A Study to Assess Safety,and Tolerability of 2 Doses of AZD9773 (CytoFab™) in Japanese With Severe Sepsis/Septic Shock

Phase 2

Completed

• Conditions: Severe Sepsis; Septic Shock
• Interventions: Drug: Placebo; Drug: AZD9773

• Registration Number: NCT01144624
• Lead Sponsor: AstraZeneca

Brief Summary

The two co-primary objectives of this study are to assess in Japanese patients with severe sepsis and/or septic shock: 1) the safety and tolerability of two different doses of intravenous AZD9773 and 2) the PK of AZD9773.

The secondary objective is to make a preliminary assessment of the pharmacodynamics of two different doses of intravenous AZD9773 in Japanese patients with severe sepsis and/or septic shock.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2010-06-07
• Study First Submitted QC: 2010-06-14
• Study First Posted: 2010-06-15
• Study Start: 2010-07
• Primary Completion: 2011-08
• Study Completion: 2011-08
• Results First Submitted: 2012-12-11
• Results First Submitted QC: 2013-07-19
• Results First Posted: 2013-08-22
• Status Verified: 2014-09
• Last Update Submitted: 2014-09-26
• Last Update Posted: 2014-10-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

• Japanese adults with a first episode of sepsis during this hospitalisation and objective evidence of infection that requires parenteral antibiotics.
• At least 2 of 4 SIRS criteria in the 24 hours before organ dysfunction (must include either fever OR elevated white blood cells [WBC])
• Cardiovascular or respiratory dysfunction.

Exclusion Criteria

• Immunocompromising comorbidities or concomitant medications:

  1. Advanced human immunodeficiency virus (HIV) infection (CD4 ≤50/mm3).
  2. Haemopoietic or lymphoreticular malignancies not in remission.
  3. Receiving radiation therapy or chemotherapy.
  4. Any organ or bone marrow transplant within the past 24 weeks.
  5. Absolute neutrophil count <500 per μL.
  6. High dose steroids or other immunocompromising drugs.

• Concomitant diseases:

  1. Deep-seated fungal infection or active tuberculosis.
  2. Severe chronic liver disease associated with portal hypertension, cirrhosis, chronic ascites or Child-Pugh class C.
  3. History of chronic hypercarbia, respiratory failure in past 6 months or use of home oxygen in the setting of severe chronic respiratory disease.
  4. Neuromuscular disorders that impact breathing/spontaneous ventilation.
  5. Quadriplegia.
  6. Cardiac arrest in the past 30 days.
  7. New York Heart Association functional Class III or IV due to heart failure or any disorder.
  8. Burns over > 30% of body surface area in the past 5 days.

• Medication and allergy disqualifications.

  1. Treatment with anti-TNF agents within the last 8 weeks.
  2. Previously received ovine derived products (CroFab™, DigiFab™).
  3. Sheep product allergy or allergy to papain, chymopapain.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2	Placebo	-
1	AZD9773	AZD9773 250 units/kg (1 infusion) + 50 units/kg (9 infusions) (Dose Cohort 1): AZD9773 500 units/kg (1 infusion) + 100 units/kg (9 infusions) (Dose Cohort 2)

Primary Outcome Measures

Name	Time	Method
Safety and Tolerability of AZD9773	28 day study period	Number of patients with treatment-emergent adverse events and number of patients who died over 28 days
Pharmacokinetics of AZD9773	From first dose to last dose (Day 5/6 or at premature treatment discontinuation)	Maximum concentration at steady state (Cmax ss) for serum total and specific fabs

Secondary Outcome Measures

Name	Time	Method
Pharmacodynamic Effects of AZD9773 on TNF-alpha	Levels taken at baseline, over the dosing period (up to Day 5/6)	TNF-alpha levels over approximately 6 days following the first dose

Trial Locations

Locations (1)

Research Site; 🇯🇵 Osaka, Japan