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AZD9773 Dose Escalation Study

19. července 2013 aktualizováno: AstraZeneca

A Placebo-controlled, Double-blind, Dose-escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics and Pharmacodynamics of Single and Multiple Intravenous Infusions of CytoFab (AZD9773) in Patients With Severe Sepsis

This is a double-blind, placebo-controlled, multi-center, dose-escalation study to assess the safety, tolerability, Pharmacokinetics and Pharmacodynamics of single and multiple ascending intravenous infusions of CytoFab (AZD9773) in adult patients with severe sepsis.

Přehled studie

Postavení

Dokončeno

Podmínky

Intervence / Léčba

Typ studie

Intervenční

Zápis (Aktuální)

70

Fáze

  • Fáze 2

Kontakty a umístění

Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.

Studijní místa

  • Spojené státy
    • Alabama
      • Birmingham, Alabama, Spojené státy
        • Research Site
    • Delaware
      • Newark, Delaware, Spojené státy
        • Research Site
    • Florida
      • Bay Pines, Florida, Spojené státy
        • Research Site
      • Miami, Florida, Spojené státy
        • Research Site
    • Illinois
      • Chicago, Illinois, Spojené státy
        • Research Site
      • Oak Park, Illinois, Spojené státy
        • Research Site
      • Peoria, Illinois, Spojené státy
        • Research Site
    • Indiana
      • Indianapolis, Indiana, Spojené státy
        • Research Site
    • Iowa
      • Iowa City, Iowa, Spojené státy
        • Research Site
    • Kentucky
      • Hazard, Kentucky, Spojené státy
        • Research Site
      • Lexington, Kentucky, Spojené státy
        • Research Site
    • Maryland
      • Baltimore, Maryland, Spojené státy
        • Research Site
    • Missouri
      • Kansas City, Missouri, Spojené státy
        • Research Site
    • New Jersey
      • Camden, New Jersey, Spojené státy
        • Research Site
      • Newark, New Jersey, Spojené státy
        • Research Site
    • New York
      • Brooklyn, New York, Spojené státy
        • Research Site
      • New York, New York, Spojené státy
        • Research Site
      • Rochester, New York, Spojené státy
        • Research Site
    • North Carolina
      • Durham, North Carolina, Spojené státy
        • Research Site
      • Greensboro, North Carolina, Spojené státy
        • Research Site
      • Winston Salem, North Carolina, Spojené státy
        • Research Site
    • Ohio
      • Columbus, Ohio, Spojené státy
        • Research Site
    • Oklahoma
      • Oklahoma City, Oklahoma, Spojené státy
        • Research Site
    • Tennessee
      • Nashville, Tennessee, Spojené státy
        • Research Site
    • Texas
      • Galveston, Texas, Spojené státy
        • Research Site
      • Houston, Texas, Spojené státy
        • Research Site

Kritéria účasti

Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.

Kritéria způsobilosti

Věk způsobilý ke studiu

18 let a starší (Dospělý, Starší dospělý)

Přijímá zdravé dobrovolníky

Ne

Pohlaví způsobilá ke studiu

Všechno

Popis

Inclusion Criteria:

  • Clinical evidence of infection requiring treatment with parenteral antibiotics
  • Patients must meet multiple Systemic Inflammatory Response Syndrome (SIRS) criteria
  • Patients must meet criteria for cardiovascular and/or respiratory dysfunction
  • Sepsis (infection plus SIRS criteria) must be present prior to organ dysfunction

Exclusion Criteria:

  • Moribund and death is considered imminent, or patient not expected to survive 90 days because of underlying medical condition, or classified as Do Not Resuscitate or Do Not Treat
  • Patient cannot attain a MAP >60 mmHg when measured via an arterial line and/or a Systolic Blood Pressure (SBP) >80 mmHg in the presence of vasopressors and iv fluids for a period of ≥2 hours
  • Receiving immunosuppressants, or high dose steroids within 2 months of provision of informed consent
  • Any history of hypersensitivity reaction to sheep products, latex, papain or papaya, or chymopapain or previously administered antivenom manufactured using ovine serum, digoxin immune fab (DigiFab™ , DIGIBIND® ), crotalidae polyvalent immune fab (ovine) (CroFab™ ), or other sheep derived product.
  • Treatment with anti Tumor-Necrosis-Factor (anti-TNF) antibodies within 8 weeks before provision of written informed consent.

Studijní plán

Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.

Jak je studie koncipována?

Detaily designu

  • Primární účel: Léčba
  • Přidělení: Randomizované
  • Intervenční model: Přiřazení jedné skupiny
  • Maskování: Trojnásobný

Zbraně a zásahy

Skupina účastníků / Arm
Intervence / Léčba
Komparátor placeba: Placebo
Jiný: Placebo
Placebo
Experimentální: AZD9773 cohort 1 (50 units/kg)
AZD9773: single infusion of 50 units/kg
Lék: AZD9773 (CytoFab)
intravenous infusions
Experimentální: AZD9773 cohort 2 (250 units/kg)
AZD9773: single infusion of 250 units/kg
Lék: AZD9773 (CytoFab)
intravenous infusions
Experimentální: AZD9773 cohort 3 (250/50 units/kg)
AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs
Lék: AZD9773 (CytoFab)
intravenous infusions
Experimentální: AZD9773 cohort 4 (500/100 units/kg)
AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs
Lék: AZD9773 (CytoFab)
intravenous infusions
Experimentální: AZD9773 cohort 5 (750/250 units/kg)
AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs
Lék: AZD9773 (CytoFab)
intravenous infusions

Co je měření studie?

Primární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Change From Baseline in Creatinine Values
Časové okno: End of study (Day 28)
Change in creatinine values from baseline (pre-infusion) to follow-up (28 days after the start of study drug administration) [calculated as Day 28 mean minus baseline mean]. Safety analysis set (ie all patients who started study drug infusion).
End of study (Day 28)
Change From Baseline in Alanine Aminotransferase Values
Časové okno: End of study (Day 28)
Change in alanine aminotransferase values from baseline (pre-infusion) to follow-up (28 days after the start of study drug administration) [calculated as Day 28 mean minus baseline mean]. Safety analysis set (ie all patients who started study drug infusion).
End of study (Day 28)
Change From Baseline in Aspartate Aminotransferase Values
Časové okno: End of study (Day 28)
Change in aspartate aminotransferase values from baseline (pre-infusion) to follow-up (28 days after the start of study drug administration) [calculated as Day 28 mean minus baseline mean]. Safety analysis set (ie all patients who started study drug infusion).
End of study (Day 28)
Change From Baseline in Bilirubin Values
Časové okno: End of study (Day 28)
Change in bilirubin values from baseline (pre-infusion) to follow-up (28 days after the start of study drug administration) [calculated as Day 28 mean minus baseline mean]. Safety analysis set (ie all patients who started study drug infusion).
End of study (Day 28)
Change From Baseline in Haemoglobin Values
Časové okno: End of study (Day 28)
Change in haemoglobin values from baseline (pre-infusion) to follow-up (28 days after the start of study drug administration) [calculated as Day 28 mean minus baseline mean]. Safety analysis set (ie all patients who started study drug infusion).
End of study (Day 28)
Change From Baseline in White Blood Cell Values
Časové okno: End of study (Day 28)
Change in white blood cell values from baseline (pre-infusion) to follow-up (28 days after the start of study drug administration) [calculated as Day 28 mean minus baseline mean]. Safety analysis set (ie all patients who started study drug infusion).
End of study (Day 28)
Change From Baseline in Platelet Count Values
Časové okno: End of study (Day 28)
Change in platelet count values from baseline (pre-infusion) to follow-up (28 days after the start of study drug administration) [calculated as Day 28 mean minus baseline mean]. Safety analysis set (ie all patients who started study drug infusion).
End of study (Day 28)
Change From Baseline in Prothrombin Time Values
Časové okno: Day 7
Change in prothrombin time values from baseline (pre-infusion) to Day 7 [calculated as Day 7 mean minus baseline mean]. Safety analysis set (ie all patients who started study drug infusion).
Day 7
Change From Baseline in Troponin I
Časové okno: Day 6
Change in troponin I values from baseline (pre-infusion) to Day 6 [calculated as Day 6 mean minus baseline mean]. Safety analysis set (ie all patients who started study drug infusion).
Day 6
Change From Baseline in QT With Fridericia Correction (QTcF), Where QT is Measured by ECG, and is the Time Interval Between the Start of the Q Wave and the End of the T Wave in the Heart's Electrical Cycle.
Časové okno: Day 1 (end of infusion) for Cohorts 1 and 2; Day 5 (end of infusion) for Cohorts 3 to 5 and placebo
Change in QTcF from baseline (pre-infusion) to Day 1 (end of infusion) for Cohorts 1 and 2 [calculated as Day 1 mean minus baseline mean] and Day 5 (end of infusion) for Cohorts 3 to 5 and placebo [calculated as Day 5 mean minus baseline mean]. Safety analysis set (ie all patients who started study drug infusion).
Day 1 (end of infusion) for Cohorts 1 and 2; Day 5 (end of infusion) for Cohorts 3 to 5 and placebo
Change From Baseline in Calculated Mean Arterial Blood Pressure
Časové okno: Day 14
Change in calculated mean arterial pressure from baseline (pre-infusion) to Day 14 [calculated as Day 14 mean minus baseline mean]. Safety analysis set (ie all patients who started study drug infusion).
Day 14
Change From Baseline in Body Weight
Časové okno: Day 6
Change in body weight from baseline (pre-infusion) to Day 6 [calculated as Day 6 mean minus baseline mean]. Safety analysis set (ie all patients who started study drug infusion).
Day 6

Sekundární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
28-Day Mortality
Časové okno: End of study (Day 28)
The number of patients who had died at Day 28. Safety analysis set (ie all patients who started study drug infusion).
End of study (Day 28)
Change From Baseline in Sequential Organ Failure Assessment (SOFA) Scores
Časové okno: Day 6
Change in SOFA (Sequential Organ Failure Assessment) scores from baseline (pre-infusion) to Day 6 [calculated as Day 6 mean minus baseline mean]. The SOFA score is out of a maximum of 24 (units on a scale 0 to 24). The higher the score, the worse the organ system functioning. Safety analysis set (ie all patients who started study drug infusion).
Day 6
Area Under the Serum Concentration-time Curve From 0 to 12 Hours (AUC(0-12)) of Single Dose AZD9773 Serum Total Fabs (Cohorts 1 and 2)
Časové okno: Day 1 [PK samples taken pre-dose, the end of each infusion rate and then at 0.5, 1, 2, 8, and 12h post-(last) infusion]
AUC(0-12) for single dose AZD9773 serum total Fabs (cohorts 1 and 2). PK analysis set (ie a subset of the safety analysis set including only those patients without important deviations that could affect the PK).
Day 1 [PK samples taken pre-dose, the end of each infusion rate and then at 0.5, 1, 2, 8, and 12h post-(last) infusion]
Terminal Half-life (t1/2) of Single Dose AZD9773 Serum Total Fabs (Cohorts 1 and 2)
Časové okno: Day 1 [PK samples taken pre-dose, the end of each infusion rate and then at 0.5, 1, 2, 8, 12, 24, 48, and 72 h post-(last) infusion]
t1/2 of single dose AZD9773 serum total Fabs (cohorts 1 and 2). PK analysis set (ie a subset of the safety analysis set including only those patients without important deviations that could affect the PK).
Day 1 [PK samples taken pre-dose, the end of each infusion rate and then at 0.5, 1, 2, 8, 12, 24, 48, and 72 h post-(last) infusion]
Total Apparent Clearance (CL) of Single Dose AZD9773 Serum Total Fabs (Cohorts 1 and 2)
Časové okno: Day 1 [PK samples taken pre-dose, the end of each infusion rate and then at 0.5, 1, 2, 8, 12, 24, 48, and 72 h post-(last) infusion]
CL of single dose AZD9773 serum total Fabs (cohorts 1 and 2). PK analysis set (ie a subset of the safety analysis set including only those patients without important deviations that could affect the PK).
Day 1 [PK samples taken pre-dose, the end of each infusion rate and then at 0.5, 1, 2, 8, 12, 24, 48, and 72 h post-(last) infusion]
AUC(0-12) of Loading Dose AZD9773 Serum Total Fabs (Cohorts 3, 4 and 5)
Časové okno: Day 1 [PK samples taken pre-dose, the end of each infusion rate and then at 0.5, 1, 2, 8 and 12 h post-(last) infusion]
AUC(0-12) of loading dose AZD9773 serum total Fabs (cohorts 3, 4 and 5). PK analysis set (ie a subset of the safety analysis set including only those patients without important deviations that could affect the PK).
Day 1 [PK samples taken pre-dose, the end of each infusion rate and then at 0.5, 1, 2, 8 and 12 h post-(last) infusion]
Maximum (End of Infusion) Serum Concentration (Cinf) of Loading Dose AZD9773 Serum Total Fabs (Cohorts 3,4 and 5)
Časové okno: Day 1 [PK samples taken pre-dose, the end of each infusion rate and then at 0.5, 1, 2, 8 and 12 h post-(last)infusion]
Cinf of loading dose AZD9773 serum total Fabs (cohorts 3, 4 and 5). PK analysis set (ie a subset of the safety analysis set including only those patients without important deviations that could affect the PK).
Day 1 [PK samples taken pre-dose, the end of each infusion rate and then at 0.5, 1, 2, 8 and 12 h post-(last)infusion]
Time to Reach Cinf (Tmax) of Loading Dose AZD9773 Serum Total Fabs (Cohorts 3, 4 and 5)
Časové okno: Day 1 [PK samples taken pre-dose, the end of each infusion rate and then at 0.5, 1, 2, 8 and 12 h post-(last)infusion]
tmax of loading dose AZD9773 serum total Fabs (cohorts 3, 4 and 5). PK analysis set (ie a subset of the safety analysis set including only those patients without important deviations that could affect the PK).
Day 1 [PK samples taken pre-dose, the end of each infusion rate and then at 0.5, 1, 2, 8 and 12 h post-(last)infusion]
AUC(0-12) of Maintenance Dose AZD9773 Serum Total Fabs (Cohorts 3, 4 and 5)
Časové okno: PK samples taken pre-dose of Doses 5,7 and 9, then at 0, 0.5, 1, 2, 8 and 12 h post dose 9 infusion
AUC(0-12) of maintenance dose AZD9773 serum total Fabs (cohorts 3, 4 and 5). PK analysis set (ie a subset of the safety analysis set including only those patients without important deviations that could affect the PK).
PK samples taken pre-dose of Doses 5,7 and 9, then at 0, 0.5, 1, 2, 8 and 12 h post dose 9 infusion
Cinf of Maintenance Dose AZD9773 Serum Total Fabs (Cohorts 3, 4 and 5)
Časové okno: PK samples taken pre-dose of Doses 5,7 and 9, then at 0, 0.5, 1, 2, 8 and 12 h post dose 9 infusion
Cinf of maintenance dose AZD9773 serum total Fabs (cohorts 3, 4 and 5). PK analysis set (ie a subset of the safety analysis set including only those patients without important deviations that could affect the PK).
PK samples taken pre-dose of Doses 5,7 and 9, then at 0, 0.5, 1, 2, 8 and 12 h post dose 9 infusion
Tmax of Maintenance Dose AZD9773 Serum Total Fabs (Cohorts 3, 4 and 5)
Časové okno: PK samples taken pre-dose of Doses 5,7 and 9, then at 0, 0.5, 1, 2, 8 and 12 h post dose 9 infusion
tmax of maintenance dose AZD9773 serum total Fabs (cohorts 3, 4 and 5). PK analysis set (ie a subset of the safety analysis set including only those patients without important deviations that could affect the PK).
PK samples taken pre-dose of Doses 5,7 and 9, then at 0, 0.5, 1, 2, 8 and 12 h post dose 9 infusion
Number of Patients Below Tumour Necrosis Factor (TNF)-Alpha Limit of Quantification (LOQ) at 24 Hours (n< LOQ)
Časové okno: 24 hours
Number of patients below tumour necrosis factor (TNF)-alpha limit of quantification (LOQ) at 24 hours (n< LOQ) measured by ELISA (LOQ = 1.3 pg/mL). Safety analysis set (ie all patients who started study drug infusion).
24 hours

Spolupracovníci a vyšetřovatelé

Zde najdete lidi a organizace zapojené do této studie.

Sponzor

AstraZeneca

Vyšetřovatelé

  • Ředitel studie: Steven Simonson, MD, AstraZeneca

Publikace a užitečné odkazy

Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.

Obecné publikace

Termíny studijních záznamů

Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.

Hlavní termíny studia

Začátek studia

1. ledna 2008

Primární dokončení (Aktuální)

1. července 2009

Dokončení studie (Aktuální)

1. července 2009

Termíny zápisu do studia

První předloženo

31. ledna 2008

První předloženo, které splnilo kritéria kontroly kvality

1. února 2008

První zveřejněno (Odhad)

14. února 2008

Aktualizace studijních záznamů

Poslední zveřejněná aktualizace (Odhad)

22. srpna 2013

Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality

19. července 2013

Naposledy ověřeno

1. července 2013

Více informací

Termíny související s touto studií

Klíčová slova

Další relevantní podmínky MeSH

Další identifikační čísla studie

  • D0620C00004

Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .

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