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

NCT01144624 | Completed Phase 2 Results DMC

• 1 other identifier: D0620C00005
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 7

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.

Conditions

Severe Sepsis; Septic Shock

Keywords

TNF neutralisation

Outcome Measures

Primary Outcomes (2)

• 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

• 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)

Secondary Outcomes (1)

• Pharmacodynamic Effects of AZD9773 on TNF-alpha

  Levels taken at baseline, over the dosing period (up to Day 5/6)

Study Arms (2)

1

EXPERIMENTAL

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

2

PLACEBO COMPARATOR

Drug: Placebo

Interventions

AZD9773 DRUG

A single loading dose followed by 9 maintenance doses; doses to be given every 12 hours over a period of 5 days

Also known as: CytoFab™

1

Placebo DRUG

Intravenous infusion of a saline solution

2

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (7)

Research Site

Sapporo, Hokkaido, Japan

Location

Research Site

Kobe, Hyōgo, Japan

Location

Research Site

Kumamoto, Kumamoto, Japan

Location

Research Site

Osaka, Osaka, Japan

Location

Research Site

Sumiyoshi-ku, Osaka, Japan

Location

Research Site

Hachiōji, Tokyo, Japan

Location

Research Site

Ohta-ku, Tokyo, Japan

Location

Related Publications (1)

• 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.

  PMID: 23681364 DERIVED

Related Links

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

MeSH Terms

Conditions

Sepsis; Shock, Septic

Interventions

AZD9773; CytoFab

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Results Point of Contact

• Title: Justin Lindemann
• Organization: AstraZeneca

ClinicalTrialTransparency@astrazeneca.com

Study Officials

• Justin Lindemann, MD

  AstraZeneca

  STUDY DIRECTOR

• Wayne Dankner, MD

  PAREXEL International Medical Services

  STUDY DIRECTOR

• Warren Botnick, MD

  PAREXEL International Medical Services

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2010
• First Posted: June 15, 2010
• Study Start: July 1, 2010
• Primary Completion: August 1, 2011
• Study Completion: August 1, 2011
• Last Updated: October 6, 2014
• Results First Posted: August 22, 2013

Record last verified: 2014-09

Locations

JP (7)