Fig 1.
Graphical outline of the design and conduct of the study.
Table 1.
Patient demographics and baseline disease characteristics.
Table 2.
Summary of treatment-emergent adverse events.
Fig 2.
Individual values for total drug exposure based on mean Cmax (A) and AUClast (B) for both the 30mcg/dose group (closed circles) and the 60mcg/dose group (open squares). Individual drug exposure levels correlated with body weight for Cmax (C) and AUClast (D). Individual drug exposure levels from the 60 mcg/dose group separated by those who had an improvement in target lesion response, responders (open square), vs those who did not yet show improvement, nonresponders (hatched square) based on Cmax (E) and AUClast (F).
Table 3.
Summary of pharmacokinetic parameters at Day 1 and Day 29.
Fig 3.
Individual TLIGA scores over time.
Placebo group (A), 30 mcg/dose group (B), and 60 mcg/dose group (C). Dalazatide clinical activity shown as improvement in target lesion for a patient after 4 weeks of treatment from the 60 mcg/dose group (D). Individual TLIGA responses by baseline body weight in the 60 mcg/dose group at Day 32 (E). R = improvement in target lesion; NR = no improvement. Bars indicate mean body weight for each subgroup.
Table 4.
Body weight and percent change in PASI score of TLIGA responders and non-responders.
Fig 4.
Individual PASI scores at baseline and Day 32.
Placebo group (A), 30 mcg/dose group (B), and 60 mcg/dose group (C). *P < 0.01, two-tailed student’s t-test.
Fig 5.
Change in PASI score for 60 mcg/dose group based on body weight above the median or below the median. Bars indicated mean % change in PASI.
Table 5.
Efficacy outcomes.
Fig 6.
Dalazatide inhibits multiple soluble mediators of inflammation associated with psoriasis.
PL = placebo group; R = improvement in target lesion, NR = no improvement in target lesion 60 mcg/dose dalazatide group. Data represent mean ± SEM of the % change from Day 32 relative to baseline (Day 1). **P < 0.01, two-tailed student’s t-test.
Fig 7.
Dalazatide treatment reduces the expression of activation markers HLA-DR, Ki67 and CD40L by memory T cells from psoriasis patients.
(A, B) The proportion of CD2+ memory T cells from the peripheral blood from placebo (PAL) and dalazatide (DAL, 60 μχγ/dose) treated patient samples were analyzed for the proportion of the indicated subpopulation and the % change from Day 29 relative to Day 1 calculated. A) HLA-DR expression, B) Ki67 expression, C) CD40L expression after PMA/ionomycin treatment. Samples were collected on Day 1 pre-dose and Day 29 post-dose. The CD40L+ populations as a percentage of CD4+ or CD8+ memory T cells were measured following an ex vivo culture of PBMC with 0.2 nM PMA and ionomycin (250 ng/mL) or media alone for 6 hours. The percentage of cells expressing CD40L in response to PMA/ionomycin was calculated as: %CD40L+(stimulated) = %CD40L+(PMA+Ionomycin)-%CD40L+(Media alone). Data represent the mean ± SEM of the % change from Day 29 relative to Day 1. Statistical analysis between placebo and dalazatide groups was performed using one-tailed Student’s t-test. *P < 0.05. **P<0.01