PRM-151, recombinant
human Pentraxin-2 (PTX-2) also referred to as serum amyloid P (SAP), is under development for treatment of fibrosis. A First-in-Human (FIH) trial was performed to assess t
he safety, tolerability, and p
harmacokinetics of sin
gle ascendin
g intravenous doses of PRM-151 administered to
healt
hy subjects, usin
g a randomized, blinded, placebo controlled study desi
gn. Eac
h co
hort included t
hree
healt
hy subjects (PRM-151:placebo; 2:1). SAP levels were assessed usin
g a validated ELISA met
hod, non-discriminatin
g between endo
genous and exo
genous SAP. At a dose level of 10聽m
g/k
g, at w
hic
h a p
hysiolo
gic plasma level of SAP was reac
hed, two additional
healt
hy volunteers and t
hree pulmonary fibrosis (PF) patients were enrolled enablin
g comparison of t
he p
harmacokinetic SAP profile between
healt
hy volunteers and PF patients. In addition, t
he percenta
ge of fibrocytes (CD45+/Procolla
gen-1+ cells) in w
hole blood samples was assessed to demonstrate biolo
gical activity of PRM-151 in t
he tar
get population.
PRM-151 administration was generally well tolerated. In two pulmonary fibrosis patients non-specific, transient skin reactions (urticaria and erythema) were observed. PRM-151 administration resulted in a 6-to 13-fold increase in mean baseline plasma SAP levels at dose levels of 5, 10, and 20聽mg/kg. The estimated t1/2 of PRM-151 in healthy volunteers was 30聽h. Pharmacokinetic profiles were comparable between healthy volunteers and PF patients. PRM-151 administration resulted in a 30-50% decrease in fibrocyte numbers 24聽h post-dose. This suggests that administration of PRM-151 may be associated with a reduction of fibrocytes in PF patients, a population for which current pharmacotherapeutic options are limited. The pharmacological action of PRM-151 should be confirmed in future research.