This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.OBJECTIVES: ' The purpose of this research study is to assess the safety, tolerability, and effectiveness of a single dose of this investigational agent which is being studied for the treatment of systemic lupus erythematosus (SLE). ' To characterise the pharmacokinetics (PK) and pharmacodynamics (PD) of TACI-Fc5 in SLE patients following a single subcutaneous dose, and to monitor its effects on selected biological markers of disease activity.STUDY DESIGN: Thirty-two male and female patients will be included (as 4 cohorts of 8). Each will undergo assessment at a pre-study visit within 14 days before administration of the investigational product, and will receive a single subcutaneous dose of TACI-Fc5 or corresponding placebo. Up to four doses of TACI-Fc5 will be assessed. The first cohort will be administered a single subcutaneous dose of TACI-Fc5 at a dose of 0.3 mg/kg. Subsequent cohorts will receive doses based upon the dose-escalation decision algorithm, up to a maximal dose of 9 mg/kg. Patients will attend the clinic on the day of investigational medicinal product administration (Study Day 1) and remain resident until after the 12 hour Pharmacokinetic/Pharmacodynamic blood samples have been collected. They will return to the clinic on an outpatient basis for post-dose procedures that include collection of pharmacokinetic and pharmacodynamic samples and safety assessments conducted at pre-defined intervals up to 6 weeks following dosing. A post-study visit is scheduled to take place 6 wks ( 2 days) following dosing. STUDY POPULATION AND MAIN ELIGIBILITY CRITERIA: Male and female patients aged 18 to 70 years with proven diagnosis of SLE with at least 4 of the ACR criteria at the time of screening and SLE disease activity index (SELENA SLEDAI) score 0 - 8. Thirty-two patients were distributed between 3 US study sites. INVESTIGATIONAL PRODUCT: The liquid formulation of TACI-Fc5 will be provided in vials filled to deliver 0.5 mL and containing 70 mg of TACI-Fc5. The placebo will be provided in vials filled to deliver 0.5 mL SQ. DATA ANALYSIS AND STATISTICS: The primary objective of the study is to perform an assessment of the systemic and local tolerability of TACI-Fc5 in patients with SLE. This will be achieved through monitoring of: vital signs, ECGs and laboratory parameters (including hematology, coagulation, clinical chemistry and urinalysis). Close monitoring of adverse events will be conducted throughout the study in addition to regular assessments of the injection site for evidence of localized reactions. The secondary objective of the study is to characterize the pharmacokinetics and pharmacodynamics of TACI-Fc5 in SLE patients and to monitor the effects on the biological marker of disease activity. Additional biological markers endpoints of the study will be the assessment of lymphocyte subsets, serum concentrations of free BLyS, BLyS/TACI-Fc5 complex, IgG and IgM and anti-dsDNA antibodies up to 6 weeks post-dose. Serum levels of anti-TACI-Fc5 antibodies will be measured at pre-dose on day 1 and at the post-study visit. The assessment will include the evaluation over time and change from baseline for all the markers above.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
General Clinical Research Centers Program (M01)
Project #
Application #
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Stanford University
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Evangelou, Evangelos (see original citation for additional authors) (2018) Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits. Nat Genet 50:1412-1425
Doherty, Aiden; Smith-Byrne, Karl; Ferreira, Teresa et al. (2018) GWAS identifies 14 loci for device-measured physical activity and sleep duration. Nat Commun 9:5257
Askie, Lisa M; Darlow, Brian A; Finer, Neil et al. (2018) Association Between Oxygen Saturation Targeting and Death or Disability in Extremely Preterm Infants in the Neonatal Oxygenation Prospective Meta-analysis Collaboration. JAMA 319:2190-2201
Frayling, Timothy M; Beaumont, Robin N; Jones, Samuel E et al. (2018) A Common Allele in FGF21 Associated with Sugar Intake Is Associated with Body Shape, Lower Total Body-Fat Percentage, and Higher Blood Pressure. Cell Rep 23:327-336
Latva-Rasku, Aino; Honka, Miikka-Juhani; Stan?áková, Alena et al. (2018) A Partial Loss-of-Function Variant in AKT2 Is Associated With Reduced Insulin-Mediated Glucose Uptake in Multiple Insulin-Sensitive Tissues: A Genotype-Based Callback Positron Emission Tomography Study. Diabetes 67:334-342
Srinivasan, Lakshmi; Page, Grier; Kirpalani, Haresh et al. (2017) Genome-wide association study of sepsis in extremely premature infants. Arch Dis Child Fetal Neonatal Ed 102:F439-F445
Di Fiore, Juliann M; Martin, Richard J; Li, Hong et al. (2017) Patterns of Oxygenation, Mortality, and Growth Status in the Surfactant Positive Pressure and Oxygen Trial Cohort. J Pediatr 186:49-56.e1
Denson, Lee A; McDonald, Scott A; Das, Abhik et al. (2017) Early Elevation in Interleukin-6 is Associated with Reduced Growth in Extremely Low Birth Weight Infants. Am J Perinatol 34:240-247
Holmes, Michael V; Pulit, Sara L; Lindgren, Cecilia M (2017) Genetic and epigenetic studies of adiposity and cardiometabolic disease. Genome Med 9:82
Younge, Noelle; Goldstein, Ricki F; Bann, Carla M et al. (2017) Survival and Neurodevelopmental Outcomes among Periviable Infants. N Engl J Med 376:617-628

Showing the most recent 10 out of 589 publications