Safety, Pharmacokinetics and Pharmacodynamics of BMS-936559 in Severe Sepsis

Study Description

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

The purpose of this study is to determine whether BMS-936559 is safe and has the desired pharmacologic activity in patients who have severe sepsis.

Condition or disease	Intervention/treatment	Phase
Severe Sepsis; Septic Shock	Biological: BMS-936559; Other: Placebo	Phase 1

Study Design

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	35 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	A Phase 1b/2a, Randomized, Double-Blinded, Placebo-Controlled, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BMS-936559 in Subjects With Severe Sepsis
Actual Study Start Date :	December 2, 2015
Actual Primary Completion Date :	March 15, 2017
Actual Study Completion Date :	March 15, 2017

Arms and Interventions

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Experimental: BMS-936559; BMS-936559 Intravenous infusion on specified days	Biological: BMS-936559
Placebo; Placebo on specified days	Other: Placebo

Outcome Measures

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. Part 1: Safety of BMS-936559 in subjects with severe sepsis - measured by the incidence rates of death, AEs, SAEs, AEs leading to discontinuation, AEs of special interest and laboratory abnormalities [ Time Frame: Approximately 3 months ]
   Safety will be measured by the incidence rates of death, Adverse event (AEs), Serious adverse event (SAEs), AEs leading to discontinuation, AEs of special interest (identified from PD-L1 oncology trial), and laboratory abnormalities
2. Part 1: Tolerability of BMS-936559 in subjects with severe sepsis [ Time Frame: Approximately 3 months ]
   Tolerability will be measured by the incidence rates of death, AEs, SAEs, AEs leading to discontinuation, AEs of special interest (identified from PD-L1 oncology trial), and laboratory abnormalities
3. Part 2: All-cause mortality within 90 days of study drug administration [ Time Frame: Approximately 3 months ]

Secondary Outcome Measures :

1. Maximum observed serum concentration (Cmax) of BMS-936559 [ Time Frame: Approximately 3 months ]
2. Time of maximum observed serum concentration (Tmax) of BMS-936559 [ Time Frame: Approximately 3 months ]
3. Area under the serum concentration-time curve from time zero to time of last quantifiable concentration (AUC(0-T)) of BMS-936559 [ Time Frame: Approximately 3 months ]
4. Area under the serum concentration-time curve from time zero extrapolated to infinite time (AUC(INF)) of BMS-936559 [ Time Frame: Approximately 3 months ]
5. Total Body Clearance (CLT) of BMS-936559 [ Time Frame: Approximately 3 months ]
6. Volume of distribution at steady state (Vss) of BMS-936559 [ Time Frame: Approximately 3 months ]
7. Terminal serum half-life (T-HALF) of BMS-936559 [ Time Frame: Approximately 3 months ]
8. Receptor occupancy based on PD-L1 receptor occupancy levels [ Time Frame: Approximately 3 months ]
9. Immune system function based on baseline and post-dosing assessments of mHLA-DR expression on monocytes at planned sampling timepoints [ Time Frame: Approximately 3 months ]
10. Immune system function based on absolute lymphocyte counts at planned sampling timepoints [ Time Frame: Approximately 3 months ]
11. Immune system function based on lipopolysaccharide (LPS)-induced whole blood TNFalpha production levels at planned sampling timepoints [ Time Frame: Approximately 3 months ]
12. Organ dysfunction measured by organ support-free days (OSFDs) [ Time Frame: Approximately 3 months ]
    OSFD is defined as the last period of organ support-free duration during the index hospitalization stay prior to discharge.
13. Organ dysfunction measured by proportion of OSFDs during index hospitalization [ Time Frame: Approximately 3 months ]
    OSFD is defined as the last period of organ support-free duration during the index hospitalization stay prior to discharge.
14. Duration of mechanical ventilation, vasopressor use, and/or dialysis use separately during the index hospitalization [ Time Frame: Approximately 3 months ]
15. Incidence of secondary infections (as adjudicated by a clinical committee) up to 90 days post administration of BMS-936559 [ Time Frame: Approximately 3 months ]
16. All-cause mortality at 28 days, 90 days, and 1 year after study drug administration [ Time Frame: Approximately 3 months ]

    All-cause mortality at 28 days, 90 days, and 1 year post administration of BMS-936559.

    Time to death will also be used to assess the treatment effect.

17. Immunogenicity measured by number of subjects having detectable anti-drug antibodies (ADA) at baseline and following administration of BMS-936559. [ Time Frame: Approximately 3 months ]
18. Immunogenicity measured by percentage of subjects having detectable anti-drug antibodies (ADA) at baseline and following administration of BMS-936559. [ Time Frame: Approximately 3 months ]

Eligibility Criteria

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Severe sepsis or septic shock for at least 24 hours
• Documented or suspected infection
• Sepsis-induced immunosuppression
• Men and women ≥ 18 years old

Exclusion Criteria:

• Autoimmune disease
• Organ transplant or bone marrow transplant
• Cancer treated in the past 6 months
• Hepatitis B virus (HBV) Infection
• Human Immunodeficiency Virus (HIV) infection and not on therapy prior to this episode of sepsis
• Hepatitis C virus (HCV) infection and still has virus (not cured)

Contacts and Locations

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United States, California
Uc Davis Medical Center
Sacramento, California, United States, 95817
United States, Colorado
Local Institution
Denver, Colorado, United States, 80204
United States, Florida
University Of Florida
Gainesville, Florida, United States, 32610
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
United States, Illinois
Osf Saint Francis Medical Center
Peoria, Illinois, United States, 61637
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Baystate Medical Center
Springfield, Massachusetts, United States, 01199
United States, Michigan
University of Michigan, Division of Acute Care Surgery
Ann Arbor, Michigan, United States, 48109-5033
United States, Missouri
Washington University School Of Medicine
Saint Louis, Missouri, United States, 63110
United States, Ohio
The Ohio State University
Columbus, Ohio, United States, 43210
St. Vincent'S Medical Center
Toledo, Ohio, United States, 43603
United States, Pennsylvania
UPMC
Pittsburgh, Pennsylvania, United States, 15261-2500
United States, Washington
Local Institution
Seattle, Washington, United States, 98104

Sponsors and Collaborators

Bristol-Myers Squibb

Investigators

Study Director:	Bristol Myers Squibb	Bristol-Myers Squibb

More Information

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

FDA Safety Alerts and Recalls 

BMS Clinical Trial Patient Recruiting 

Investigator Inquiry Form 

Responsible Party:	Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT02576457 History of Changes
Other Study ID Numbers:	AI471-049
First Posted:	October 15, 2015
Last Update Posted:	September 15, 2017
Last Verified:	September 2017

Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

Additional relevant MeSH terms:

Sepsis; Toxemia; Shock, Septic; Infection	Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Shock