to 2 hours after dosing
measure: Change From Baseline in Peak FEV1 (0-2h) on Day 85
timeFrame: Day 1 (baseline) and Day 85, from 45 minutes before dosing to 2 hours after dosing
measure: Change From Baseline in SGRQ Total Score on Day 85
timeFrame: Day 1 (baseline) and Day 85
measure: Number (%) of SGRQ Responders on Day 85
timeFrame: Day 85
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Medical University - Hefei First People's Hospital
state: Anhui
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Hospital
state: Beijing
city: Guangzhou
country: China
facility: The Third Affiliated Hospital Of Guangzhou Medical University
state: Guangdong
city: Guangzhou
country: China
facility: Guangzhou First People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: The Second Affiliated Hospital Of Guangzhou Medical University
state: Guangdong
city: Guangzhou
country: China
facility: Affiliated Hospital of Guangdong Medical University
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou Medical University
state: Gunagdong
city: Haikou
country: China
facility: Hainan General Hospital
state: Hainan
city: Changsha
country: China
facility: The First Hospital of Changsha
state: Hunan
city: Baotou
country: China
facility: Inner Mongolia Baogang Hospital
state: Inner Mongolia
city: Baotou
country: China
facility: The First Affiliated Hospital of Baotou Medical College - Respiration
state: Inner Mongolia
city: Hohhot
country: China
facility: Inner Mongolia People's Hospital
state: Inner Mongolia
city: Hohhot
country: China
facility: Affiliated Hospital of Inner Mongolia Medical College
state: Inner Mongolia
city: Jiangyin
country: China
facility: Jiangsu Jiangyin People's Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Zhongda Hospital, Southeast University - Pulmonology
state: Jiangsu
city: Nanjing
country: China
facility: Nanjing Jiangning Hospital
state: Jiangsu
city: Wuxi
country: China
facility: Wuxi People's Hospital
state: Jiangsu
city: Yangzhou
country: China
facility: Yangzhou First People's Hospital
state: Jiangsu
city: Nanchang
country: China
facility: Jiangxi Provincial People's Hospital
state: Jiangxi
city: Nanchang
country: China
facility: Nanchang University - The Second Affiliated Hospital
state: Jiangxi
city: Pingxiang
country: China
facility: Jiangxi Pingxiang People's Hospital
state: Jiangxi
city: Changchun
country: China
facility: The First Bethune Hospital of Jilin University
state: Jilin
city: Yanji
country: China
facility: Yanbian university hospital
state: Jilin
city: Shenyang
country: China
facility: The First Hospital of China Medical University
state: Liaoning
city: Shenyang
country: China
facility: Shengjing Hospital of China Medical University
state: Liaoning
city: Shanghai
country: China
facility: Shanghai East Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Pudong New Area People's Hospital
state: Shanghai
city: Chengdu
country: China
facility: Sichuan University - West China Hospital
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital - Respiration
state: Tianjin
city: Tianjin
country: China
facility: The First Center hospital of Tianjin
state: Tianjin
city: Urumqi
country: China
facility: The First Affiliated Hospital of Xinjiang Medical University - Hospital
state: Xinjiang
city: Dongyang
country: China
facility: Dongyang People's Hospital
state: Zhejiang
city: Hangzhou
country: China
facility: Xinhua Hostipal of Zhejiang Province
state: Zhejiang
city: Huzhou
country: China
facility: Huzhou Central Hospital
state: Zhejiang
Study officials:
affiliation: Mylan Pharmaceuticals Inc
name: Dik WH Ng, PhD
role: STUDY_DIRECTOR
References: