A randomized, double-blind, placebo-controlled, 52-week study (NCT03068468) evaluated gosuranemab, an anti-tau monoclonal antibody, for progressive supranuclear palsy (PSP). In total, 486 participants dosed were assigned to gosuranemab (n=321) or placebo (n=165).Efficacy was not demonstrated on adjusted mean change of PSP Rating Scale score at week 52 between gosuranemab and placebo (10.4 versus 10.6; P=0.85; primary endpoint) or secondary endpoints, resulting in discontinuation of the open-label long-term extension.Unbound N-terminal tau in cerebrospinal fluid decreased by 98% with gosuranemab and increased by 11% with placebo (P<0.0001). Incidences of AEs and deaths were similar between groups. This well-powered study suggests N-terminal tau neutralization does not translate to clinical efficacy.

Background Tremendous advances have occurred in therapies for peripheral vascular disease (PVD); however, until recently it has not been possible to examine the entire clinical trial portfolio of studies for treatment of PVD (both arterial and venous disease). Methods and Results We examined interventional trials registered in ClinicalTrials.gov from October 2007 through September 2010 (n=40,970) and identified 676 (1.7%) PVD trials (n=493 arterial only, n=170 venous only, n=13 both arterial and venous). Most arterial studies investigated lower extremity peripheral artery disease and acute stroke (35% and 24%, respectively), while most venous studies examined deep vein thrombosis/pulmonary embolus prevention (42%) or venous ulceration (25%). A placebo-controlled trial design was used in 27% of the PVD trials, and 4% of the PVD trials excluded patients aged >65 years. Enrollment in at least 1 US site decreased from 51% in 2007 to 41% of trials in 2010. Compared with non-cardiology disciplines, PVD trials were more likely to be double-blinded, investigate use of devices and procedures, and have industry sponsorship and assumed funding source, and less likely to investigate drug and behavioral therapies. Geographic access to PVD clinical trials within the United States is limited to primarily large metropolitan areas. Conclusions PVD studies represent a small group of trials registered in ClinicalTrials.gov, despite the high prevalence of vascular disease in the general population. This low number, compounded by the decreasing number of PVD trials in the United States, is concerning and may limit the ability to inform current clinical practice of patients with PVD.