Clinical trial NCT02576457: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: Severe Sepsis
Septic Shock
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2015-10-15
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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)

Primary outcomes:
measure: 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
timeFrame: Approximately 3 months
measure: Part 1: Tolerability of BMS-936559 in subjects with severe sepsis
timeFrame: Approximately 3 months
measure: Part 2: All-cause mortality within 90 days of study drug administration
timeFrame: Approximately 3 months
Secondary outcomes:
measure: Maximum observed serum concentration (Cmax) of BMS-936559
timeFrame: Approximately 3 months
measure: Time of maximum observed serum concentration (Tmax) of BMS-936559
timeFrame: Approximately 3 months
measure: Area under the serum concentration-time curve from time zero to time of last quantifiable concentration (AUC(0-T)) of BMS-936559
timeFrame: Approximately 3 months
measure: Area under the serum concentration-time curve from time zero extrapolated to infinite time (AUC(INF)) of BMS-936559
timeFrame: Approximately 3 months
measure: Total Body Clearance (CLT) of BMS-936559
timeFrame: Approximately 3 months
measure: Volume of distribution at steady state (Vss) of BMS-936559
timeFrame: Approximately 3 months
measure: Terminal serum half-life (T-HALF) of BMS-936559
timeFrame: Approximately 3 months
measure: Receptor occupancy based on PD-L1 receptor occupancy levels
timeFrame: Approximately 3 months
measure: Immune system function based on baseline and post-dosing assessments of mHLA-DR expression on monocytes at planned sampling timepoints
timeFrame: Approximately 3 months
measure: Immune system function based on absolute lymphocyte counts at planned sampling timepoints
timeFrame: Approximately 3 months
measure: Immune system function based on lipopolysaccharide (LPS)-induced whole blood TNFalpha production levels at planned sampling timepoints
timeFrame: Approximately 3 months
measure: Organ dysfunction measured by organ support-free days (OSFDs)
timeFrame: Approximately 3 months
measure: Organ dysfunction measured by proportion of OSFDs during index hospitalization
timeFrame: Approximately 3 months
measure: Duration of mechanical ventilation, vasopressor use, and/or dialysis use separately during the index hospitalization
timeFrame: Approximately 3 months
measure: Incidence of secondary infections (as adjudicated by a clinical committee) up to 90 days post administration of BMS-936559
timeFrame: Approximately 3 months
measure: All-cause mortality at 28 days, 90 days, and 1 year after study drug administration
timeFrame: Approximately 3 months
measure: Immunogenicity measured by number of subjects having detectable anti-drug antibodies (ADA) at baseline and following administration of BMS-936559.
timeFrame: Approximately 3 months
measure: Immunogenicity measured by percentage of subjects having detectable anti-drug antibodies (ADA) at baseline and following administration of BMS-936559.
timeFrame: Approximately 3 months
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: Uc Davis Medical Center
state: California
city: Denver
country: United States
facility: Local Institution
state: Colorado
city: Gainesville
country: United States
facility: University Of Florida
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Peoria
country: United States
facility: Osf Saint Francis Medical Center
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan, Division of Acute Care Surgery
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School Of Medicine
state: Missouri
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Toledo
country: United States
facility: St. Vincent'S Medical Center
state: Ohio
city: Pittsburgh
country: United States
facility: UPMC
state: Pennsylvania
city: Seattle
country: United States
facility: Local Institution
state: Washington
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol Myers Squibb
role: STUDY_DIRECTOR
References:
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.