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

Primary Purpose

Severe Sepsis, Septic Shock

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
BMS-936559
Placebo
Sponsored by
Bristol-Myers Squibb
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Severe Sepsis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Uc Davis Medical Center
  • Local Institution
  • University Of Florida
  • Emory University
  • Osf Saint Francis Medical Center
  • Massachusetts General Hospital
  • Baystate Medical Center
  • University of Michigan, Division of Acute Care Surgery
  • Washington University School Of Medicine
  • The Ohio State University
  • St. Vincent'S Medical Center
  • UPMC
  • Local Institution

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Other

Arm Label

BMS-936559

Placebo

Arm Description

BMS-936559 Intravenous infusion on specified days

Placebo on specified days

Outcomes

Primary Outcome Measures

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
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
Part 1: Tolerability of BMS-936559 in subjects with severe sepsis
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
Part 2: All-cause mortality within 90 days of study drug administration

Secondary Outcome Measures

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

Full Information

First Posted
October 13, 2015
Last Updated
September 14, 2017
Sponsor
Bristol-Myers Squibb
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1. Study Identification

Unique Protocol Identification Number
NCT02576457
Brief Title
Safety, Pharmacokinetics and Pharmacodynamics of BMS-936559 in Severe Sepsis
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2017
Overall Recruitment Status
Terminated
Why Stopped
Business Objectives Have Changed
Study Start Date
December 2, 2015 (Actual)
Primary Completion Date
March 15, 2017 (Actual)
Study Completion Date
March 15, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bristol-Myers Squibb

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Severe Sepsis, Septic Shock

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
35 (Actual)

8. Arms, Groups, and Interventions

Arm Title
BMS-936559
Arm Type
Experimental
Arm Description
BMS-936559 Intravenous infusion on specified days
Arm Title
Placebo
Arm Type
Other
Arm Description
Placebo on specified days
Intervention Type
Biological
Intervention Name(s)
BMS-936559
Intervention Type
Other
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
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
Description
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
Time Frame
Approximately 3 months
Title
Part 1: Tolerability of BMS-936559 in subjects with severe sepsis
Description
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
Time Frame
Approximately 3 months
Title
Part 2: All-cause mortality within 90 days of study drug administration
Time Frame
Approximately 3 months
Secondary Outcome Measure Information:
Title
Maximum observed serum concentration (Cmax) of BMS-936559
Time Frame
Approximately 3 months
Title
Time of maximum observed serum concentration (Tmax) of BMS-936559
Time Frame
Approximately 3 months
Title
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
Title
Area under the serum concentration-time curve from time zero extrapolated to infinite time (AUC(INF)) of BMS-936559
Time Frame
Approximately 3 months
Title
Total Body Clearance (CLT) of BMS-936559
Time Frame
Approximately 3 months
Title
Volume of distribution at steady state (Vss) of BMS-936559
Time Frame
Approximately 3 months
Title
Terminal serum half-life (T-HALF) of BMS-936559
Time Frame
Approximately 3 months
Title
Receptor occupancy based on PD-L1 receptor occupancy levels
Time Frame
Approximately 3 months
Title
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
Title
Immune system function based on absolute lymphocyte counts at planned sampling timepoints
Time Frame
Approximately 3 months
Title
Immune system function based on lipopolysaccharide (LPS)-induced whole blood TNFalpha production levels at planned sampling timepoints
Time Frame
Approximately 3 months
Title
Organ dysfunction measured by organ support-free days (OSFDs)
Description
OSFD is defined as the last period of organ support-free duration during the index hospitalization stay prior to discharge.
Time Frame
Approximately 3 months
Title
Organ dysfunction measured by proportion of OSFDs during index hospitalization
Description
OSFD is defined as the last period of organ support-free duration during the index hospitalization stay prior to discharge.
Time Frame
Approximately 3 months
Title
Duration of mechanical ventilation, vasopressor use, and/or dialysis use separately during the index hospitalization
Time Frame
Approximately 3 months
Title
Incidence of secondary infections (as adjudicated by a clinical committee) up to 90 days post administration of BMS-936559
Time Frame
Approximately 3 months
Title
All-cause mortality at 28 days, 90 days, and 1 year after study drug administration
Description
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.
Time Frame
Approximately 3 months
Title
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
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
Uc Davis Medical Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Local Institution
City
Denver
State/Province
Colorado
ZIP/Postal Code
80204
Country
United States
Facility Name
University Of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Osf Saint Francis Medical Center
City
Peoria
State/Province
Illinois
ZIP/Postal Code
61637
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Baystate Medical Center
City
Springfield
State/Province
Massachusetts
ZIP/Postal Code
01199
Country
United States
Facility Name
University of Michigan, Division of Acute Care Surgery
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109-5033
Country
United States
Facility Name
Washington University School Of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
The Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
St. Vincent'S Medical Center
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43603
Country
United States
Facility Name
UPMC
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15261-2500
Country
United States
Facility Name
Local Institution
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
30747773
Citation
Hotchkiss RS, Colston E, Yende S, Angus DC, Moldawer LL, Crouser ED, Martin GS, Coopersmith CM, Brakenridge S, Mayr FB, Park PK, Ye J, Catlett IM, Girgis IG, Grasela DM. Immune Checkpoint Inhibition in Sepsis: A Phase 1b Randomized, Placebo-Controlled, Single Ascending Dose Study of Antiprogrammed Cell Death-Ligand 1 Antibody (BMS-936559). Crit Care Med. 2019 May;47(5):632-642. doi: 10.1097/CCM.0000000000003685.
Results Reference
derived
Links:
URL
http://bms.com/studyconnect/Pages/home.aspx
Description
BMS Clinical Trial Patient Recruiting

Learn more about this trial

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

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