title: Oral immunotherapy with type V collagen in idiopathic pulmonary fibrosis.
abstract: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with poor prognosis. IPF appears to be heterogeneous in pathobiology with ∼40% of IPF patients found to have elevated levels of circulating antibodies to the autoantigen type V collagen (col(V)). Following a targeted, precision medicine approach, we conducted a phase 1 study to test the safety and explore potential efficacy of IW001, a col(V) oral immunotherapeutic developed to treat antibody-positive IPF patients. We divided 30 antibody-positive IPF patients into three cohorts for daily dosing over a 24-week period. All patients completed treatment without serious adverse events, acute exacerbations or IPF-related hospitalisations. A decline in lung function occurred in the lowest-dose cohort that was comparable to that reported in placebo arms of published IPF trials. In contrast, the highest-dose cohort showed a trend toward stabilisation of forced vital capacity and matrix metalloproteinase 7, and a reduction in binding of C1q to anti-col(V) antibodies. IW001 may modulate the immune response to col(V) and may represent a new therapeutic for col(V)- reactive IPF patients.
authors.affiliation: ImmuneWorks, Inc., Indianapolis, IN, USA Dept of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA Dept of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA dwilkes@iu.edu.
authors.forename: David S
authors.initials: DS
authors.lastname: Wilkes
authors.affiliation: ImmuneWorks, Inc., Indianapolis, IN, USA.
authors.forename: Terrence
authors.initials: T
authors.lastname: Chew
authors.affiliation: Dept of Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Flaherty
authors.affiliation: ImmuneWorks, Inc., Indianapolis, IN, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Frye
authors.affiliation: Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Kevin F
authors.initials: KF
authors.lastname: Gibson
authors.affiliation: Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA.
authors.forename: Naftali
authors.initials: N
authors.lastname: Kaminski
authors.affiliation: ImmuneWorks, Inc., Indianapolis, IN, USA Dept of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Klemsz
authors.affiliation: ImmuneWorks, Inc., Indianapolis, IN, USA.
authors.forename: Wade
authors.initials: W
authors.lastname: Lange
authors.affiliation: Dept of Medicine, University of Chicago Pritzker School of Medicine, Chicago, IL, USA.
authors.forename: Imre
authors.initials: I
authors.lastname: Noth
authors.affiliation: ImmuneWorks, Inc., Indianapolis, IN, USA.
authors.forename: Katia
authors.initials: K
authors.lastname: Rothhaar
mesh_terms: D000284:Administration, Oral; D000368:Aged; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D024062:Collagen Type V / Q000627:therapeutic use*; D015922:Complement C1q / Q000378:metabolism; D005260:Female; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000276:immunology* / Q000628:therapy*; D007167:Immunotherapy / Q000379:methods*; D008168:Lung / Q000276:immunology; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000097:blood; D008875:Middle Aged; D061214:Patient Safety; D012129:Respiratory Function Tests; D012709:Serum Albumin / Q000378:metabolism; D014797:Vital Capacity / Q000187:drug effects
chemical_list: D015415:Biomarkers; D024062:Collagen Type V; D012709:Serum Albumin; D015922:Complement C1q; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7