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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01144624
First received: June 7, 2010
Last updated: September 26, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Severe Sepsis
Septic Shock
Drug: AZD9773
Drug: Placebo
Phase 2

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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Safety and Tolerability of AZD9773 [ Time Frame: 28 day study period ] [ Designated as safety issue: Yes ]
    Number of patients with treatment-emergent adverse events and number of patients who died over 28 days

  • Pharmacokinetics of AZD9773 [ Time Frame: From first dose to last dose (Day 5/6 or at premature treatment discontinuation) ] [ Designated as safety issue: No ]
    Maximum concentration at steady state (Cmax ss) for serum total and specific fabs


Secondary Outcome Measures:
  • Pharmacodynamic Effects of AZD9773 on TNF-alpha [ Time Frame: Levels taken at baseline, over the dosing period (up to Day 5/6) ] [ Designated as safety issue: No ]
    TNF-alpha levels over approximately 6 days following the first dose


Enrollment: 20
Study Start Date: July 2010
Study Completion Date: August 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1

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)

Drug: AZD9773
A single loading dose followed by 9 maintenance doses; doses to be given every 12 hours over a period of 5 days
Other Name: CytoFab™
Placebo Comparator: 2 Drug: Placebo
Intravenous infusion of a saline solution

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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:

    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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01144624

Locations
Japan
Research Site
Sapporo-shi, Hokkaido, Japan
Research Site
Kobe, Hyogo, Japan
Research Site
Kumamoto-Shi, Kumamoto, Japan
Research Site
Sumiyoshi-ku, Osaka, Japan
Research Site
Hachioji, Tokyo, Japan
Research Site
Ohta-ku, Tokyo, Japan
Research Site
Osaka, Japan
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Justin Lindemann, MD AstraZeneca
Study Director: Wayne Dankner, MD PAREXEL International Medical Services
Study Director: Warren Botnick, MD PAREXEL International Medical Services
  More Information

Additional Information:
No publications provided by AstraZeneca

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01144624     History of Changes
Other Study ID Numbers: D0620C00005
Study First Received: June 7, 2010
Results First Received: December 11, 2012
Last Updated: September 26, 2014
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by AstraZeneca:
TNF neutralisation

Additional relevant MeSH terms:
Sepsis
Shock
Shock, Septic
Toxemia
Infection
Inflammation
Pathologic Processes
Systemic Inflammatory Response Syndrome

ClinicalTrials.gov processed this record on October 29, 2014