Lead Investigator: Margaret Salisbury, Vanderbilt University Medical Center
Title of Proposal Research: Defining the physiologic trajectory of presymptomatic through advanced pulmonary fibrosis
Vivli Data Request: 7543
Funding Source: This data application precedes an application for funding from the NIH/NHLBI which will fund personnel effort and other aspects of the research. The requested data will be used to externally-validate a statistical model that is developed using several other natural history cohorts available to the research team.
Potential Conflicts of Interest: None
Summary of the Proposed Research:
Pulmonary fibrosis (PF) results in irreversible and progressive scarring of the lung. Symptoms of progressive cough and shortness of breath may precede diagnosis by several years, and the life expectancy following diagnosis is 3-5 years on average. PF affects approximately 200,000 persons in the USA, and the prevalence may be increasing. Despite decades of research, only two disease-modifying therapies are available for PF, with no prevention strategies elucidated. Development of disease modifying treatment for PF hinges on measuring treatment effect on the change in forced vital capacity (FVC), a key physiologic surrogate of PF progression. The FVC is the total amount of air a person can forcibly exhale after the deepest inhalation possible; the amount decreases as PF worsens over time. Use of change in FVC as primary trial endpoint is limited by the variable rate of change across the disease lifespan, with attenuated magnitude of change in the earliest (pre-symptomatic) stage of the disease. Trials have employed enrichment design (enrolling likely progressors) and still randomized hundreds to detect a treatment effect. In rare and slowly progressive neurologic diseases, repeated measures models have synthesized natural history data to describe the longitudinal decay in multiple relevant parameters simultaneously as a function of a disease age variable. Measuring the proportional treatment effect on the model-based disease decay parameter improves trial power over any single parameter. Summarization of the sequenced decay of multiple physiologic parameters using this novel, powerful methodology has not been evaluated in PF, where a key barrier to expediting therapeutic development is an incomplete understanding of the sequence and magnitude of change in physiologic parameters across the complete disease natural history. Capitalizing on the maturity of our ongoing natural history cohort of asymptomatic relatives at risk for familial PF (fPF) who are screened longitudinally (via high-resolution computed tomography scan [HRCT]) of the lungs for early, progressive PF, we propose to develop such a model. This information can be used to design a better way to measure the effect of treatment on lung function in patients at all stages of disease and will enable design of prevention trials.
Requested Studies:
A Randomized, Double-Blind, Placebo Controlled, Phase 3 Study of the Efficacy and Safety of Pirfenidone in Patients With Idiopathic Pulmonary Fibrosis (ASCEND Trial)
Data Contributor: Roche
Study ID: NCT01366209
Sponsor ID: PIPF-016
A Randomized, Double-Blind, Placebo Controlled, Phase 3 Study of the Safety and Efficacy of Pirfenidone in Patients With Idiopathic Pulmonary Fibrosis
Data Contributor: Roche
Study ID: NCT00287729
Sponsor ID: PIPF-006
A Double Blind, Randomized, Placebo-controlled Trial Evaluating the Efficacy and Safety of Nintedanib Over 52 Weeks in Patients With Progressive Fibrosing Interstitial Lung Disease (PF-ILD)
Data Contributor: Boehringer Ingelheim
Study ID: NCT02999178
Sponsor ID: 1199.247
(Note: Additional studies added to the request 20-Sep-2023)
A Randomized, Double-Blind, Placebo Controlled, Phase 3, Three-Arm Study of the Safety and Efficacy of Pirfenidone in Patients With Idiopathic Pulmonary Fibrosis
Data Contributor: Roche
Study ID: NCT00287716
Sponsor ID: PIPF-004
A 52 Weeks, Double Blind, Randomized, Placebo-controlled Trial Evaluating the Effect of Oral BIBF 1120, 150 mg Twice Daily, on Annual Forced Vital Capacity Decline, in Patients With Idiopathic Pulmonary Fibrosis (IPF)
Data Contributor: Boehringer Ingelheim
Study ID: NCT01335464
Sponsor ID: 1199.32
A 52 Weeks, Double Blind, Randomized, Placebo-controlled Trial Evaluating the Effect of Oral BIBF 1120, 150 mg Twice Daily, on Annual Forced Vital Capacity Decline, in Patients With Idiopathic Pulmonary Fibrosis (IPF)
Data Contributor: Boehringer Ingelheim
Study ID: NCT01335477
Sponsor ID: 1199.34
A 12-week, Double Blind, Randomised, Placebo Controlled, Parallel Group Trial Followed by a Single Active Arm Phase of 40 Weeks Evaluating the Effect of Oral Nintedanib 150 mg Twice Daily on Change in Biomarkers of Extracellular Matrix (ECM) Turnover in Patients With Idiopathic Pulmonary Fibrosis (IPF) and Limited Forced Vital Capacity (FVC) Impairment.
Data Contributor: Boehringer Ingelheim
Study ID: NCT02788474
Sponsor ID: 1199.227