Severe SepsisPhase 2NCT01144624

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

A Phase 2 study testing AZD9773 in people with Severe Sepsis and Septic Shock, run by AstraZeneca at 7 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial 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. Read more about this study

Who is it for?: Ages 20 years and older
Conditions the study is for: Severe Sepsis, Septic Shock
What is being tested?: AZD9773
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 20 participants
Where: 7 sitesJapan
Study dates: Jul 2010to Aug 2011
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 20 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Show all 20Show fewer

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.
Burns over > 30% of body surface area in the past 5 days.
Medication and allergy disqualifications.
Treatment with anti-TNF agents within the last 8 weeks.
Previously received ovine derived products (CroFab™, DigiFab™).
Sheep product allergy or allergy to papain, chymopapain.

Trial locations and contacts

7 sites in 1 country.

City, postcode or hospital

7 sites in 1 country

Japan7 sites

Research Site
Hachiōji, Tokyo
Research Site
Kobe, Hyōgo
Research Site
Kumamoto, Kumamoto
Research Site
Ohta-ku, Tokyo
Research Site
Osaka, Osaka
Research Site
Sapporo, Hokkaido
Research Site
Sumiyoshi-ku, Osaka

Other trials in Japan

About this study

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

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
Being tested: AZD9773, Placebo
Keywords: TNF neutralisation
Medical subject headings: Sepsis, Shock, Septic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AZD9773Drug
Also called CytoFab™
A single loading dose followed by 9 maintenance doses; doses to be given every 12 hours over a period of 5 days
PlaceboDrug
Intravenous infusion of a saline solution

Study groups in NCT01144624
Study group	Role	What they receive
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) Receives: Drug: AZD9773
2	Placebo comparator	Not described Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Safety and Tolerability of AZD9773
Number of patients with treatment-emergent adverse events and number of patients who died over 28 days
Measured: 28 day study period
Pharmacokinetics of AZD9773
Maximum concentration at steady state (Cmax ss) for serum total and specific fabs
Measured: From first dose to last dose (Day 5/6 or at premature treatment discontinuation)

Secondary outcomes (1)

Pharmacodynamic Effects of AZD9773 on TNF-alpha
TNF-alpha levels over approximately 6 days following the first dose
Measured: Levels taken at baseline, over the dosing period (up to Day 5/6)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 2010Aug 2011

First posted15 Jun 2010 (estimated)
Study startJul 2010
Primary completionAug 2011
Study completionAug 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Severe SepsisStudies of the same condition, open and under way.
More trials run by AstraZenecaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 20 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01144624
Sponsor's protocol ID: D0620C00005
Status last verified: Sep 2014
First submitted: 7 Jun 2010
Last updated: 6 Oct 2014
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

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-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.
PubMed 23681364

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 6 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01144624
Acronym / sponsor ID: D0620C00005
Conditions: Severe Sepsis, Septic Shock
Keywords: TNF neutralisation
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 20 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Study start: Jul 2010
Primary completion: Aug 2011 (actual)
Study completion: Aug 2011 (actual)
First posted: 15 Jun 2010 (estimated)
Results: Posted 22 Aug 2013

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
1	Experimental	Drug: AZD9773AZD9773 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)
2	Placebo comparator	Drug: Placebo

Who may qualify

Ages: 20 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

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.

Key exclusion criteria (20 listed)

Immunocompromising comorbidities or concomitant medications:
Concomitant diseases:
Medication and allergy disqualifications.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
AZD9773Also: CytoFab™A single loading dose followed by 9 maintenance doses; doses to be given every 12 hours over a period of 5 days	Drug	1
PlaceboIntravenous infusion of a saline solution	Drug	2

Primary outcome

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

1 secondary outcome

Pharmacodynamic Effects of AZD9773 on TNF-alpha
Time frame: Levels taken at baseline, over the dosing period (up to Day 5/6)

Results and safety

Results posted to the registry on 22 Aug 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Dose Cohort 1	7	7
Dose Cohort 2	7	7
Placebo	6	6

Primary outcome: Safety and Tolerability of AZD9773

Time frame: 28 day study period. Number. Unit: Participants

Measure	Arm 1 - Dose Cohort 1 n = 7	Arm 2 - Dose Cohort 2 n = 7	Arm 3 - Placebo n = 6
Number of Patients with Treatment-Emergent AEs	7	7	6
Number of Patients who Died over 28 days	1	0	2

Population analysed: Safety analysis set

Primary outcome: Pharmacokinetics of AZD9773

Time frame: From first dose to last dose (Day 5/6 or at premature treatment discontinuation). Geometric mean (Full Range). Unit: ug/mL

Measure	Arm 1 - Dose Cohort 1 n = 7	Arm 2 - Dose Cohort 2 n = 5	Arm 3 - Placebo n = 0
Cmax ss for serum total fabs	38.48 (30.5 to 62.4)	71.04 (41.7 to 90.7)	–
Cmax ss for serum specific fabs	1.823 (1.31 to 2.62)	3.335 (1.92 to 4.62)	–

Population analysed: Pharmacokinetic analysis set

1 secondary outcome is reported in the full results.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Dose Cohort 1	4 of 7 (57.1%)	7 of 7 (100%)	Not reported
Dose Cohort 2	1 of 7 (14.3%)	7 of 7 (100%)	Not reported
Placebo	1 of 6 (16.7%)	6 of 6 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 23681364Aikawa 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.
D0620C00005 Study Report SynopsisLink provided by the sponsor.
redacted-CSP-D0620C00005.pdfLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Justin Lindemann, MD study director

AstraZeneca

Wayne Dankner, MD study director

PAREXEL International Medical Services

Warren Botnick, MD study director

PAREXEL International Medical Services

7 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing AZD9773 in people with Severe Sepsis and Septic Shock, run by AstraZeneca at 7 sites in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Oct 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Aug 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety and Tolerability of AZD9773 (time frame: 28 day study period). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01144624, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2014.