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Contact Pathway Inhibitor to Prevent Vascular Access Failure

Contact Pathway Inhibitor to Prevent Vascular Access Failure
接触途径抑制剂以防止血管通路失败
批准号:
10604057
负责人:
Christina U Lorentz
金额:
$99.85万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2023
资助国家:
美国
项目状态:
已结题
起止时间:
2023-06-01 至 2024-05-31
关键词:
AchievementAcuteAddendumAddressAdverse eventAfrican AmericanAgreementAmerican Society of HematologyAnticoagulantsAnticoagulationArteriovenous fistulaAuthorization documentationAwardBindingBiotechnologyBlack raceBloodBlood VesselsBlood coagulationC-reactive proteinCardiovascular systemCathetersChemistryChronicClinicalClinical DataClinical TrialsCoagulation ProcessComplexComplicationContact InhibitionDataDevelopmentDialysis procedureDoseDouble-Blind MethodDrug KineticsDrug toxicityEnd stage renal failureEvaluationEventExposure toFactor XIFactor XIIFactor XII DeficiencyFailureFeedbackFemaleFibrinolytic AgentsFreeze DryingGoalsGuidelinesHemodialysisHemorrhageHemostatic AgentsHumanHyperplasiaImplantIncidenceIndustryInfectionInflammationInflammatoryInterruptionInterventionKidney FailureLeadLegal patentLifeLongevityMarketingMeasuresMedicalMorbidity - disease rateNo-Observed-Adverse-Effect LevelOutcomeOutcome MeasurePathway interactionsPatientsPharmaceutical PreparationsPharmacodynamicsPharmacologic SubstancePharmacologyPhasePhase II Clinical TrialsPlacebosPlasmaPopulationPrimatesProceduresProsthesisRandomizedRattusRecommendationRecoveryRegimenRenal Replacement TherapyResearchRiskSafetySecureSerumSiteSmall Business Innovation Research GrantSprague-Dawley RatsStenosisSystemTherapeuticTherapeutic antibodiesThrombinThrombosisThrombusToxic effectVenousarteriovenous graftauthorityclinical developmentdrug candidateefficacy outcomesefficacy studyefficacy trialhealth care disparityinhibitorinnovationmalemeetingsmortalityneutralizing antibodynovel strategiespatient populationplacebo controlled studypreclinical safetypreventproduct developmentsafety studyside effectsuccesstargeted treatmentthrombotictreatment duration

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中文摘要
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英文摘要
Project Summary End-stage renal disease (ESRD) patients must maintain chronic vascular access to perform life-saving hemodialysis (HD); however, the HD access portal is extremely vulnerable to infection, stenosis, and thrombo- occlusion. While vascular access options include the placement of central veinous catheters, arteriovenous (AV) fistulas, and AV grafts, superior outcomes have been established with the use of AV fistulas (AVFs). Despite national vascular access guidelines promoting the use of AVFs over synthetic arteriovenous grafts (AVGs) for dialysis due to their lower occlusion rates and longer survival, AVGs are still utilized in ~17% of all chronic HD patients (~85,000 in the U.S.). Regrettably, significant healthcare disparities exist within this patient population. Indeed, in chronic HD patients, the rate of AVG use is 77% higher in the Black/African American versus white population, while AVG use among females is 69% greater than in males. Thus, an important unmet need exists to address AVG patency and longevity. This SBIR Fast-Track project directly addresses the critical need by developing a unique antithrombotic agent, AB023 (xisomab 3G3), to help maintain chronic AVG access patency. To this end, we have recently completed a single-dose pilot phase 2a clinical trial (NCT03963895) in ESRD patients to evaluate whether this approach may be safe and effective. Our early clinical data suggests that xisomab 3G3 is indeed safe in this medically complex patient population, with no drug-related adverse events and no increased bleeding observed at the vascular access site (Lorentz, et. al. Blood, 2021). A single dose of xisomab 3G3 limited systemic markers of both thrombosis and inflammation, and also reduced severe dialysis circuit blood clotting events. During this proposed Phase I/II SBIR project, we propose to extend these studies into repeat, every other week drug administration to determine if this new approach to anticoagulation is safe and effective in chronic HD patients with AVGs, who generally have an elevated risk of both thrombosis and bleeding and no satisfactory options for therapeutic anticoagulation. Since xisomab 3G3 specifically targets coagulation factor XI (FXI) activation by factor XII (FXII) without inhibiting the FXI feedback activation by thrombin, our innovative drug candidate is entirely unique in the growing armamentarium of FXI inhibitors under development. Accordingly, since FXII deficiency in humans does not result in any known bleeding side-effects, xisomab 3G3 could be an effective antithrombotic strategy that is exceptionally safe. As such, xisomab 3G3 represents a fundamentally unique anticoagulation concept. Success of the proposed research and achievement of our critical milestones will lead directly to subsequent and definitive safety/efficacy trials in ESRD patients with chronically implanted AVGs, who are in desperate need of safe thromboprophylaxis.
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Thrombopoietin Targeting in Myeloproliferative Neoplasms
  • 批准号:
    10731078
  • 项目类别:
  • 资助金额:
    $70.03万
  • 财政年份:
    2022
  • 负责人:
    Christina U Lorentz
  • 依托单位:
Thrombopoietin Targeting in Myeloproliferative Neoplasms
  • 批准号:
    10484073
  • 项目类别:
  • 资助金额:
    $30.18万
  • 财政年份:
    2022
  • 负责人:
    Christina U Lorentz
  • 依托单位:
Factor XII Inhibitor for Surface Initiated Thrombosis
  • 批准号:
    10407510
  • 项目类别:
  • 资助金额:
    $95.35万
  • 财政年份:
    2016
  • 负责人:
    Christina U Lorentz
  • 依托单位:
Factor XII Inhibitor for Surface Initiated Thrombosis
  • 批准号:
    10170412
  • 项目类别:
  • 资助金额:
    $98.2万
  • 财政年份:
    2016
  • 负责人:
    Christina U Lorentz
  • 依托单位:
海外基金