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.
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