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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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ClinicalTrials.gov Identifier: NCT01144624
Recruitment Status : Completed
First Posted : June 15, 2010
Results First Posted : August 22, 2013
Last Update Posted : October 6, 2014
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE June 7, 2010
First Posted Date  ICMJE June 15, 2010
Results First Submitted Date  ICMJE December 11, 2012
Results First Posted Date  ICMJE August 22, 2013
Last Update Posted Date October 6, 2014
Study Start Date  ICMJE July 2010
Actual Primary Completion Date August 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 19, 2013)
  • Safety and Tolerability of AZD9773 [ Time Frame: 28 day study period ]
    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) ]
    Maximum concentration at steady state (Cmax ss) for serum total and specific fabs
Original Primary Outcome Measures  ICMJE
 (submitted: June 14, 2010)
  • Assess the safety and tolerability of two different doses of AZD9773 by means of frequency of adverse events, mortality, ECGs, vital signs, laboratory tests and other safety evaluations, [ Time Frame: Over 28 days following first dose ]
  • Assess the pharmacokinetics of AZD9773 in Japanese patients with severe sepsis and/or septic shock by means of measuring concentrations of AZD9773 in serum and urine [ Time Frame: Pharmacokinetics of first dose, two interim doses and last dose (Over approximately 6 days following the first dose) ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 19, 2013)
Pharmacodynamic Effects of AZD9773 on TNF-alpha [ Time Frame: Levels taken at baseline, over the dosing period (up to Day 5/6) ]
TNF-alpha levels over approximately 6 days following the first dose
Original Secondary Outcome Measures  ICMJE
 (submitted: June 14, 2010)
Make a preliminary assessment of the pharmacodynamics in terms of the effect on TNFα, IL-6 and IL 8. [ Time Frame: Pharmacodynamics of first dose to last dose (Over approximately 6 days following the first dose) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Assess Safety,and Tolerability of 2 Doses of AZD9773 (CytoFab™) in Japanese With Severe Sepsis/Septic Shock
Official Title  ICMJE 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
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Severe Sepsis
  • Septic Shock
Intervention  ICMJE
  • 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™
  • Drug: Placebo
    Intravenous infusion of a saline solution
Study Arms  ICMJE
  • 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)

    Intervention: Drug: AZD9773
  • Placebo Comparator: 2
    Intervention: Drug: Placebo
Publications * 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-α (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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 14, 2010)
20
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE August 2011
Actual Primary Completion Date August 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Japan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01144624
Other Study ID Numbers  ICMJE D0620C00005
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Justin Lindemann, MD AstraZeneca
Study Director: Wayne Dankner, MD PAREXEL International Medical Services
Study Director: Warren Botnick, MD PAREXEL International Medical Services
PRS Account AstraZeneca
Verification Date September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP