Status:Active, not recruiting
Keywords:FibroGen , FG-3019 , Idiopathic Pulmonary Fibrosis , IPF , PF
Sub Specialty: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.
To determine the safety and tolerability of FG-3019 administered at doses of 15 mg/kg (Cohort 1 and Cohort 1-EX) and 30 mg/kg (Cohort 2) by intravenous (IV) infusion every 3 weeks for 45 weeks in the target population (total of 90 weeks of treatment for subjects in Cohort 1-EX)
• To evaluate the effect of FG-3019 on the extent of pulmonary fibrosis in the target population
• To evaluate the effect of FG-3019 on pulmonary function (forced vital capacity [FVC] and diffusing capacity of the lung for carbon monoxide [DLCO]) in the target population
• To evaluate the effect of FG-3019 on dyspnea in the target population
• To evaluate the effect of FG-3019 on health-related quality of life (QoL) in the target population
• To evaluate pharmacokinetic (PK) concentrations, including maximal concentration(Cmax) and minimal concentration (Cmin) in the target population
• To evaluate the effect of FG-3019 on plasma connective tissue growth factor (CTGF) and a panel of serum and plasma biomarkers in the target population
• To evaluate the effect of FG-3019 on lung volumes (total lung capacity [TLC] and functional residual capacity [FRC]) in the target population
• To evaluate the effect of FG-3019 on progression-free survival in the target population
Principle Investigator: Mary Scholand
Principle Department: Pulmonary
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’ 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 a. Cohort 1: Evidence of IPF disease progression within 3-
12 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. Only subjects from Cohort 1 are eligible for treatment in Cohort 1-EX.
b. Cohort 2: Evidence of IPF disease progression 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. Both Cohort 1 and Cohort 2: 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 a. Cohort 1: FVC ≥45% to ≤85% of predicted value at
Screening Visit 1
b. Cohort 1-EX: Less than 3% absolute decrease in FVC percent predicted value from baseline (mean of Screening Visit 1 and Day 1 values from Cohort 1) to the mean of Week 36 and 48 values in the original protocol.
c. 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 potential who 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.
Exclusion Criteria: 1. Female subjects who are pregnant or nursing.
2. Infiltrative lung disease other than IPF, including any of the other types of idiopathic interstitial pneumonias (American Thoracic Society, 2002); lung diseases related to exposure to fibrogenic agents or other environmental toxins or drugs; other types of occupational lung diseases; granulomatous lung diseases; pulmonary vascular diseases; systemic diseases, including vasculitis and connective tissue diseases.
3. HRCT scan findings at Screening Visit 2 Inconsistent with UIP Pattern.
4. Pathology diagnosis on surgical lung biopsy is anything other than UIP Pattern.
5. History of other types of respiratory diseases including diseases or disorders of the airways, lung parenchyma, pleural space, mediastinum, diaphragm, or chest wall that, in the opinion of the investigator, would impact the endpoints in the protocol or otherwise preclude the subject’s participation in the study.
6. History of any other respiratory, cardiovascular, renal, hepatic, metabolic, neurologic, hematologic, or other medical conditions that, in the opinion of the investigator, would preclude the subject’s participation in the study.
7. Clinically important abnormal laboratory tests (including serum creatinine ≥1.5 x upper limit of normal [ULN], hemoglobin <8 g/dL, white blood cells <3,000/mm3, platelets less than 100,000/mm3, international normalized ratio (INR) >1.5, serum albumin <3.0 g/dL, serum total bilirubin >ULN, serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥2 x ULN, or serum alkaline phosphatase ≥2 x ULN.
8. Upper or lower respiratory tract infection of any type within 4 weeks of Screening Visit 1.
9. Acute exacerbation of IPF within 3 months of Screening Visit 1.
10. Evidence of obstructive lung disease by any of the following criteria: Forced Expiratory Volume in One Second/Forced Vital Capacity (FEV1/FVC) ratio <0.65, or residual volume >120 percent of predicted value, or extent of emphysema on HRCT greater than the extent of fibrosis on HRCT.
11. DLCO <30% of the predicted value, corrected for hemoglobin but not for alveolar volume.
12. High likelihood of lung transplantation (in the opinion of the investigator) within 6 months after Day 1.
13. Chronic heart failure categorized as New York Heart Association Class III or IV (this applies to symptoms of chronic heart failure, not IPF); clinical diagnosis of cor pulmonale requiring specific treatment; or severe pulmonary hypertension requiring specific treatment that, in the opinion of the investigator, would preclude the subject’s participation in the study.
14. Use of any of the following medications within 4 weeks preceding Screening Visit 1: warfarin, sildenafil, pirfenidone, azathioprine, cyclophosphamide, interferon gamma-1b, D-penicillamine, methotrexate, cyclosporine, leflunomide, colchicine, bosentan, ambrisentan, aminobenzoate, mycophenolate mofetil, imatinib, relaxin, etanercept, adalimumab, infliximab, anakinra, abatacept, and rituximab.
Note: Treatment of IPF with oral prednisone (or equivalent oral corticosteroid) or N-acetylcysteine (NAC) or both during the Treatment Period is acceptable provided that (1) daily treatment with either or both of these medications has been continuous for at least 4 weeks prior to Screening Visit 1, and (2) daily treatment with either or both of these medications will be continued throughout the Treatment Period at stable doses not to exceed the following: prednisone (or equivalent oral corticosteroid) 10 mg daily, NAC 1800 mg daily.
15. Receipt of any investigational drug within 6 weeks prior to Screening Visit 1.
16. History of cancer of any type in the 5 years preceding Screening Visit 1, excluding non-melanomatous skin cancer, localized bladder cancer, or in situ cervical cancer. Enrollment of subjects with any history of cancer must be pre-approved by the FibroGen medical monitor.
17. Trauma or surgical procedures requiring hospitalization within 4 weeks prior to Screening Visit 1.
18. Planned elective surgery during the study including 4 weeks following the final dose of study drug.
19. History of allergic or anaphylactic reaction to human, humanized, chimeric or murine monoclonal antibodies.
20. The principal investigator judges that the subject will be unable to fully participate in the study and complete it for any reason, including inability to cooperate with study personnel or a history of noncompliance to the medical regimen (i.e., subjects who would be expected to comply poorly with study procedures and treatment), addiction, or any clinically significant medical or psychiatric condition considered a high risk for not successfully completing participation in an investigational study.
21. Body Mass Index (BMI) >35 (Cohort 1); weight >130 kg (Cohort 2).
22. Previous treatment with FG-3019. 23. History of inadequate IV access.