AZD9773 Dose Escalation Study

AstraZeneca

Status and phase: Completed; Phase 2

Conditions: Severe Sepsis

Treatments: Other: Placebo; Drug: AZD9773 (CytoFab)

Study type: Interventional

Funder types: Industry

Identifiers

NCT00615017

D0620C00004

Details and patient eligibility

About

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.

Enrollment: 70 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: Triple Blind

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70 participants in 6 patient groups, including a placebo group

AZD9773 cohort 1 (50 units/kg)

Experimental group

Description:

AZD9773: single infusion of 50 units/kg

Treatment:

Drug: AZD9773 (CytoFab)

AZD9773 cohort 2 (250 units/kg)

Experimental group

Description:

AZD9773: single infusion of 250 units/kg

Treatment:

Drug: AZD9773 (CytoFab)

AZD9773 cohort 3 (250/50 units/kg)

Experimental group

Description:

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

Treatment:

Drug: AZD9773 (CytoFab)

AZD9773 cohort 4 (500/100 units/kg)

Experimental group

Description:

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

Treatment:

Drug: AZD9773 (CytoFab)

AZD9773 cohort 5 (750/250 units/kg)

Experimental group

Description:

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

Treatment:

Drug: AZD9773 (CytoFab)

Placebo

Placebo Comparator group

Description:

Placebo

Treatment:

Other: Placebo