A Phase 2, Open-Label, Dose-Escalation Study to Evaluate the Safety, Tolerability, and Efficacy of FG-3019 in Subjects with Idiopathic Pulmonary Fibrosis
The overall objective of this study is to evaluate the safety of FG-3019 in subjects with iPF and the efficacy of different doses of FG-3019 for attenuating fibrosis in these subjects in two cohorts. Cohort 1 will receive FG-3019 at a dose of 15 mg/kg every 3 weeks, with approximately 52 subjects enrolledat across all sites. This site has not enrolled nor will enroll in Cohort 1. Cohort 2 will enroll a total of 30 subjects who will receive FG-3019 at a dose of 30 mg/kg every three weeks per amendment 2. a previous amendment, amendment 1 was to increase the dose to 45 mg/kg for this cohort but was withdrawn prior to implementation and no subjects were enrolled under that amendment. Safety laboratory testing and clinical safety assessments (vital signs, electrocardiograms, physical examinations) are performed routinely throughout the study. efficacy will be evaluated by examining FG-3019's effects on pulmonary function tests (PFTs) including FVC, DLCo, TLC, and FRC, extent of pulmonary fibrosis (by high resolution computed tomography [HRCT] scans of the chest), assessments of dyspnea, QoL, and biomarkers including blood levels of CTGF. The total duration of the study for participants at this site (Cohort 2) is up to 58 weeks, divided into Screening Period (up to 6 weeks), Treatment Period (45 weeks), and Follow-up Period (7 weeks).
1. Age 35 to 80 years, inclusive.
2. Clinical diagnosis of IPF along with diagnostic criteria defined by current international guidelines (Raghu, 2011). Each subject must have one of the following: (1) Usual Interstitial Pneumonia (UIP) Pattern on an available HRCT scan prior to Screening Visit 1; or (2) Possible UIP Pattern on an available HRCT scan prior to Screening Visit 1 and surgical lung biopsy within 5 years of Screening Visit 1 showing UIP Pattern.
3. History of IPF of <=5 years[Single Quote] duration with onset defined as the date of the first diagnosis of IPF by HRCT or surgical lung biopsy.
4. Evidence of progression of IPF within 18 months preceding Screening Visit 1, defined as worsening of abnormalities attributed to IPF on HRCT or decline in FVC percent of predicted value by 10% or more.
c. Other evidence of disease progression based on objective measures (e.g., other PFTs, oxyhemoglobin saturation [SaO2], 6-minute walk distance [6-MWD], chest radiograph, new or increased supplemental oxygen requirements) may be acceptable, but approval by the FibroGen medical monitor is required.
5. Interstitial pulmonary fibrosis defined by HRCT scan at Screening Visit 2, with evidence of >=10% to <50% parenchymal fibrosis (reticulation) and <25% honeycombing, within the whole lung.
6. FVC criteria (Cohort 2): FVC percent predicted >=55% at Screening Visit 1.
7. Female subjects of childbearing potential (including those <1 year postmenopausal) must be willing to use a medically acceptable method of contraception, for example, an oral
contraceptive, depot progesterone, or intrauterine device. Male subjects with female partners of childbearing potentialwho are not using birth control as described above must use a barrier method of contraception (e.g., condom) if not surgically sterile (i.e., vasectomy). Contraceptive methods
must be practiced upon entering the trial and through 3 months after the last dose of FG-3019.