Severe SepsisPhase 2NCT00615017

AZD9773 Dose Escalation Study

A Phase 2 study testing AZD9773 (CytoFab) in people with Severe Sepsis, run by AstraZeneca at 26 sites in United States.

Completed

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

Official record

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Trial summary

This is a double-blind, placebo-controlled, multi-center, dose-escalation study to assess the safety, tolerability, Pharmacokinetics and Pharmacodynamics of single and multiple ascending intravenous infusions of CytoFab (AZD9773) in adult patients with severe sepsis. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Severe Sepsis
What is being tested?: AZD9773 (CytoFab)
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 70 participants
Where: 26 sitesUnited States
Study dates: Jan 2008to Jul 2009
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 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Clinical evidence of infection requiring treatment with parenteral antibiotics
Patients must meet multiple Systemic Inflammatory Response Syndrome (SIRS) criteria
Patients must meet criteria for cardiovascular and/or respiratory dysfunction
Sepsis (infection plus SIRS criteria) must be present prior to organ dysfunction

Who cannot join

Moribund and death is considered imminent, or patient not expected to survive 90 days because of underlying medical condition, or classified as Do Not Resuscitate or Do Not Treat
Patient cannot attain a MAP >60 mmHg when measured via an arterial line and/or a Systolic Blood Pressure (SBP) >80 mmHg in the presence of vasopressors and iv fluids for a period of ≥2 hours
Receiving immunosuppressants, or high dose steroids within 2 months of provision of informed consent
Any history of hypersensitivity reaction to sheep products, latex, papain or papaya, or chymopapain or previously administered antivenom manufactured using ovine serum, digoxin immune fab (DigiFab™ , DIGIBIND® ), crotalidae polyvalent immune fab (ovine) (CroFab™ ), or other sheep derived product.
Treatment with anti Tumor-Necrosis-Factor (anti-TNF) antibodies within 8 weeks before provision of written informed consent.

Trial locations and contacts

26 sites in 1 country.

City, postcode or hospital

26 sites in 1 country

United States26 sites

Research Site
Baltimore, Maryland
Research Site
Bay Pines, Florida
Research Site
Birmingham, Alabama
Research Site
Brooklyn, New York
Research Site
Camden, New Jersey
Research Site
Chicago, Illinois
Research Site
Columbus, Ohio
Research Site
Durham, North Carolina
Research Site
Galveston, Texas
Research Site
Greensboro, North Carolina
Research Site
Hazard, Kentucky
Research Site
Houston, Texas
Research Site
Indianapolis, Indiana
Research Site
Iowa City, Iowa
Research Site
Kansas City, Missouri
Research Site
Lexington, Kentucky
Research Site
Miami, Florida
Research Site
Nashville, Tennessee
Research Site
New York, New York
Research Site
Newark, Delaware
Research Site
Newark, New Jersey
Research Site
Oak Park, Illinois
Research Site
Oklahoma City, Oklahoma
Research Site
Peoria, Illinois
Research Site
Rochester, New York
Research Site
Winston-Salem, North Carolina

Other trials in United States

About this study

Official title: A Placebo-controlled, Double-blind, Dose-escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics and Pharmacodynamics of Single and Multiple Intravenous Infusions of CytoFab (AZD9773) in Patients With Severe Sepsis

Conditions: Severe Sepsis
Being tested: AZD9773 (CytoFab), Placebo
Keywords: Sepsis, septic shock, Systemic Inflammatory Response Syndrome
Medical subject headings: Sepsis, Shock, Septic, Systemic Inflammatory Response Syndrome

What participants receive

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

AZD9773 (CytoFab)Drug
intravenous infusions
PlaceboOther
Placebo

Study groups in NCT00615017
Study group	Role	What they receive
AZD9773 cohort 1 (50 units/kg)	Experimental	AZD9773: single infusion of 50 units/kg Receives: Drug: AZD9773 (CytoFab)
AZD9773 cohort 2 (250 units/kg)	Experimental	AZD9773: single infusion of 250 units/kg Receives: Drug: AZD9773 (CytoFab)
AZD9773 cohort 3 (250/50 units/kg)	Experimental	AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs Receives: Drug: AZD9773 (CytoFab)
AZD9773 cohort 4 (500/100 units/kg)	Experimental	AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs Receives: Drug: AZD9773 (CytoFab)
AZD9773 cohort 5 (750/250 units/kg)	Experimental	AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs Receives: Drug: AZD9773 (CytoFab)
Placebo	Placebo comparator	Placebo Receives: Other: Placebo

What is being measured

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

Change From Baseline in Creatinine Values
Change in creatinine values from baseline (pre-infusion) to follow-up (28 days after the start of study drug administration) [calculated as Day 28 mean minus baseline mean]. Safety analysis set (ie all patients who started study drug infusion).
Measured: End of study (Day 28)
Change From Baseline in Alanine Aminotransferase Values
Change in alanine aminotransferase values from baseline (pre-infusion) to follow-up (28 days after the start of study drug administration) [calculated as Day 28 mean minus baseline mean]. Safety analysis set (ie all patients who started study drug infusion).
Measured: End of study (Day 28)
Change From Baseline in Aspartate Aminotransferase Values
Change in aspartate aminotransferase values from baseline (pre-infusion) to follow-up (28 days after the start of study drug administration) [calculated as Day 28 mean minus baseline mean]. Safety analysis set (ie all patients who started study drug infusion).
Measured: End of study (Day 28)
Change From Baseline in Bilirubin Values
Change in bilirubin values from baseline (pre-infusion) to follow-up (28 days after the start of study drug administration) [calculated as Day 28 mean minus baseline mean]. Safety analysis set (ie all patients who started study drug infusion).
Measured: End of study (Day 28)
Change From Baseline in Haemoglobin Values
Change in haemoglobin values from baseline (pre-infusion) to follow-up (28 days after the start of study drug administration) [calculated as Day 28 mean minus baseline mean]. Safety analysis set (ie all patients who started study drug infusion).
Measured: End of study (Day 28)
Change From Baseline in White Blood Cell Values
Change in white blood cell values from baseline (pre-infusion) to follow-up (28 days after the start of study drug administration) [calculated as Day 28 mean minus baseline mean]. Safety analysis set (ie all patients who started study drug infusion).
Measured: End of study (Day 28)
Change From Baseline in Platelet Count Values
Change in platelet count values from baseline (pre-infusion) to follow-up (28 days after the start of study drug administration) [calculated as Day 28 mean minus baseline mean]. Safety analysis set (ie all patients who started study drug infusion).
Measured: End of study (Day 28)
Change From Baseline in Prothrombin Time Values
Change in prothrombin time values from baseline (pre-infusion) to Day 7 [calculated as Day 7 mean minus baseline mean]. Safety analysis set (ie all patients who started study drug infusion).
Measured: Day 7
Change From Baseline in Troponin I
Change in troponin I values from baseline (pre-infusion) to Day 6 [calculated as Day 6 mean minus baseline mean]. Safety analysis set (ie all patients who started study drug infusion).
Measured: Day 6
Change From Baseline in QT With Fridericia Correction (QTcF), Where QT is Measured by ECG, and is the Time Interval Between the Start of the Q Wave and the End of the T Wave in the Heart's Electrical Cycle.
Change in QTcF from baseline (pre-infusion) to Day 1 (end of infusion) for Cohorts 1 and 2 [calculated as Day 1 mean minus baseline mean] and Day 5 (end of infusion) for Cohorts 3 to 5 and placebo [calculated as Day 5 mean minus baseline mean]. Safety analysis set (ie all patients who started study drug infusion).
Measured: Day 1 (end of infusion) for Cohorts 1 and 2; Day 5 (end of infusion) for Cohorts 3 to 5 and placebo
Change From Baseline in Calculated Mean Arterial Blood Pressure
Change in calculated mean arterial pressure from baseline (pre-infusion) to Day 14 [calculated as Day 14 mean minus baseline mean]. Safety analysis set (ie all patients who started study drug infusion).
Measured: Day 14
Change From Baseline in Body Weight
Change in body weight from baseline (pre-infusion) to Day 6 [calculated as Day 6 mean minus baseline mean]. Safety analysis set (ie all patients who started study drug infusion).
Measured: Day 6

Secondary outcomes (12)

28-Day Mortality
The number of patients who had died at Day 28. Safety analysis set (ie all patients who started study drug infusion).
Measured: End of study (Day 28)
Change From Baseline in Sequential Organ Failure Assessment (SOFA) Scores
Change in SOFA (Sequential Organ Failure Assessment) scores from baseline (pre-infusion) to Day 6 [calculated as Day 6 mean minus baseline mean]. The SOFA score is out of a maximum of 24 (units on a scale 0 to 24). The higher the score, the worse the organ system functioning. Safety analysis set (ie all patients who started study drug infusion).
Measured: Day 6
Area Under the Serum Concentration-time Curve From 0 to 12 Hours (AUC(0-12)) of Single Dose AZD9773 Serum Total Fabs (Cohorts 1 and 2)
AUC(0-12) for single dose AZD9773 serum total Fabs (cohorts 1 and 2). PK analysis set (ie a subset of the safety analysis set including only those patients without important deviations that could affect the PK).
Measured: Day 1 [PK samples taken pre-dose, the end of each infusion rate and then at 0.5, 1, 2, 8, and 12h post-(last) infusion]
Terminal Half-life (t1/2) of Single Dose AZD9773 Serum Total Fabs (Cohorts 1 and 2)
t1/2 of single dose AZD9773 serum total Fabs (cohorts 1 and 2). PK analysis set (ie a subset of the safety analysis set including only those patients without important deviations that could affect the PK).
Measured: Day 1 [PK samples taken pre-dose, the end of each infusion rate and then at 0.5, 1, 2, 8, 12, 24, 48, and 72 h post-(last) infusion]
Total Apparent Clearance (CL) of Single Dose AZD9773 Serum Total Fabs (Cohorts 1 and 2)
CL of single dose AZD9773 serum total Fabs (cohorts 1 and 2). PK analysis set (ie a subset of the safety analysis set including only those patients without important deviations that could affect the PK).
Measured: Day 1 [PK samples taken pre-dose, the end of each infusion rate and then at 0.5, 1, 2, 8, 12, 24, 48, and 72 h post-(last) infusion]
AUC(0-12) of Loading Dose AZD9773 Serum Total Fabs (Cohorts 3, 4 and 5)
AUC(0-12) of loading dose AZD9773 serum total Fabs (cohorts 3, 4 and 5). PK analysis set (ie a subset of the safety analysis set including only those patients without important deviations that could affect the PK).
Measured: Day 1 [PK samples taken pre-dose, the end of each infusion rate and then at 0.5, 1, 2, 8 and 12 h post-(last) infusion]
Maximum (End of Infusion) Serum Concentration (Cinf) of Loading Dose AZD9773 Serum Total Fabs (Cohorts 3,4 and 5)
Cinf of loading dose AZD9773 serum total Fabs (cohorts 3, 4 and 5). PK analysis set (ie a subset of the safety analysis set including only those patients without important deviations that could affect the PK).
Measured: Day 1 [PK samples taken pre-dose, the end of each infusion rate and then at 0.5, 1, 2, 8 and 12 h post-(last)infusion]
Time to Reach Cinf (Tmax) of Loading Dose AZD9773 Serum Total Fabs (Cohorts 3, 4 and 5)
tmax of loading dose AZD9773 serum total Fabs (cohorts 3, 4 and 5). PK analysis set (ie a subset of the safety analysis set including only those patients without important deviations that could affect the PK).
Measured: Day 1 [PK samples taken pre-dose, the end of each infusion rate and then at 0.5, 1, 2, 8 and 12 h post-(last)infusion]
AUC(0-12) of Maintenance Dose AZD9773 Serum Total Fabs (Cohorts 3, 4 and 5)
AUC(0-12) of maintenance dose AZD9773 serum total Fabs (cohorts 3, 4 and 5). PK analysis set (ie a subset of the safety analysis set including only those patients without important deviations that could affect the PK).
Measured: PK samples taken pre-dose of Doses 5,7 and 9, then at 0, 0.5, 1, 2, 8 and 12 h post dose 9 infusion
Cinf of Maintenance Dose AZD9773 Serum Total Fabs (Cohorts 3, 4 and 5)
Cinf of maintenance dose AZD9773 serum total Fabs (cohorts 3, 4 and 5). PK analysis set (ie a subset of the safety analysis set including only those patients without important deviations that could affect the PK).
Measured: PK samples taken pre-dose of Doses 5,7 and 9, then at 0, 0.5, 1, 2, 8 and 12 h post dose 9 infusion
Tmax of Maintenance Dose AZD9773 Serum Total Fabs (Cohorts 3, 4 and 5)
tmax of maintenance dose AZD9773 serum total Fabs (cohorts 3, 4 and 5). PK analysis set (ie a subset of the safety analysis set including only those patients without important deviations that could affect the PK).
Measured: PK samples taken pre-dose of Doses 5,7 and 9, then at 0, 0.5, 1, 2, 8 and 12 h post dose 9 infusion
Number of Patients Below Tumour Necrosis Factor (TNF)-Alpha Limit of Quantification (LOQ) at 24 Hours (n< LOQ)
Number of patients below tumour necrosis factor (TNF)-alpha limit of quantification (LOQ) at 24 hours (n< LOQ) measured by ELISA (LOQ = 1.3 pg/mL). Safety analysis set (ie all patients who started study drug infusion).
Measured: 24 hours

Timeline

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

Jan 2008Jul 2009

First posted14 Feb 2008 (estimated)
Study startJan 2008
Primary completionJul 2009
Study completionJul 2009

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: Single group
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 70 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00615017
Sponsor's protocol ID: D0620C00004
Status last verified: Jul 2013
First submitted: 31 Jan 2008
Last updated: 22 Aug 2013
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

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.
PubMed 23001587

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?

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Study at a glance

From the registry record, last updated by the sponsor on 22 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Placebo-controlled, Double-blind, Dose-escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics and Pharmacodynamics of Single and Multiple Intravenous Infusions of CytoFab (AZD9773) in Patients With Severe Sepsis
ClinicalTrials.gov ID: NCT00615017
Acronym / sponsor ID: D0620C00004
Conditions: Severe Sepsis
Keywords: Sepsis, septic shock, Systemic Inflammatory Response Syndrome
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 70 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Study start: Jan 2008
Primary completion: Jul 2009 (actual)
Study completion: Jul 2009 (actual)
First posted: 14 Feb 2008 (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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Single group
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 6

Arm	Type	Receives
AZD9773 cohort 1 (50 units/kg)	Experimental	Drug: AZD9773 (CytoFab)AZD9773: single infusion of 50 units/kg
AZD9773 cohort 2 (250 units/kg)	Experimental	Drug: AZD9773 (CytoFab)AZD9773: single infusion of 250 units/kg
AZD9773 cohort 3 (250/50 units/kg)	Experimental	Drug: AZD9773 (CytoFab)AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs
AZD9773 cohort 4 (500/100 units/kg)	Experimental	Drug: AZD9773 (CytoFab)AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs
AZD9773 cohort 5 (750/250 units/kg)	Experimental	Drug: AZD9773 (CytoFab)AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs
Placebo	Placebo comparator	Other: PlaceboPlacebo

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

Clinical evidence of infection requiring treatment with parenteral antibiotics
Patients must meet multiple Systemic Inflammatory Response Syndrome (SIRS) criteria
Patients must meet criteria for cardiovascular and/or respiratory dysfunction
Sepsis (infection plus SIRS criteria) must be present prior to organ dysfunction

Key exclusion criteria (5 listed)

Moribund and death is considered imminent, or patient not expected to survive 90 days because of underlying medical condition, or classified as Do Not Resuscitate or Do Not Treat
Patient cannot attain a MAP >60 mmHg when measured via an arterial line and/or a Systolic Blood Pressure (SBP) >80 mmHg in the presence of vasopressors and iv fluids for a period of ≥2 hours
Receiving immunosuppressants, or high dose steroids within 2 months of provision of informed consent
Any history of hypersensitivity reaction to sheep products, latex, papain or papaya, or chymopapain or previously administered antivenom manufactured using ovine serum, digoxin immune fab (DigiFab™ , DIGIBIND® ), crotalidae polyvalent immune fab (ovine) (CroFab™ ), or other sheep derived product.
Treatment with anti Tumor-Necrosis-Factor (anti-TNF) antibodies within 8 weeks before provision of written informed consent.

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
AZD9773 (CytoFab)intravenous infusions	Drug	AZD9773 cohort 1 (50 units/kg), AZD9773 cohort 2 (250 units/kg), AZD9773 cohort 3 (250/50 units/kg), AZD9773 cohort 4 (500/100 units/kg), AZD9773 cohort 5 (750/250 units/kg)
PlaceboPlacebo	Other	Placebo

Primary outcome

Change From Baseline in Creatinine Values
Time frame: End of study (Day 28)
Change in creatinine values from baseline (pre-infusion) to follow-up (28 days after the start of study drug administration) [calculated as Day 28 mean minus baseline mean]. Safety analysis set (ie all patients who started study drug infusion).
Change From Baseline in Alanine Aminotransferase Values
Time frame: End of study (Day 28)
Change in alanine aminotransferase values from baseline (pre-infusion) to follow-up (28 days after the start of study drug administration) [calculated as Day 28 mean minus baseline mean]. Safety analysis set (ie all patients who started study drug infusion).
Change From Baseline in Aspartate Aminotransferase Values
Time frame: End of study (Day 28)
Change in aspartate aminotransferase values from baseline (pre-infusion) to follow-up (28 days after the start of study drug administration) [calculated as Day 28 mean minus baseline mean]. Safety analysis set (ie all patients who started study drug infusion).
Change From Baseline in Bilirubin Values
Time frame: End of study (Day 28)
Change in bilirubin values from baseline (pre-infusion) to follow-up (28 days after the start of study drug administration) [calculated as Day 28 mean minus baseline mean]. Safety analysis set (ie all patients who started study drug infusion).
Change From Baseline in Haemoglobin Values
Time frame: End of study (Day 28)
Change in haemoglobin values from baseline (pre-infusion) to follow-up (28 days after the start of study drug administration) [calculated as Day 28 mean minus baseline mean]. Safety analysis set (ie all patients who started study drug infusion).
Change From Baseline in White Blood Cell Values
Time frame: End of study (Day 28)
Change in white blood cell values from baseline (pre-infusion) to follow-up (28 days after the start of study drug administration) [calculated as Day 28 mean minus baseline mean]. Safety analysis set (ie all patients who started study drug infusion).
Change From Baseline in Platelet Count Values
Time frame: End of study (Day 28)
Change in platelet count values from baseline (pre-infusion) to follow-up (28 days after the start of study drug administration) [calculated as Day 28 mean minus baseline mean]. Safety analysis set (ie all patients who started study drug infusion).
Change From Baseline in Prothrombin Time Values
Time frame: Day 7
Change in prothrombin time values from baseline (pre-infusion) to Day 7 [calculated as Day 7 mean minus baseline mean]. Safety analysis set (ie all patients who started study drug infusion).
Change From Baseline in Troponin I
Time frame: Day 6
Change in troponin I values from baseline (pre-infusion) to Day 6 [calculated as Day 6 mean minus baseline mean]. Safety analysis set (ie all patients who started study drug infusion).
Change From Baseline in QT With Fridericia Correction (QTcF), Where QT is Measured by ECG, and is the Time Interval Between the Start of the Q Wave and the End of the T Wave in the Heart's Electrical Cycle.
Time frame: Day 1 (end of infusion) for Cohorts 1 and 2; Day 5 (end of infusion) for Cohorts 3 to 5 and placebo
Change in QTcF from baseline (pre-infusion) to Day 1 (end of infusion) for Cohorts 1 and 2 [calculated as Day 1 mean minus baseline mean] and Day 5 (end of infusion) for Cohorts 3 to 5 and placebo [calculated as Day 5 mean minus baseline mean]. Safety analysis set (ie all patients who started study drug infusion).
Change From Baseline in Calculated Mean Arterial Blood Pressure
Time frame: Day 14
Change in calculated mean arterial pressure from baseline (pre-infusion) to Day 14 [calculated as Day 14 mean minus baseline mean]. Safety analysis set (ie all patients who started study drug infusion).
Change From Baseline in Body Weight
Time frame: Day 6
Change in body weight from baseline (pre-infusion) to Day 6 [calculated as Day 6 mean minus baseline mean]. Safety analysis set (ie all patients who started study drug infusion).

12 secondary outcomes

28-Day Mortality
Time frame: End of study (Day 28)
Change From Baseline in Sequential Organ Failure Assessment (SOFA) Scores
Time frame: Day 6
Area Under the Serum Concentration-time Curve From 0 to 12 Hours (AUC(0-12)) of Single Dose AZD9773 Serum Total Fabs (Cohorts 1 and 2)
Time frame: Day 1 [PK samples taken pre-dose, the end of each infusion rate and then at 0.5, 1, 2, 8, and 12h post-(last) infusion]
Terminal Half-life (t1/2) of Single Dose AZD9773 Serum Total Fabs (Cohorts 1 and 2)
Time frame: Day 1 [PK samples taken pre-dose, the end of each infusion rate and then at 0.5, 1, 2, 8, 12, 24, 48, and 72 h post-(last) infusion]
Total Apparent Clearance (CL) of Single Dose AZD9773 Serum Total Fabs (Cohorts 1 and 2)
Time frame: Day 1 [PK samples taken pre-dose, the end of each infusion rate and then at 0.5, 1, 2, 8, 12, 24, 48, and 72 h post-(last) infusion]
AUC(0-12) of Loading Dose AZD9773 Serum Total Fabs (Cohorts 3, 4 and 5)
Time frame: Day 1 [PK samples taken pre-dose, the end of each infusion rate and then at 0.5, 1, 2, 8 and 12 h post-(last) infusion]
Maximum (End of Infusion) Serum Concentration (Cinf) of Loading Dose AZD9773 Serum Total Fabs (Cohorts 3,4 and 5)
Time frame: Day 1 [PK samples taken pre-dose, the end of each infusion rate and then at 0.5, 1, 2, 8 and 12 h post-(last)infusion]
Time to Reach Cinf (Tmax) of Loading Dose AZD9773 Serum Total Fabs (Cohorts 3, 4 and 5)
Time frame: Day 1 [PK samples taken pre-dose, the end of each infusion rate and then at 0.5, 1, 2, 8 and 12 h post-(last)infusion]
AUC(0-12) of Maintenance Dose AZD9773 Serum Total Fabs (Cohorts 3, 4 and 5)
Time frame: PK samples taken pre-dose of Doses 5,7 and 9, then at 0, 0.5, 1, 2, 8 and 12 h post dose 9 infusion
Cinf of Maintenance Dose AZD9773 Serum Total Fabs (Cohorts 3, 4 and 5)
Time frame: PK samples taken pre-dose of Doses 5,7 and 9, then at 0, 0.5, 1, 2, 8 and 12 h post dose 9 infusion
Tmax of Maintenance Dose AZD9773 Serum Total Fabs (Cohorts 3, 4 and 5)
Time frame: PK samples taken pre-dose of Doses 5,7 and 9, then at 0, 0.5, 1, 2, 8 and 12 h post dose 9 infusion
Number of Patients Below Tumour Necrosis Factor (TNF)-Alpha Limit of Quantification (LOQ) at 24 Hours (n< LOQ)
Time frame: 24 hours

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
AZD9773 Cohort 1 (50 Units/kg)	8	8
AZD9773 Cohort 2 (250 Units/kg)	9	8
AZD9773 Cohort 3 (250/50 Units/kg)	12	7
AZD9773 Cohort 4 (500/100 Units/kg)	10	9
AZD9773 Cohort 5 (750/250 Units/kg)	8	7
Placebo	23	20

Primary outcome: Change From Baseline in Creatinine Values

Time frame: End of study (Day 28). Mean (Full Range). Unit: μmol/L

Measure	AZD9773 Cohort 1 (50 Units/kg) n = 5	AZD9773 Cohort 2 (250 Units/kg) n = 4	AZD9773 Cohort 3 (250/50 Units/kg) n = 7	AZD9773 Cohort 4 (500/100 Units/kg) n = 8	AZD9773 Cohort 5 (750/250 Units/kg) n = 6	Placebo n = 15
Value	-78.6 (-239)	-196.8 (-681)	-25.1 (-126)	-10.9 (-68)	159.0 (-89)	-57.4 (-191)

Population analysed: Participants analyzed relates to the number of evaluable patients at the specified time point.

Primary outcome: Change From Baseline in Alanine Aminotransferase Values

Time frame: End of study (Day 28). Mean (Full Range). Unit: μkat/L

Measure	AZD9773 Cohort 1 (50 Units/kg) n = 5	AZD9773 Cohort 2 (250 Units/kg) n = 3	AZD9773 Cohort 3 (250/50 Units/kg) n = 7	AZD9773 Cohort 4 (500/100 Units/kg) n = 7	AZD9773 Cohort 5 (750/250 Units/kg) n = 6	Placebo n = 15
Value	-0.998 (-3.24)	0.017 (-0.25)	-3.133 (-20.62)	-0.520 (-2.05)	-0.825 (-4.53)	-0.111 (-0.79)

Population analysed: Participants analyzed relates to the number of evaluable patients at the specified time point.

Primary outcome: Change From Baseline in Aspartate Aminotransferase Values

Time frame: End of study (Day 28). Mean (Full Range). Unit: μkat/L

Measure	AZD9773 Cohort 1 (50 Units/kg) n = 5	AZD9773 Cohort 2 (250 Units/kg) n = 3	AZD9773 Cohort 3 (250/50 Units/kg) n = 7	AZD9773 Cohort 4 (500/100 Units/kg) n = 7	AZD9773 Cohort 5 (750/250 Units/kg) n = 6	Placebo n = 15
Value	-2.298 (-5.56)	-0.213 (-0.43)	-3.647 (-21.36)	-0.926 (-3.27)	-0.998 (-3.29)	-0.253 (-1.54)

Population analysed: Participants analyzed relates to the number of evaluable patients at the specified time point.

Primary outcome: Change From Baseline in Bilirubin Values

Time frame: End of study (Day 28). Mean (Full Range). Unit: μmol/L

Measure	AZD9773 Cohort 1 (50 Units/kg) n = 5	AZD9773 Cohort 2 (250 Units/kg) n = 3	AZD9773 Cohort 3 (250/50 Units/kg) n = 7	AZD9773 Cohort 4 (500/100 Units/kg) n = 7	AZD9773 Cohort 5 (750/250 Units/kg) n = 6	Placebo n = 15
Value	-11.30 (-17.1)	-13.10 (-34.2)	-10.04 (-49.6)	-23.71 (-71.8)	-2.58 (-29.1)	-10.00 (-37.6)

Population analysed: Participants analyzed relates to the number of evaluable patients at the specified time point.

12 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
AZD9773 Cohort 1 (50 Units/kg)	3 of 8 (37.5%)	8 of 8 (100%)	Not reported
AZD9773 Cohort 2 (250 Units/kg)	6 of 9 (66.7%)	8 of 9 (88.9%)	Not reported
AZD9773 Cohort 3 (250/50 Units/kg)	7 of 12 (58.3%)	11 of 12 (91.7%)	Not reported
AZD9773 Cohort 4 (500/100 Units/kg)	3 of 10 (30%)	7 of 10 (70%)	Not reported
AZD9773 Cohort 5 (750/250 Units/kg)	4 of 8 (50%)	7 of 8 (87.5%)	Not reported
Placebo	13 of 23 (56.5%)	22 of 23 (95.7%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2013.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 23001587Yates 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.

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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.

Steven Simonson, MD study director

AstraZeneca

Wayne Dankner, MD study director

Parexel

26 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 (CytoFab) in people with Severe Sepsis, run by AstraZeneca at 26 sites in United States.

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 4 inclusion and 5 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 22 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 sites in United States. 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?

Change From Baseline in Creatinine Values (time frame: End of study (Day 28)). The study lists 12 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 NCT00615017, 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 22 Aug 2013.