AZD9773 Dose Escalation Study
19. juli 2013 oppdatert av: 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.
Studieoversikt
Status
Fullført
Forhold
Intervensjon / Behandling
Studietype
Intervensjonell
Registrering (Faktiske)
70
Fase
- Fase 2
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
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Alabama
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Birmingham, Alabama, Forente stater
- Research Site
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Delaware
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Newark, Delaware, Forente stater
- Research Site
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Florida
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Bay Pines, Florida, Forente stater
- Research Site
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Miami, Florida, Forente stater
- Research Site
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Illinois
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Chicago, Illinois, Forente stater
- Research Site
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Oak Park, Illinois, Forente stater
- Research Site
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Peoria, Illinois, Forente stater
- Research Site
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Indiana
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Indianapolis, Indiana, Forente stater
- Research Site
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Iowa
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Iowa City, Iowa, Forente stater
- Research Site
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Kentucky
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Hazard, Kentucky, Forente stater
- Research Site
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Lexington, Kentucky, Forente stater
- Research Site
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Maryland
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Baltimore, Maryland, Forente stater
- Research Site
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Missouri
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Kansas City, Missouri, Forente stater
- Research Site
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New Jersey
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Camden, New Jersey, Forente stater
- Research Site
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Newark, New Jersey, Forente stater
- Research Site
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New York
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Brooklyn, New York, Forente stater
- Research Site
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New York, New York, Forente stater
- Research Site
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Rochester, New York, Forente stater
- Research Site
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North Carolina
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Durham, North Carolina, Forente stater
- Research Site
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Greensboro, North Carolina, Forente stater
- Research Site
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Winston Salem, North Carolina, Forente stater
- Research Site
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Ohio
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Columbus, Ohio, Forente stater
- Research Site
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Oklahoma
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Oklahoma City, Oklahoma, Forente stater
- Research Site
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Tennessee
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Nashville, Tennessee, Forente stater
- Research Site
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Texas
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Galveston, Texas, Forente stater
- Research Site
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Houston, Texas, Forente stater
- Research Site
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Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
18 år og eldre (Voksen, Eldre voksen)
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
Alle
Beskrivelse
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.
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Trippel
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
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Placebo komparator: Placebo
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Placebo
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Eksperimentell: AZD9773 cohort 1 (50 units/kg)
AZD9773: single infusion of 50 units/kg
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intravenous infusions
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Eksperimentell: AZD9773 cohort 2 (250 units/kg)
AZD9773: single infusion of 250 units/kg
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intravenous infusions
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Eksperimentell: AZD9773 cohort 3 (250/50 units/kg)
AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs
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intravenous infusions
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Eksperimentell: AZD9773 cohort 4 (500/100 units/kg)
AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs
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intravenous infusions
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Eksperimentell: AZD9773 cohort 5 (750/250 units/kg)
AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs
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intravenous infusions
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Change From Baseline in Creatinine Values
Tidsramme: End of study (Day 28)
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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).
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End of study (Day 28)
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Change From Baseline in Alanine Aminotransferase Values
Tidsramme: End of study (Day 28)
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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).
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End of study (Day 28)
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Change From Baseline in Aspartate Aminotransferase Values
Tidsramme: End of study (Day 28)
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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).
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End of study (Day 28)
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Change From Baseline in Bilirubin Values
Tidsramme: End of study (Day 28)
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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).
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End of study (Day 28)
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Change From Baseline in Haemoglobin Values
Tidsramme: End of study (Day 28)
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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).
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End of study (Day 28)
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Change From Baseline in White Blood Cell Values
Tidsramme: End of study (Day 28)
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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).
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End of study (Day 28)
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Change From Baseline in Platelet Count Values
Tidsramme: End of study (Day 28)
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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).
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End of study (Day 28)
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Change From Baseline in Prothrombin Time Values
Tidsramme: Day 7
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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).
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Day 7
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Change From Baseline in Troponin I
Tidsramme: Day 6
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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).
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Day 6
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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.
Tidsramme: Day 1 (end of infusion) for Cohorts 1 and 2; Day 5 (end of infusion) for Cohorts 3 to 5 and placebo
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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).
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Day 1 (end of infusion) for Cohorts 1 and 2; Day 5 (end of infusion) for Cohorts 3 to 5 and placebo
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Change From Baseline in Calculated Mean Arterial Blood Pressure
Tidsramme: Day 14
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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).
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Day 14
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Change From Baseline in Body Weight
Tidsramme: Day 6
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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).
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Day 6
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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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28-Day Mortality
Tidsramme: End of study (Day 28)
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The number of patients who had died at Day 28.
Safety analysis set (ie all patients who started study drug infusion).
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End of study (Day 28)
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Change From Baseline in Sequential Organ Failure Assessment (SOFA) Scores
Tidsramme: Day 6
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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).
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Day 6
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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)
Tidsramme: 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]
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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).
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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]
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Terminal Half-life (t1/2) of Single Dose AZD9773 Serum Total Fabs (Cohorts 1 and 2)
Tidsramme: 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]
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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).
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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]
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Total Apparent Clearance (CL) of Single Dose AZD9773 Serum Total Fabs (Cohorts 1 and 2)
Tidsramme: 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]
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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).
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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]
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AUC(0-12) of Loading Dose AZD9773 Serum Total Fabs (Cohorts 3, 4 and 5)
Tidsramme: 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]
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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).
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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]
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Maximum (End of Infusion) Serum Concentration (Cinf) of Loading Dose AZD9773 Serum Total Fabs (Cohorts 3,4 and 5)
Tidsramme: 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]
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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).
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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]
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Time to Reach Cinf (Tmax) of Loading Dose AZD9773 Serum Total Fabs (Cohorts 3, 4 and 5)
Tidsramme: 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]
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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]
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AUC(0-12) of Maintenance Dose AZD9773 Serum Total Fabs (Cohorts 3, 4 and 5)
Tidsramme: 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
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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
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Cinf of Maintenance Dose AZD9773 Serum Total Fabs (Cohorts 3, 4 and 5)
Tidsramme: 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
|
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Tmax of Maintenance Dose AZD9773 Serum Total Fabs (Cohorts 3, 4 and 5)
Tidsramme: 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
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Number of Patients Below Tumour Necrosis Factor (TNF)-Alpha Limit of Quantification (LOQ) at 24 Hours (n< LOQ)
Tidsramme: 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
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Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Etterforskere
- Studieleder: Steven Simonson, MD, AstraZeneca
Publikasjoner og nyttige lenker
Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart
1. januar 2008
Primær fullføring (Faktiske)
1. juli 2009
Studiet fullført (Faktiske)
1. juli 2009
Datoer for studieregistrering
Først innsendt
31. januar 2008
Først innsendt som oppfylte QC-kriteriene
1. februar 2008
Først lagt ut (Anslag)
14. februar 2008
Oppdateringer av studieposter
Sist oppdatering lagt ut (Anslag)
22. august 2013
Siste oppdatering sendt inn som oppfylte QC-kriteriene
19. juli 2013
Sist bekreftet
1. juli 2013
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- D0620C00004
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