Ongoing Research and Clinical Trials

ALOFT-IPF: A Study to Evaluate the Efficacy, Safety, and Tolerability of BMS-986278 in Participants With Idiopathic Pulmonary Fibrosis

Summary: The purpose of this study is to evaluate the efficacy, safety, and tolerability of BMS-986278 in participants with Idiopathic Pulmonary Fibrosis.

• Status: Enrolling
• Clinical Trials ID: NCT06003426
• Sponsor: Bristol Myers Squibb

ALOFT-PPF: A Study to Evaluate the Efficacy, Safety, and Tolerability of BMS-986278 in Participants With Progressive Pulmonary Fibrosis

Summary: The purpose of this study is to evaluate the efficacy, safety, and tolerability of BMS-986278 in Participants with Progressive Pulmonary Fibrosis.

• Status: Enrolling
• Clinical Trials ID: NCT06025578
• Sponsor: Bristol Myers Squibb

Study of Oral Epigallocatechin-3-gallate (EGCG) in IPF Patients

Summary: This is a multi-center, double-blind, placebo-controlled, dose-ranging Phase I study of once daily EGCG administered for 12 weeks. The study will assess safety, pharmacokinetics, and biomarker measurements of drug effect in IPF patients already receiving background therapy for IPF with either nintedanib or pirfenidone. Two different doses of EGCG will be studied.

• Status: Enrolling
• Clinical Trials ID: NCT05195918
• Sponsor: Hal Chapman, University of California, San Francisco

FIBRONEER-ILD: A double-blind, randomized, placebo-controlled trial evaluating the efficacy and safety of BI 1015550 over at least 52 weeks in patients with Progressive Fibrosing Interstitial Lung Diseases (PF-ILDs)

Summary: The purpose of this study is to find out whether a medicine called BI 1015550 can help people with Progressive Fibrosing Interstitial Lung Diseases (PF-ILDs). People who have a form of PF-ILD other than Idiopathic Pulmonary Fibrosis (IPF) can join the study. If they already take nintedanib, they can continue treatment throughout the study.

• Status: Active, not enrolling
• Clinical Trials ID: NCT05321082
• Sponsor: Boehringer Ingelheim

PRECISIONS: Prospective tReatment EffiCacy in IPF uSIng genOtype for Nac Selection (PRECISIONS) Trial

Summary: Hypothesis: Patients with idiopathic pulmonary fibrosis (IPF) that have the TOLLIP rs3750920 TT genotype will exhibit improved clinical outcomes when treated with N-acetyl cysteine (NAC) compared to placebo, while receiving standard care.

• Status: Enrolling
• Clinical Trials ID: NCT04300920
• Sponsor: University of Michigan

Imaging Evaluation of PLN-74809 in Participants With IPF (PLN-74809) (PLN-74809)

Summary: This is a Phase 2a, single -center, randomized, double-blind, placebo-controlled study to evaluate type 1 collagen deposition in the lungs following once-daily treatment with PLN-74809 for 12-weeks. This study is occurring at Massachusetts General Hospital.

• Status: Enrolling
  
• Clinical Trials ID: NCT05621252
  
• Sponsor: Pliant Therapeutics, Inc.

Innate Immunity in Idiopathic Pulmonary Fibrosis

• Status: Enrolling
• Sponsor: DARPA

Contrast-enhanced Lung MRI to Assess Disease Activity in Fibrotic Interstitial Lung Disease

• Status: Enrolling
• Sponsor: Chest Research Foundation

Preliminary Evaluation of [68Ga]CBP8 in Healthy Individuals, Lung Cancer, and Idiopathic Pulmonary Fibrosis Patients: Preliminary evaluation of [68Ga]CBP8 (ColliBright) in healthy individuals, in lung cancer patients undergoing radiation therapy prior to the resection of locally advanced tumors, and in idiopathic pulmonary fibrosis patients.

Summary: The goal of this study is to investigate the safety of [68Ga]CBP8 and its efficacy to detect collagen deposition in pulmonary fibrosis.

• Status: Enrolling
• Clinical Trials ID: NCT03535545
• Sponsor: NIH-NHLBI

Exhaled Breath Condensate and Plasma Collection for Interstitial Lung Diseases (ILDs)

• Status: Enrolling
• Sponsor: Merck

Longitudinal assessment of pulmonary fibrosis with OCT

• Status: Enrolling
• Sponsor: Boehringer Ingelheim Pharmaceuticals, Inc.

Evaluating pulmonary fibrosis with optical coherence tomography: Pilot Study

• Status: Not enrolling
• Sponsor: NIH-NHLBI

Biorepository for Interstitial Lung Diseases (ILDs)

• Status: Enrolling
• Sponsor: Scleroderma Foundation

Pulmonary Fibrosis Foundation Patient Registry (Data entry)

• Status: Follow up
• Sponsor: University of Michigan

Pulmonary Fibrosis Foundation Bioregistry (Blood draw)

• Status: Follow up
• Sponsor: University of Michigan

My overarching interest is in fostering translational research, especially basic science using human sample-derived models, with the goal of understanding pathways that could treat, cure, or prevent interstitial lung disease. To this end, I organize an ongoing tissue bank to collect lung and other samples from patients undergoing lung transplant or other lung surgeries, and of collaborating with other investigators working on ILD and other severe lung diseases. In addition, I have worked on improving models of epithelial cell-fibroblast interactions, and have ongoing interest in autoimmune ILD, acute exacerbations and critical illness in ILD, and in and lung transplantation.

My research focuses on the development and application of advanced imaging methods to characterize the pathogenesis of pulmonary fibrosis. We use multi-modal (PET, MRI, HRCT) and multiparametric lung imaging for early detection and quantitative assessment of disease, to better inform prognosis, and to provide an early measure of treatment response. Our lab has developed novel molecular probes for PET imaging of fibrosis, fibrogenesis, and specific markers of fibrosis pathobiology, and translated these probes for use in human research. Our work encompasses both clinical and preclinical research and we have active projects involving different fibrosing lung disease such as idiopathic pulmonary fibrosis, radiation induced lung injury, and systemic sclerosis.

Dr. Chivukula conducts basic scientific research in the Sabatini group at the Whitehead Institute for Biomedical Research. His prior work has elucidated novel in vivo roles for microRNAs in mammals and revealed a previously undescribed form of human lung disease caused by short airway cilia. His current work focuses on the roles of lysosome dysfunction in driving genetic and sporadic forms of interstitial lung disease. Dr. Chivukula’s research has been recognized with the Michael A. Shanoff Award, selection to Forbes Magazine “30 Under 30”, and with selection as a fellow of the Parker B. Francis Foundation.

My research focuses on factors that influence outcomes in patients with various types of interstitial lung disease (ILD), including pulmonary fibrosis. I aim to better characterize the natural history of disease phenotypes in different ILD patient populations through their link to autoantibodies, with the ultimate goal being to optimize treatment algorithms. My work has afforded me the privilege to collaborate with colleagues across multiple disciplines, including but not limited to Radiology, Pathology, and Rheumatology. In parallel, I am an investigator on several clinical trials related to pulmonary fibrosis.

My research program is focused on 1) better understanding the pathogenesis of fibrotic diseases in the lung, including IPF, and 2) using that understanding to develop novel therapies to help patients with pulmonary fibrosis. I began by studying a key cytoskeletal regulation enzyme, Rho kinase (ROCK) and its role in pro-fibrotic signaling in pulmonary epithelial cells, endothelial cells and fibroblasts. Based on a striking phenotype in ROCK haploinsufficient mice who were protected from vascular permeability in addition to fibrosis in the bleomycin model, I have focused my K08 work on the role of vascular permeability in pulmonary fibrosis. I am studying the ROCK signaling pathway in addition to bioactive lipid signaling by fibrotic mediators LPA and S1P. There is also accumulating evidence from human studies that there are abnormalities in the pulmonary endothelium in patients who develop pulmonary fibrosis, such as increased vascular permeability, but also loss of capillaries and expansion of bronchial vessels. The mechanisms behind these observations remain poorly understood and the cause/effect relationship between the endothelium and the subsequent development of fibrosis has yet to be defined. I am currently focused on identifying vascular abnormalities in pulmonary fibrosis that may provide opportunities for early detection of patients likely to experience disease progression and for early therapeutic intervention for this devastating disease.

Despite recent approval of two new therapies, many patients with idiopathic pulmonary fibrosis (IPF) continue to have progressive disease, impaired exercise capacity, and poor quality of life. Clearly more effective and targeted therapy for IPF could have a positive impact on the well-being of the numerous people affected by this disease. Endothelial cell dysfunction and exaggerated vascular permeability are cardinal components of the initial pathways activated in response to repetitive lung injury. We and others have demonstrated that endothelial cell dysfunction and unresolved vascular leak in the lung is not simply a consequence of pulmonary fibrosis, but a central contributor to its progression. Despite these observations, mitigating the vascular responses that lead to hyperpermeability and fibrosis have received relatively little investigative attention. The lab seeks to (1) understand the roles of endothelial ROCK1 and ROCK2 in the vascular response to lung injury and in the development of pulmonary fibrosis; and (2) to investigate whether the endothelial-specific delivery of ROCK inhibitors can halt the progression of lung fibrosis.

My research focuses on using advanced and molecular imaging to assess disease activity in pulmonary fibrosis. Together with collaborators at the MGH Martinos Center for Biomedical Imaging and the laboratory of Dr. Peter Caravan, we have translated the first type I collagen-specific positron emission tomography (PET) probe into humans for non-invasive detection of lung fibrosis. We are currently investigating the ability of this probe to predict disease progression in patients with pulmonary fibrosis. In addition, we are using advanced magnetic resonance imaging (MRI) techniques to detect changes in the microvasculature of fibrotic lungs to better understand the significance of these changes during the course of the disease. The goal of this research is to be able to more accurately assess disease activity and ultimately be able to incorporate these imaging techniques in clinical trials for early assessment of treatment response.

Dr. Shea’s research focus is exploring the mechanisms that lead to lung fibrosis and exploring new treatments for this disease process. His research has included basic science, translational, and clinical investigations, and he has received NIH funding for his work. He is currently exploring the use of a novel molecular imaging technique to assess the extent of ongoing lung injury in pulmonary fibrosis, and he is an investigator for several industry-sponsored clinical trials in idiopathic pulmonary fibrosis (IPF) and other fibrotic lung diseases.