Back to resultsA Study to Assess Safety,and Tolerability of 2 Doses of AZD9773 (CytoFab™) in Japanese With Severe Sepsis/Septic Shock
Primary Purpose
Severe Sepsis, Septic Shock
Status
Completed
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
AZD9773
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Severe Sepsis focused on measuring TNF neutralisation
Eligibility Criteria
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:
- Advanced human immunodeficiency virus (HIV) infection (CD4 ≤50/mm3).
- Haemopoietic or lymphoreticular malignancies not in remission.
- Receiving radiation therapy or chemotherapy.
- Any organ or bone marrow transplant within the past 24 weeks.
- Absolute neutrophil count <500 per μL.
- High dose steroids or other immunocompromising drugs.
Concomitant diseases:
- Deep-seated fungal infection or active tuberculosis.
- Severe chronic liver disease associated with portal hypertension, cirrhosis, chronic ascites or Child-Pugh class C.
- History of chronic hypercarbia, respiratory failure in past 6 months or use of home oxygen in the setting of severe chronic respiratory disease.
- Neuromuscular disorders that impact breathing/spontaneous ventilation.
- Quadriplegia.
- Cardiac arrest in the past 30 days.
- New York Heart Association functional Class III or IV due to heart failure or any disorder.
- Burns over > 30% of body surface area in the past 5 days.
Medication and allergy disqualifications.
- Treatment with anti-TNF agents within the last 8 weeks.
- Previously received ovine derived products (CroFab™, DigiFab™).
- Sheep product allergy or allergy to papain, chymopapain.
Sites / Locations
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
1
2
Arm Description
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)
Outcomes
Primary Outcome Measures
Safety and Tolerability of AZD9773
Number of patients with treatment-emergent adverse events and number of patients who died over 28 days
Pharmacokinetics of AZD9773
Maximum concentration at steady state (Cmax ss) for serum total and specific fabs
Secondary Outcome Measures
Pharmacodynamic Effects of AZD9773 on TNF-alpha
TNF-alpha levels over approximately 6 days following the first dose
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01144624
Brief Title
A Study to Assess Safety,and Tolerability of 2 Doses of AZD9773 (CytoFab™) in Japanese With Severe Sepsis/Septic Shock
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2014
Overall Recruitment Status
Completed
Study Start Date
July 2010 (undefined)
Primary Completion Date
August 2011 (Actual)
Study Completion Date
August 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Severe Sepsis, Septic Shock
Keywords
TNF neutralisation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
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)
Arm Title
2
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
AZD9773
Other Intervention Name(s)
CytoFab™
Intervention Description
A single loading dose followed by 9 maintenance doses; doses to be given every 12 hours over a period of 5 days
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Intravenous infusion of a saline solution
Primary Outcome Measure Information:
Title
Safety and Tolerability of AZD9773
Description
Number of patients with treatment-emergent adverse events and number of patients who died over 28 days
Time Frame
28 day study period
Title
Pharmacokinetics of AZD9773
Description
Maximum concentration at steady state (Cmax ss) for serum total and specific fabs
Time Frame
From first dose to last dose (Day 5/6 or at premature treatment discontinuation)
Secondary Outcome Measure Information:
Title
Pharmacodynamic Effects of AZD9773 on TNF-alpha
Description
TNF-alpha levels over approximately 6 days following the first dose
Time Frame
Levels taken at baseline, over the dosing period (up to Day 5/6)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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:
Advanced human immunodeficiency virus (HIV) infection (CD4 ≤50/mm3).
Haemopoietic or lymphoreticular malignancies not in remission.
Receiving radiation therapy or chemotherapy.
Any organ or bone marrow transplant within the past 24 weeks.
Absolute neutrophil count <500 per μL.
High dose steroids or other immunocompromising drugs.
Concomitant diseases:
Deep-seated fungal infection or active tuberculosis.
Severe chronic liver disease associated with portal hypertension, cirrhosis, chronic ascites or Child-Pugh class C.
History of chronic hypercarbia, respiratory failure in past 6 months or use of home oxygen in the setting of severe chronic respiratory disease.
Neuromuscular disorders that impact breathing/spontaneous ventilation.
Quadriplegia.
Cardiac arrest in the past 30 days.
New York Heart Association functional Class III or IV due to heart failure or any disorder.
Burns over > 30% of body surface area in the past 5 days.
Medication and allergy disqualifications.
Treatment with anti-TNF agents within the last 8 weeks.
Previously received ovine derived products (CroFab™, DigiFab™).
Sheep product allergy or allergy to papain, chymopapain.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Justin Lindemann, MD
Organizational Affiliation
AstraZeneca
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Wayne Dankner, MD
Organizational Affiliation
PAREXEL International Medical Services
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Warren Botnick, MD
Organizational Affiliation
PAREXEL International Medical Services
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Sapporo-shi
State/Province
Hokkaido
Country
Japan
Facility Name
Research Site
City
Kobe
State/Province
Hyogo
Country
Japan
Facility Name
Research Site
City
Kumamoto-Shi
State/Province
Kumamoto
Country
Japan
Facility Name
Research Site
City
Sumiyoshi-ku
State/Province
Osaka
Country
Japan
Facility Name
Research Site
City
Hachioji
State/Province
Tokyo
Country
Japan
Facility Name
Research Site
City
Ohta-ku
State/Province
Tokyo
Country
Japan
Facility Name
Research Site
City
Osaka
Country
Japan
12. IPD Sharing Statement
Citations:
PubMed Identifier
23681364
Citation
Aikawa N, Takahashi T, Fujimi S, Yokoyama T, Yoshihara K, Ikeda T, Sadamitsu D, Momozawa M, Maruyama T. A Phase II study of polyclonal anti-TNF-alpha (AZD9773) in Japanese patients with severe sepsis and/or septic shock. J Infect Chemother. 2013 Oct;19(5):931-40. doi: 10.1007/s10156-013-0612-y. Epub 2013 May 17.
Results Reference
derived
Links:
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=241&filename=D0620C00005.pdf
Description
D0620C00005 Study Report Synopsis
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=241&filename=Japan_Ph2b_D0620C00005_redacted_text_18_July-2014.pdf
Description
redacted-CSP-D0620C00005.pdf
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A Study to Assess Safety,and Tolerability of 2 Doses of AZD9773 (CytoFab™) in Japanese With Severe Sepsis/Septic Shock
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