# A Multicenter Randomized, Double-blind, Phase 2, Placebo Controlled Study to Determine the Safety and Efficacy of Ivacaftor (VX-770) for the Treatment of Chronic Obstructive Pulmonary Disease

> **NIH NIH P30** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $350,188

## Abstract

New therapies are needed for the treatment of chronic obstructive pulmonary disease (COPD), 
which accounts for over $40 billion in annual healthcare costs, is the 3rd leading cause of death 
in the U.S., and is major source of health disparity, being over-represented in the Deep South. 
Like cystic fibrosis (CF), COPD is characterized by mucus obstruction that is associated with 
accelerated loss of lung function and excess mortality. Cigarette smoke exhibits a variety of 
deleterious effects on airway epithelial function in vitro and in vivo and our preliminary data 
indicates it also causes a significant reduction in CFTR activity that leads to a pronounced 
decrement in mucociliary transport. Furthermore, CFTR dysfunction is independently associated 
with chronic bronchitis and dyspnea, can persist despite smoking cessation, and can be 
reversed by the CFTR potentiator ivacaftor in vitro and in vivo by activating wild-type CFTR, 
resulting in a robust increase in mucociliary transport. Combined with unprecedented clinical 
improvement via augmented mucociliary clearance observed in CF patients with a responsive 
CFTR mutation treated with ivacaftor, these data indicate that CFTR represents a viable 
therapeutic target to address mucus stasis in COPD patients with chronic bronchitis (potentially 
representing over 8 million patients in the U.S. alone). In this project, we will investigate the 
hypothesis that ivacaftor can augment CFTR activity in individuals with COPD who exhibit 
chronic bronchitis. Though our preliminary data are compelling, questions regarding the most 
informative and responsive endpoints and dose selection mandate the studies outlined in this 
application. To address this, we have designed an innovative Phase 2, Randomized, Double- 
blind, Placebo Controlled Pilot Trial to Determine the Safety and Efficacy of Ivacaftor (VX-770) 
for the Treatment of Chronic Obstructive Pulmonary Disease (The Multicenter TOPIC study), 
and will address a number of key questions to the field of COPD and airway epithelial biology 
using the latest methods for assessing CFTR activity, epithelial function, mucociliary clearance, 
and clinical outcomes. The TOPIC study will test whether MCC can be augmented in COPD 
patients with chronic bronchitis, ameliorating human disease even in the absence of congenital 
mutations in the CFTR gene. The trial will provide an initial proof of concept evaluating the 
efficacy of CFTR potentiators in COPD, and we will also examine differential effects based on 
race/ethnicity, socio-economic status, and smoking status. If successful, the results could 
establish a novel treatment paradigm to address mucus dysfunction in COPD, an important 
cause of morbidity that is independently associated with mortality and disease progression.

## Key facts

- **NIH application ID:** 10018505
- **Project number:** 5P30DK072482-14
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** MARK T DRANSFIELD
- **Activity code:** P30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $350,188
- **Award type:** 5
- **Project period:** 2007-04-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10018505

## Citation

> US National Institutes of Health, RePORTER application 10018505, A Multicenter Randomized, Double-blind, Phase 2, Placebo Controlled Study to Determine the Safety and Efficacy of Ivacaftor (VX-770) for the Treatment of Chronic Obstructive Pulmonary Disease (5P30DK072482-14). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10018505. Licensed CC0.

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