Clinical trial NCT01144624: A Study to Assess Safety,and Tolerability of 2 Doses of AZD9773 (CytoFab™) in Japanese With Severe Sepsis/Septic Shock
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Severe Sepsis
Septic Shock
Keywords: TNF neutralisation
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2010-06-15
Enrollment: 20
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Safety and Tolerability of AZD9773
timeFrame: 28 day study period
measure: Pharmacokinetics of AZD9773
timeFrame: From first dose to last dose (Day 5/6 or at premature treatment discontinuation)
Secondary outcomes:
measure: Pharmacodynamic Effects of AZD9773 on TNF-alpha
timeFrame: Levels taken at baseline, over the dosing period (up to Day 5/6)
Other outcomes:
Locations:
city: Sapporo-shi
country: Japan
facility: Research Site
state: Hokkaido
city: Kobe
country: Japan
facility: Research Site
state: Hyogo
city: Kumamoto-Shi
country: Japan
facility: Research Site
state: Kumamoto
city: Sumiyoshi-ku
country: Japan
facility: Research Site
state: Osaka
city: Hachioji
country: Japan
facility: Research Site
state: Tokyo
city: Ohta-ku
country: Japan
facility: Research Site
state: Tokyo
city: Osaka
country: Japan
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: Justin Lindemann, MD
role: STUDY_DIRECTOR
affiliation: PAREXEL International Medical Services
name: Wayne Dankner, MD
role: STUDY_DIRECTOR
affiliation: PAREXEL International Medical Services
name: Warren Botnick, MD
role: STUDY_DIRECTOR
References:
citation: 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.