Oral immunotherapy with type V collagen in idiopathic pulmonary fibrosis

Eur Respir J. 2015 May;45(5):1393-402. doi: 10.1183/09031936.00105314. Epub 2015 Jan 22.

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.

Trial registration: ClinicalTrials.gov NCT00873860.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Biomarkers / blood
  • Cohort Studies
  • Collagen Type V / therapeutic use*
  • Complement C1q / metabolism
  • Female
  • Humans
  • Idiopathic Pulmonary Fibrosis / immunology*
  • Idiopathic Pulmonary Fibrosis / therapy*
  • Immunotherapy / methods*
  • Lung / immunology
  • Male
  • Matrix Metalloproteinase 7 / blood
  • Middle Aged
  • Patient Safety
  • Respiratory Function Tests
  • Serum Albumin / metabolism
  • Vital Capacity / drug effects

Substances

  • Biomarkers
  • Collagen Type V
  • Serum Albumin
  • Complement C1q
  • MMP7 protein, human
  • Matrix Metalloproteinase 7

Associated data

  • ClinicalTrials.gov/NCT00873860