Phase 2
Completed N=70
AZD9773 Dose Escalation Study
Severe Sepsis
Source: ClinicalTrials.gov NCT00615017 ↗
Enrolled (actual)
70
Serious AEs
51.4%
Results posted
Aug 2013
Primary outcomePrimary: Change From Baseline in Creatinine Values — -78.6; -196.8; -25.1; -10.9 μmol/L
Summary
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in Creatinine Values |
-78.6; -196.8; -25.1; -10.9; 159.0; -57.4 | — |
| PRIMARY Change From Baseline in Alanine Aminotransferase Values |
-0.998; 0.017; -3.133; -0.520; -0.825; -0.111 | — |
| PRIMARY Change From Baseline in Aspartate Aminotransferase Values |
-2.298; -0.213; -3.647; -0.926; -0.998; -0.253 | — |
| PRIMARY Change From Baseline in Bilirubin Values |
-11.30; -13.10; -10.04; -23.71; -2.58; -10.00 | — |
| PRIMARY Change From Baseline in Haemoglobin Values |
7; -16.3; -0.8; 6.5; -13.8; -4.5 | — |
| PRIMARY Change From Baseline in White Blood Cell Values |
-17.552; -8.975; 0.413; -0.225; -3.482; -9.987 | — |
| PRIMARY Change From Baseline in Platelet Count Values |
287; 117.3; 162; 72.3; 252.5; 145.1 | — |
| PRIMARY Change From Baseline in Prothrombin Time Values |
-3.20; 0.53; -1.00; -5.31; 4.36; 1.68 | — |
| PRIMARY Change From Baseline in Troponin I |
-16.454; -9.523; -0.630; -1.434; -0.027; -0.735 | — |
| PRIMARY 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. |
-9.9; 3.6; -21.5; -9.2; 21.4; -3.4 | — |
| PRIMARY Change From Baseline in Calculated Mean Arterial Blood Pressure |
20; 7.3; 5.3; 28.7; 6.8; 18 | — |
| PRIMARY Change From Baseline in Body Weight |
1.3; 0.2; 4; 7.4; 0.2; 9.9 | — |
| SECONDARY 28-Day Mortality |
2; 4; 5; 1; 1; 6 | — |
| SECONDARY Change From Baseline in Sequential Organ Failure Assessment (SOFA) Scores |
-6; -2; -3.3; -3; -6; -4.3 | — |
| SECONDARY 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) |
125.22; 581.01 | — |
| SECONDARY Terminal Half-life (t1/2) of Single Dose AZD9773 Serum Total Fabs (Cohorts 1 and 2) |
17.97; 19.76 | — |
| SECONDARY Total Apparent Clearance (CL) of Single Dose AZD9773 Serum Total Fabs (Cohorts 1 and 2) |
6.11; 7.61 | — |
| SECONDARY AUC(0-12) of Loading Dose AZD9773 Serum Total Fabs (Cohorts 3, 4 and 5) |
449.18; 691.53; 1872.73 | — |
| SECONDARY Maximum (End of Infusion) Serum Concentration (Cinf) of Loading Dose AZD9773 Serum Total Fabs (Cohorts 3,4 and 5) |
107.84; 160.09; 351.52 | — |
| SECONDARY Time to Reach Cinf (Tmax) of Loading Dose AZD9773 Serum Total Fabs (Cohorts 3, 4 and 5) |
0.92; 1.08; 1.12 | — |
| SECONDARY AUC(0-12) of Maintenance Dose AZD9773 Serum Total Fabs (Cohorts 3, 4 and 5) |
162.82; 251.59; 980.95 | — |
| SECONDARY Cinf of Maintenance Dose AZD9773 Serum Total Fabs (Cohorts 3, 4 and 5) |
28.37; 42.51; 151.76 | — |
| SECONDARY Tmax of Maintenance Dose AZD9773 Serum Total Fabs (Cohorts 3, 4 and 5) |
0.54; 1.00; 0.74 | — |
| SECONDARY Number of Patients Below Tumour Necrosis Factor (TNF)-Alpha Limit of Quantification (LOQ) at 24 Hours (n< LOQ) |
1.0; 3.0; 5.0; 6.0; 4.0; 0.0 | — |
Eligibility Criteria
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.
Data sourced from ClinicalTrials.gov (NCT00615017). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.