A Study to Compare the Efficacy and Safety of 2 Dosing Regimens of IV Infusions of AZD9773 (CytoFab™) With Placebo in Adult Patients With Severe Sepsis and/or Septic Shock

NCT01145560 | Completed Phase 2 Results

• 1 other identifier: D0620C00003
• Study Type: interventional
• Target: 300
• Locations: 7 countries
• Sites: 52

Brief Summary

The primary purpose of this study to evaluate the effect of two different doses of AZD9773 (CytoFab™) versus placebo on ventilator free days (VFDs) over the first 28 days after the start of dosing with AZD9773 in patients with severe sepsis and/or septic shock, who are already receiving appropriate standard of care treatment for sepsis.

Conditions

Severe Sepsis; Septic Shock

Keywords

severe sepsis; TNF neutralisation; septic shock patients

Outcome Measures

Primary Outcomes (1)

• Ventilator-free Days (VFDs) Over 28 Days

  Number of ventilator-free days (VFDs)

  Over 28 days following first dose

Secondary Outcomes (3)

• 7-day Mortality

  Over 7 days following first dose

• 28-day Mortality

  Over 28 days following first dose

• Safety and Tolerability

  All study visits (over 90 days following first dose)

Study Arms (3)

1

EXPERIMENTAL

AZD9773 250/50 units/kg

Drug: AZD9773

2

EXPERIMENTAL

AZD9773 500/100 units/kg

Drug: AZD9773

3

PLACEBO COMPARATOR

Drug: Placebo

Interventions

AZD9773 DRUG

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

Also known as: CytoFab™

1; 2

Placebo DRUG

Placebo

3

Eligibility Criteria

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

You may qualify if:

• 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).
• Stage III or IV cancer.
• Haemopoietic or lymphoreticular malignancies not in remission.
• Receiving radiation therapy or chemotherapy.
• Stem cell, organ or bone marrow transplant in the past 6 months.
• Absolute neutrophil count \<500 per μL.
• High dose steroids or other immunocompromising drugs.
• Concomitant diseases:
• Deep seated fungal infection or active tuberculosis.
• Cirrhosis with portal hypertension or Childs-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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (52)

Research Site

Blacktown, New South Wales, Australia

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Wollongong, New South Wales, Australia

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Herston, Queensland, Australia

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Nambour, Queensland, Australia

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Woollongabba, Queensland, Australia

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Adelaide, South Australia, Australia

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Clayton, Victoria, Australia

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Footscray, Victoria, Australia

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Fremantle, Western Australia, Australia

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Antwerp, Belgium, Belgium

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Brussels, Belgium, Belgium

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Genk, Belgium, Belgium

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Godinne, Belgium, Belgium

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Liège, Belgium, Belgium

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Ottignies, Belgium, Belgium

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Edmonton, Alberta, Canada

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Vancouver, British Columbia, Canada

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Victoria, British Columbia, Canada

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Winnipeg, Manitoba, Canada

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Halifax, Nova Scotia, Canada

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Ottawa, Ontario, Canada

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Windsor, Ontario, Canada

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Québec, Quebec, Canada

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Hradec Králové, Czechia

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Prague, Czechia

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Ústí nad Labem, Czechia

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Kuopio, Finland

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Tampere, Finland

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Angers, France

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Dijon, France

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La Roche-sur-Yon, France

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Limoges, France

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Montauban, France

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Nantes, France

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Nîmes, France

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Orléans, France

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Paris, France

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Poitiers, France

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Saint-Michel, France

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Toulon, France

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Toulouse, France

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Tours, France

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Vandœuvre-lès-Nancy, France

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Palma de Mallorca, Balearic Islands, Spain

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Sabadell, Barcelona, Spain

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Barcelona, Catalonia, Spain

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Terrassa, Catalonia, Spain

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Santiago de Compostela, Coruna, Spain

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Getafe, Madrid, Spain

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Madrid, Madrid, Spain

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Oviedo, Principality of Asturias, Spain

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Valencia, Valencia, Spain

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Related Publications (1)

• Yates JW, Das S, Mainwaring G, Kemp J. Population pharmacokinetic/pharmacodynamic modelling of the anti-TNF-alpha polyclonal fragment antibody AZD9773 in patients with severe sepsis. J Pharmacokinet Pharmacodyn. 2012 Dec;39(6):591-9. doi: 10.1007/s10928-012-9270-4. Epub 2012 Sep 23.

  PMID: 23001587 DERIVED

Related Links

• CSR-D0620C00003.pdf
• redacted-CSP-D0620C00003.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

• Gordon Bernard, MD

  Vanderbilt University

  PRINCIPAL INVESTIGATOR

• Warren Botnick, MD

  Parexel

  STUDY DIRECTOR

• Justin Lindemann, MD

  AstraZeneca

  STUDY DIRECTOR

• Wayne Dankner, MD

  Parexel

  STUDY DIRECTOR

• Jiri Juchelka, MD

  Parexel

  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: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2010
• First Posted: June 16, 2010
• Study Start: October 1, 2010
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2012
• Last Updated: October 6, 2014
• Results First Posted: September 23, 2013

Record last verified: 2014-09

Locations

AU (9); CA (8); CZ (3); FI (2); FR (15); BE (6); ES (9)