Revefenacin in Chinese Subjects With Moderate to Very Severe Chronic Obstructive Pulmonary Disease(COPD)

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).

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.

Study Overview

• Status: Completed
• Conditions: COPD
• Intervention / Treatment: Drug: Revefenacin 175 mcg in 3 ML Inhalation Solution; Drug: Placebo inhalation solution QD

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.

• Study Type: Interventional
• Enrollment (Actual): 258
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Dik WH Ng, PhD; Phone Number: +44 (0)1304 626895; Email: dik.ng@viatris.com

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230061
      • Anhui Medical University - Hefei First People's Hospital
  • Beijing
    • Beijing, Beijing, China, 100191
      • Peking University Third Hospital
    • Beijing, Beijing, China, 100730
      • Beijing Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510180
      • Guangzhou First People's Hospital
    • Guangzhou, Guangdong, China, 510260
      • The Second Affiliated Hospital of Guangzhou Medical University
    • Guangzhou, Guangdong, China, 510150
      • The Third Affiliated Hospital of Guangzhou Medical University
    • Guangzhou, Guangdong, China, 524000
      • Affiliated Hospital of Guangdong Medical University
  • Gunagdong
    • Guangzhou, Gunagdong, China, 510120
      • The First Affiliated Hospital of Guangzhou Medical University
  • Hainan
    • Haikou, Hainan, China, 570311
      • Hainan General Hospital
  • Hunan
    • Changsha, Hunan, China, 410005
      • The First Hospital of Changsha
  • Inner Mongolia
    • Baotou, Inner Mongolia, China, 014010
      • Inner Mongolia Baogang Hospital
    • Baotou, Inner Mongolia, China, 014017
      • The First Affiliated Hospital of Baotou Medical College - Respiration
    • Hohhot, Inner Mongolia, China, 10017
      • Inner Mongolia People's Hospital
    • Hohhot, Inner Mongolia, China, 10050
      • Affiliated Hospital of Inner Mongolia Medical College
  • Jiangsu
    • Jiangyin, Jiangsu, China, 214400
      • Jiangsu Jiangyin People's Hospital
    • Nanjing, Jiangsu, China, 211100
      • Nanjing Jiangning Hospital
    • Nanjing, Jiangsu, China, 210009
      • Zhongda Hospital, Southeast University - Pulmonology
    • Wuxi, Jiangsu, China, 214023
      • Wuxi People's Hospital
    • Yangzhou, Jiangsu, China, 225001
      • Yangzhou First People's Hospital
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • Jiangxi Provincial People's Hospital
    • Nanchang, Jiangxi, China, 330006
      • Nanchang University - The Second Affiliated Hospital
    • Pingxiang, Jiangxi, China, 337000
      • Jiangxi Pingxiang People's Hospital
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Bethune Hospital of Jilin University
    • Yanji, Jilin, China, 133000
      • Yanbian University Hospital
  • Liaoning
    • Shenyang, Liaoning, China, 110001
      • The First Hospital of China Medical University
    • Shenyang, Liaoning, China, 110004
      • Shengjing Hospital of China Medical University
  • Shanghai
    • Shanghai, Shanghai, China, 200031
      • Shanghai East Hospital
    • Shanghai, Shanghai, China, 201299
      • Shanghai Pudong New Area People's Hospital
  • Sichuan
    • Chengdu, Sichuan, China, 332001
      • Sichuan University - West China Hospital
  • Tianjin
    • Tianjin, Tianjin, China, 300052
      • Tianjin Medical University General Hospital - Respiration
    • Tianjin, Tianjin, China, 300192
      • The First Center Hospital of Tianjin
  • Xinjiang
    • Urumqi, Xinjiang, China, 830054
      • The First Affiliated Hospital of Xinjiang Medical University - Hospital
  • Zhejiang
    • Dongyang, Zhejiang, China, 322199
      • Dongyang People's Hospital
    • Hangzhou, Zhejiang, China, 310005
      • Xinhua Hostipal of Zhejiang Province
    • Huzhou, Zhejiang, China, 313003
      • Huzhou Central Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Revefenacin inhalation solution 175 mcg QD.	Drug: Revefenacin 175 mcg in 3 ML Inhalation Solution; Revefenacin
Placebo Comparator: Placebo inhalation solution QD.	Drug: Placebo inhalation solution QD; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Trough FEV1 on Day 85	Change from Baseline (Day 1, pre-dose) trough FEV1 on Day 85	up to 12 weeks

Collaborators and Investigators

• Sponsor: Mylan Pharma UK Ltd.
• Investigators: Study Director: Dik WH Ng, PhD, Mylan Pharmaceuticals Inc

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2021
• Primary Completion (Actual): July 26, 2023
• Study Completion (Actual): July 26, 2023

Study Registration Dates

• First Submitted: September 7, 2021
• First Submitted That Met QC Criteria: September 7, 2021
• First Posted (Actual): September 16, 2021

Study Record Updates

• Last Update Posted (Actual): August 18, 2023
• Last Update Submitted That Met QC Criteria: August 16, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Revefenacin; Long-acting muscarinic receptor antagonist(LAMA)
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Chronic Disease; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Pharmaceutical Solutions
• Other Study ID Numbers: REV-3001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No