The European Respiratory Journal ( ERJ ) published a manuscript entitled, FG-3019 anti-connective tissue growth factor monoclonal antibody: results of an open-label clinical trial in IPF, from a phase 2 clinical study in subjects with idiopathic pulmonary fibrosis ( IPF ) treated for 48 weeks with the investigational drug FG-3019, a monoclonal antibody that inhibits the activity of connective tissue growth factor ( CTGF ), a central mediator of fibrotic disease.
In the study, lung fibrosis, as measured by quantitative high resolution computed tomography ( HRCT ), was shown to be reduced in a portion of subjects who received FG-3019.
Subjects with reduced or stable fibrosis showed lung function results that were better overall than those for whom fibrosis continued to increase.
The exploratory study enrolled patients with a wide range of idiopathic pulmonary fibrosis severity to assess safety and efficacy of FG-3019.
While other recent clinical trials in idiopathic pulmonary fibrosis have assessed efficacy in terms of changes in pulmonary function, this phase 2 open-label study measured efficacy by changes in both pulmonary function, measured by forced vital capacity ( FVC ), and pulmonary fibrosis, assessed using quantitative high resolution computed tomography ( HRCT ), the tool employed to confirm diagnosis of idiopathic pulmonary fibrosis.
Subjects in two cohorts received intravenous doses of FG-3019 of either 15 mg/kg or 30 mg/kg every three weeks for 45 weeks.
The publication provides an analysis of safety and efficacy data from all subjects treated in the study.
Of the 89 subjects who received one or more doses, 75 subjects completed 24 weeks and 66 of these subjects completed 48 weeks of treatment and assessment of changes in pulmonary structure and function.
Based on results obtained in pre-clinical studies in radiation-induced pulmonary fibrosis, hypothesis was that FG-3019 treatment could reverse lung fibrosis.
Extent of and changes in lung fibrosis were assessed using quantitative time series of HRCT imaging at baseline, week 24, and week 48.
Quantitative HRCT is a computer-based imaging method to measure fibrotic profile and changes in fibrosis affecting lung tissue over time.
Other peer-reviewed publications based on similar quantitative HRCT methods have identified an association between fibrosis worsening and mortality in idiopathic pulmonary fibrosis.
While the majority of subjects in the study ( 65% ) exhibited an increase in fibrosis, 35% exhibited stable or improved fibrosis at week 48 as measured by HRCT.
Furthermore, at both 24 and 48 week time points, improvements in lung fibrosis correlated with improvements in lung function.
This is the first clinical trial to indicate improvement in fibrosis in patients with idiopathic pulmonary fibrosis.
The two doses of FG-3019 administered to patients with idiopathic pulmonary fibrosis by intravenous infusion every 3 weeks for 45 weeks were well tolerated in the patients enrolled in this study.
Adverse events were generally mild. Twenty-four of 89 treated subjects ( 27.0% ) experienced a total of 38 treatment-emergent serious adverse events during the trial. The type and frequency of serious adverse events were consistent with those expected in the study population.
Subjects with a wide range of disease severity were enrolled in the trial.
In the initial cohort, inclusion criteria were FVC values from 45% to 90% predicted.
After the results across that population were studied, the FVC inclusion range was shifted to FVC values of 55% predicted or greater in the second cohort.
The study was designed to be open-label and thus did not include a placebo control group.
FG-3019-treated subjects in this study showed an average FVC decline from baseline of 140 mL over the treatment period of 48 weeks.
Of the subjects who completed a 48-week course of treatment, 13.6% experienced FVC% predicted decline from baseline of greater than or equal to10%, while 30% of treated subjects showed an increase from baseline of FVC% predicted ( range 0.2–14.1% ). ( Xagena )
Source: FibroGen, 2016