Download Safety and Efficacy of PRTX-100, a Highly Purified Form of

SafetyandEfficacyofPRTX-100,aHighlyPurifiedFormofStaphylococcalProteinA,inPatientswith
ImmuneThrombocytopenia(ITP)
JamesB.Bussel,DavidJ.Kuter,SylvainAudia,RichardJ.Francovitch,andMarcMichel
Background: ITP is a rare autoimmune hematologic disorder characterized by isolated
thrombocytopenia caused by antibody-dependent platelet destruction and impaired platelet
production. Several therapeutic options (eg glucocorticoids, intravenous immunoglobulin and
thrombopoietin receptor agonists) are available to treat patients with ITP, although inadequate
efficacy,sideeffectsand/orcostcanmakethemundesirable.PRTX-100isahighlypurifiedformof
StaphylococcalproteinA(SpA),whichbindstohumanB-lymphocytesandmonocytes,andmodulates
immune processes. Preclinical data indicate that PRTX-100 may have the potential to treat ITP by
reducingimmune-mediateddestructionofplatelets.Herewepresentsafety/efficacydatafromthe
scheduledanalysisfordoseescalationfromtheinitialdosecohortsofpatientswithITPenrolledin
twoPhase1/2open-labelstudies,PRTX-100-202andPRTX-100-203.
Methods: Adult patients with persistent/chronic ITP and either a platelet count <30,000/µL (if not
receivinganyITPtherapy)oraplateletcountof<50,000/µL(ifreceivingaconstantdoseofpermitted
ITPtreatment)wereeligibleforinclusion.Study202requirespriortreatmentwithathrombopoietin
receptoragonist(TPO-RA)plusoneadditionalstandardITPtreatment,whileStudy203onlyrequires
priortreatmentwithonestandardITPtreatment.Inbothstudies,PRTX-100wasadministeredviaa
30-min infusion (60 min if total dose >500 µg) on Days 1, 8, 15 and 22 in a standard 3 + 3 doseescalationdesign.Startingdosewas1µg/kg(Study202)or3µg/kg(Study203)withsubsequentdose
increasesplanneduptoamaximumof24µg/kg.PlateletcountsweremonitoredonDays1,3,8,15,
22,29,36,43,50,78and106.Safetyanalysesincludedconsiderationofadverseevents(AEs),serious
AEs,infusionreactions,clinicallaboratorytests,vitalsigns,physicalfindingsandelectrocardiograms.
Thekeyefficacyendpointwasplateletresponsedefinedas:aplateletcount≥30,000/µLandatleast
a doubling of baseline platelet count in patients with a baseline platelet count <30,000/µL; or, in
patients receiving permitted treatments for ITP with a baseline platelet count ≥30,000/µL and
<50,000/µL,anincreaseinplateletcountto≥50,000/µLandatleastadoublingofbaselineplatelet
countoranincreaseto>100,000/µL.
Results:Dataareavailablefrom6patients(Study202n=3;Study203n=3)enrolledinthelowest-dose
cohortsofthePRTX-100ITPstudies.Therewere3womenand3menwhowereallCaucasianand
rangedinagefrom49to78years;fourpatientshadasplenectomy.ConcomitantITPmedications
wereprednisone(n=4),dapsone(n=1),andTPO-RAs(n=2).TwopatientsinStudy202receivedfour
dosesofPRTX-100(1µg/kg);threepatientsinStudy203receivedfourdosesofPRTX-100(3µg/kg).
Onepatientreceivingadoseof1µg/kg(Study202)experiencedagrade3vasculitisallergicreaction
anddiscontinuedfromthestudyafter2doses.Thispatienthadahistoryofmilderallergicreactions
toothertherapies.Noadditionalseriousorgrade>3AEsorimmediatelyreportableeventshavebeen
reported for any patient. Three grade 3 laboratory abnormalities have been reported: one patient
(1µg/kg;Study202)experienceddecreasedhemoglobinandhyperkalemia,andonepatient(1µg/kg;
Study202)experiencedhighwhitebloodcellcount.Onegrade1infusionreactionoccurred(itching
rashattheinfusionsiteinonepatientreceiving3µg/kg[Study203]).Nootherinfusionreactionswere
reported.Baselineplateletcountsrangedfrom6,000–30,000/µL.OnepatientinStudy203(3µg/kg)
hadaplateletresponsewithapeakplateletcountof105,000/µLfollowingtheinitiationoftreatment.
Platelet count elevation was observed as early as Day 3 and remained elevated for 2–3 weeks
followingtheinitiationoftreatment(Figure1).
Conclusions:DatafrominitialcohortsintwodoseescalationtrialsofpatientstreatedwithPRTX-100
atadoseof1µg/kgor3µg/kghavedemonstratedanacceptablesafetyprofiletosupportcontinued
enrollmentintohigher-dosecohortsinbothtrials.Aplateletresponsewasobservedinonepatient
treatedatthelowestdoseinoneofthetrials.Enrollmentintohigher-dosecohortsisongoingand
updateddatafrompatientstreatedinthosecohortswillbeincludedinanypresentation.
Figure1