National Jewish Health

About: National Jewish Health is a healthcare organization based out in Denver, Colorado, United States. It is known for research contribution in the topics: T cell & Asthma. The organization has 883 authors who have published 833 publications receiving 79201 citations. The organization is also known as: National Jewish Medical and Research Center.

Pamrevlumab (FG-3019), an Anti-Connective Tissue Growth Factor Therapy for Idiopathic Pulmonary Fibrosis: A Randomized, Double-Blind, Placebo-Controlled Trial

Abstract: Background: This Phase 2 study evaluated the safety, tolerability, and efficacy of pamrevlumab (FG-3019), a human monoclonal antibody against connective tissue growth factor, in idiopathic pulmonary fibrosis (IPF). The study was designed to evaluate if pamrevlumab could slow, stop, or reverse IPF progression and to measure average magnitude of effect. Methods: In this double-blind, placebo-controlled study (NCT01890265), patients at 39 sites (7 countries) were randomized 1:1 using interactive responsive technology to pamrevlumab 30mg/kg or placebo IV infusion, every 3 weeks over 48 weeks (total of 16 infusions). Primary efficacy endpoint was change from baseline in forced vital capacity (FVC) %-predicted at Week 48. Findings: Between August 2013 and July 2017, 103 patients were randomized to pamrevlumab 30mg/kg (n=50) or placebo (n=53). All patients received at least one dose and were analyzed for safety. For the efficacy analyses, two placebo patients in the intention-to-treat population were excluded due to enrollment error. Pamrevlumab reduced FVC %-predicted decline by 60.3% at Week 48 (-2.9% pamrevlumab vs. 7.2% placebo; a difference of 4.3%; 95% CI 0.35-8.30; P=0.033). The proportion of pamrevlumab patients with FVC %-predicted decline ≥10% or death was lower at all visits (10.0% vs. 31.4% at Week 48; P=0.010). Quantitative Lung Fibrosis/High Resolution Computer Tomography score was significantly lower in pamrevlumab group vs. placebo at Weeks 24 (24.8 vs. 86.4mL; P=0.009) and 48 (75.4 vs. 151.5mL; P=0.038). Pamrevlumab was well tolerated with a safety profile comparable to placebo. Treatment-emergent SAEs were observed in 12 (24.0%) and 8 (15.1%) patients in pamrevlumab and placebo arms with 3 and 7 patients discontinuing, respectively. Of three (6.0%) deaths in the pamrevlumab arm and six (11.3%) on placebo, none were considered treatment-related. Interpretation: In this Phase 2 trial, pamrevlumab attenuated IPF progression and was well tolerated. Trial Registration Number: NCT01890265. Funding: Sponsored and funded by FibroGen, Inc., San Francisco, CA, USA. Declaration of Interest: LR reports grants from Boehringer Ingelheim and Roche outside of the submitted, personal fees from FibroGen during the conduct of the study, personal fees from Biogen, personal fees from Sanofi-Aventis, personal fees from Roche, personal fees from Boehringer Ingelheim, personal fees from Pliant Therapeutics, personal fees from Promedior, personal fees from Asahi Kasei, personal fees from RespiVant, personal fees from Nitto, personal fees from Celgene, personal fees from Prometic, personal fees from Zambon, personal fees from Veracyte, personal fees from Toray, outside the submitted work; EFP reports grants from Genentech, grants from Boehringer Ingelheim, outside the submitted work; UC reports personal fees and non-financial support from Boehringer, personal fees and non-financial support from Roche, personal fees and non-financial support from Bayer, personal fees from GSK, personal fees from UCB Celltech, personal fees from Biogen, personal fees from FibroGen, personal fees from Global Blood Therapeutics, personal fees from Astra Zeneca, outside the submitted work; CA reports personal fees from ROCHE , personal fees from Boehringer Ingelheim, personal fees from FibroGen, personal fees from GSK, personal fees from Bayer, grants from Boehringer Ingelheim, grants from Roche, personal fees from MSD, outside the submitted work; DJL reports grants and personal fees from FibroGen, during the conduct of the study; personal fees from Galapagos, personal fees from Roche, personal fees from Sanofi Genzyme, personal fees from Philips Respironics, grants and personal fees from Global Blood Therapeutics, other from Galecto, personal fees from Veracyte, other from Pulmonary Fibrosis Foundation, from Boehringer-Ingelheim, outside the submitted work; DJL no longer accepts fees for industry consulting work as of May 2018; KRF reports personal fees from Veracyte, grants and personal fees from Roche/Genentech, grants and personal fees from Boehringer Ingelheim, personal fees from Sanofi Genzyme, outside the submitted work; NE has nothing to disclose; RP has nothing to disclose; MBS reports other from Boehringer Ingelheim, other from Genentech, has a patent Apparatus, Compositions and Methods for Assessment of Chronic Obstructive Pulmonary Disease Progression among Rapid and Slow Decline Conditions issued; JG has nothing to disclose; KPY is employed by FibroGen; TN is employed by FibroGen; SP has two patents US9,480,449 and EP 2844291 issued, and was an employee of FibroGen at the time of the study; MZ is employed by FibroGen; EG reports personal fees from FibroGen during the conduct of the study, and was an employee of FibroGen at the time of the study; EK is employed by FibroGen; GR reports other from FibroGen, during the conduct of the study; other from Avalyn, personal fees and other from Boehringer Ingelheim, other from BMS, other from Bellerophan, other from Gilead, other from Promedior, other from RocheGenentech, other from Respivant, and other from Sanofi, personal fees and other from Veracyte, grants from NIH, outside the submitted work. Ethical Approval: The clinical study protocol, its amendments, and the informed consent form were approved by Independent Ethics Committees, Institutional Review Boards, and/or Research Ethics Boards, and the study was conducted in accordance with the ethical principles of Good Clinical Practice and the Declaration of Helsinki.