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

Phase 1TerminatedNCT02576457

Bristol-Myers Squibb35 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Severe Sepsis Septic Shock

Interventions

BMS-936559BIOLOGICAL

PlaceboOTHER

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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)

Locations (13)

Uc Davis Medical Center

Sacramento, California, United States

Local Institution

Denver, Colorado, United States

University Of Florida

Gainesville, Florida, United States

Outcomes

Primary Outcomes

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

Time frame: Approximately 3 months

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

Time frame: Approximately 3 months

Part 2: All-cause mortality within 90 days of study drug administration

Time frame: Approximately 3 months

Secondary Outcomes

Maximum observed serum concentration (Cmax) of BMS-936559

Time frame: Approximately 3 months

Time of maximum observed serum concentration (Tmax) of BMS-936559

Time frame: Approximately 3 months

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

Area under the serum concentration-time curve from time zero extrapolated to infinite time (AUC(INF)) of BMS-936559

Time frame: Approximately 3 months

Total Body Clearance (CLT) of BMS-936559

Data from ClinicalTrials.gov

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Emory University

Atlanta, Georgia, United States

Osf Saint Francis Medical Center

Peoria, Illinois, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Baystate Medical Center

Springfield, Massachusetts, United States

University of Michigan, Division of Acute Care Surgery

Ann Arbor, Michigan, United States

Washington University School Of Medicine

St Louis, Missouri, United States

The Ohio State University

Columbus, Ohio, United States

...and 3 more locations

Time frame: Approximately 3 months

Volume of distribution at steady state (Vss) of BMS-936559

Time frame: Approximately 3 months

Terminal serum half-life (T-HALF) of BMS-936559

Time frame: Approximately 3 months

Receptor occupancy based on PD-L1 receptor occupancy levels

Time frame: Approximately 3 months

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

Immune system function based on absolute lymphocyte counts at planned sampling timepoints

Time frame: Approximately 3 months

Immune system function based on lipopolysaccharide (LPS)-induced whole blood TNFalpha production levels at planned sampling timepoints

Time frame: Approximately 3 months

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.

Time frame: Approximately 3 months

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.

Time frame: Approximately 3 months

Duration of mechanical ventilation, vasopressor use, and/or dialysis use separately during the index hospitalization

Time frame: Approximately 3 months

Incidence of secondary infections (as adjudicated by a clinical committee) up to 90 days post administration of BMS-936559

Time frame: Approximately 3 months

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.

Time frame: Approximately 3 months

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

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