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

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:

MedlinePlus related topics: Sepsis Shock

U.S. FDA Resources

Further study details as provided by AstraZeneca:

Primary Outcome Measures:

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 ] [ Designated as safety issue: Yes ]
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) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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) ] [ Designated as safety issue: No ]

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

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

No publications provided

Responsible Party:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT01144624 History of Changes
Other Study ID Numbers:	D0620C00005
Study First Received:	June 7, 2010
Last Updated:	June 13, 2012
Health Authority:	Japan: Ministry of Health, Labor and Welfare

Keywords provided by AstraZeneca:

TNF neutralisation

Additional relevant MeSH terms:

Sepsis
Toxemia
Shock
Shock, Septic

Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes

ClinicalTrials.gov processed this record on June 17, 2013