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

Septic Shock Clinical Trial

Official title:

A Phase II, Multicentre, Randomised, Double-Blind, Placebo-Controlled, Dose Escalation Study to Assess the Safety, Tolerability and Pharmacokinetics of Intravenous Infusions of AZD9773 (CytoFab™) in Japanese Patients With Severe Sepsis and/or Septic Shock

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01144624
• Other study ID #: D0620C00005
• Status: Completed
• Phase: Phase 2
• First received: June 7, 2010
• Last updated: September 26, 2014
• Start date: July 2010
• Est. completion date: August 2011

Study information

• Verified date: September 2014
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: August 2011
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Sepsis
• Septic Shock
• Severe Sepsis
• Shock
• Shock, Septic

Intervention

Drug:
• AZD9773
A single loading dose followed by 9 maintenance doses; doses to be given every 12 hours over a period of 5 days
• Placebo
Intravenous infusion of a saline solution

Locations

Country	Name	City	State
Japan	Research Site	Hachioji	Tokyo
Japan	Research Site	Kobe	Hyogo
Japan	Research Site	Kumamoto-Shi	Kumamoto
Japan	Research Site	Ohta-ku	Tokyo
Japan	Research Site	Osaka
Japan	Research Site	Sapporo-shi	Hokkaido
Japan	Research Site	Sumiyoshi-ku	Osaka

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and Tolerability of AZD9773	Number of patients with treatment-emergent adverse events and number of patients who died over 28 days	28 day study period	Yes
Primary	Pharmacokinetics of AZD9773	Maximum concentration at steady state (Cmax ss) for serum total and specific fabs	From first dose to last dose (Day 5/6 or at premature treatment discontinuation)	No
Secondary	Pharmacodynamic Effects of AZD9773 on TNF-alpha	TNF-alpha levels over approximately 6 days following the first dose	Levels taken at baseline, over the dosing period (up to Day 5/6)	No

External Links

•   D0620C00005 Study Report Synopsis
•   redacted-CSP-D0620C00005.pdf