This 76-week, 3-part Phase 1b/2 study is intended to evaluate the pharmacological properties (pharmacokinetics and pharmacodynamics), safety, tolerability and preliminary effectiveness of TOFA administrated to young adults (18-45 years) with moderately to severely active SLE-CL. Subjects will be studied at the Cincinnati Children's Hospital Medical Center (CCHMC) and in Cleveland at MetroHealth Medical Center.
Cohort 1 (n=10, weight \> 40kg and age \> 18 years and ≤ 45 years ) will undergo intense PK-sampling to determine exposures following TOFA dosed at 5 mg BID. TOFA dose escalation will not be considered for inadequate response of SLE-CL. Cohort 2 (n=10, weight \> 40kg and age \> 18 years and ≤ 45 years) will be treated with the same dose as Cohort 1. No PK sampling will occur for Cohort 2. Enrollment of Cohort 2 will only start once Cohort 1 has completed 8 weeks of TOFA and results of PK analyses from Cohort 1 are available. * Part A (up to week 8) requires stable background medications; * Part B (up to week 24) allows for tapering of corticosteroids (CS) in the setting of significant clinical improvement of SLE-CL as defined by a decrease in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity score by \>50% from baseline , and * Part C (until week 76) permits tapering of other background medications in subjects with clinical remission of SLE-CL (CLASI activity score=0). TOFA dosing is kept stable during Part C.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
13
Tofacitinib 5 mg twice daily
Cincinnati Childrens Hospital Medical Center
Cincinnati, Ohio, United States
MetroHealth Medical Center
Cleveland, Ohio, United States
Oral Clearance (CL/F) (Cohort 1 Only)
Apparent total clearance of the drug from plasma after oral administration
Time frame: Day 5
Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity Score
Proportion of subjects who achieve a skin response per the validated CLASI The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity score consists of two scores. The first summarizes the activity of the disease while the second is a measure of the damage done by the disease. The Activity Score range is 0-70 with the maximum score (70) indicating the worst outcome. The Damage Score range is 0-80 with the maximum score (80) indicating the worst outcome.
Time frame: weeks 4, 8 and 24 compared to baseline.
AUCt (Cohort 1 Only)
Area under the plasma concentration-time curve linear scale Median Concentration (ng/mL) per nominal time 0-8 hours.
Time frame: Day 5
Cmax (Cohort 1 Only)
Maximum (or peak) plasma concentration of Tofacitinib
Time frame: Day 5
Tmax (Cohort 1 Only)
Time to reach maximum (peak) plasma concentration following administration of Tofacitinib
Time frame: Day 5
Vz/F (Cohort 1 Only)
Apparent volume of distribution during terminal phase after non-intravenous administration
Time frame: Day 5
Half-life of Tofacitinib (Cohort 1 Only)
half-life of Tofacitinib
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Time frame: Day 5
Safety of Tofacitinib: Total Number of Adverse Events is Reported (Cohorts 1 and 2)
Rate and severity of adverse events and lab abnormalities experienced by participants in both cohorts of the research study.
Time frame: 76 weeks