AZD9773 Dose Escalation Study

NCT00615017 | Completed Phase 2 Results DMC

• 1 other identifier: D0620C00004
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 26

Brief 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.

Conditions

Severe Sepsis

Keywords

Sepsis; septic shock; Systemic Inflammatory Response Syndrome

Outcome Measures

Primary Outcomes (12)

• Change From Baseline in Creatinine Values

  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

  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

  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

  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

  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

  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

  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

  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

  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.

  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

  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

  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

Secondary Outcomes (12)

• 28-Day Mortality

  End of study (Day 28)

• Change From Baseline in Sequential Organ Failure Assessment (SOFA) Scores

  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)

  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)

  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)

  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]

Study Arms (6)

AZD9773 cohort 1 (50 units/kg)

EXPERIMENTAL

AZD9773: single infusion of 50 units/kg

Drug: AZD9773 (CytoFab)

AZD9773 cohort 2 (250 units/kg)

EXPERIMENTAL

AZD9773: single infusion of 250 units/kg

Drug: AZD9773 (CytoFab)

AZD9773 cohort 3 (250/50 units/kg)

EXPERIMENTAL

AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs

Drug: AZD9773 (CytoFab)

AZD9773 cohort 4 (500/100 units/kg)

EXPERIMENTAL

AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs

Drug: AZD9773 (CytoFab)

AZD9773 cohort 5 (750/250 units/kg)

EXPERIMENTAL

AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs

Drug: AZD9773 (CytoFab)

Placebo

PLACEBO COMPARATOR

Placebo

Other: Placebo

Interventions

AZD9773 (CytoFab) DRUG

intravenous infusions

AZD9773 cohort 1 (50 units/kg); AZD9773 cohort 2 (250 units/kg); AZD9773 cohort 3 (250/50 units/kg); AZD9773 cohort 4 (500/100 units/kg); AZD9773 cohort 5 (750/250 units/kg)

Placebo OTHER

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (26)

Research Site

Birmingham, Alabama, United States

Location

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Newark, Delaware, United States

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Bay Pines, Florida, United States

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Miami, Florida, United States

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Chicago, Illinois, United States

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Oak Park, Illinois, United States

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Peoria, Illinois, United States

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Indianapolis, Indiana, United States

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Iowa City, Iowa, United States

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Hazard, Kentucky, United States

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Lexington, Kentucky, United States

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Baltimore, Maryland, United States

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Kansas City, Missouri, United States

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Camden, New Jersey, United States

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Newark, New Jersey, United States

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Brooklyn, New York, United States

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New York, New York, United States

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Rochester, New York, United States

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Durham, North Carolina, United States

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Greensboro, North Carolina, United States

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Winston-Salem, North Carolina, United States

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Columbus, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Nashville, Tennessee, United States

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Galveston, Texas, United States

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Research Site

Houston, Texas, United States

Location

Related Publications (1)

• Yates JW, Das S, Mainwaring G, Kemp J. Population pharmacokinetic/pharmacodynamic modelling of the anti-TNF-alpha polyclonal fragment antibody AZD9773 in patients with severe sepsis. J Pharmacokinet Pharmacodyn. 2012 Dec;39(6):591-9. doi: 10.1007/s10928-012-9270-4. Epub 2012 Sep 23.

  PMID: 23001587 DERIVED

MeSH Terms

Conditions

Sepsis; Shock, Septic; Systemic Inflammatory Response Syndrome

Interventions

AZD9773; CytoFab

Condition Hierarchy (Ancestors)

Infections; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Results Point of Contact

• Title: Justin Lindemann
• Organization: AstraZeneca

ClinicalTrialTransparency@astrazeneca.com

Study Officials

• Steven Simonson, MD

  AstraZeneca

  STUDY DIRECTOR

• Wayne Dankner, MD

  Parexel

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2008
• First Posted: February 14, 2008
• Study Start: January 1, 2008
• Primary Completion: July 1, 2009
• Study Completion: July 1, 2009
• Last Updated: August 22, 2013
• Results First Posted: August 22, 2013

Record last verified: 2013-07

Locations

US (26)