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

Phase 1

Terminated

• Conditions: Severe Sepsis; Septic Shock
• Interventions: Other: Placebo; Biological: BMS-936559

• Registration Number: NCT02576457
• Lead Sponsor: Bristol-Myers Squibb

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-10-13
• Study First Submitted QC: 2015-10-14
• Study First Posted: 2015-10-15
• Study Start: 2015-12-02
• Primary Completion: 2017-03-15
• Study Completion: 2017-03-15
• Status Verified: 2017-09
• Last Update Submitted: 2017-09-14
• Last Update Posted: 2017-09-15

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 35

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

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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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo on specified days
BMS-936559	BMS-936559	BMS-936559 Intravenous infusion on specified days

Primary Outcome Measures

Name	Time	Method
Part 2: All-cause mortality within 90 days of study drug administration	Approximately 3 months
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	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
Part 1: Tolerability of BMS-936559 in subjects with severe sepsis	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

Secondary Outcome Measures

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

Trial Locations

Locations (12)

Uc Davis Medical Center; 🇺🇸 Sacramento, California, United States

Local Institution; 🇺🇸 Seattle, Washington, United States

Emory University; 🇺🇸 Atlanta, Georgia, United States

Osf Saint Francis Medical Center; 🇺🇸 Peoria, Illinois, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

University of Michigan, Division of Acute Care Surgery; 🇺🇸 Ann Arbor, Michigan, United States

UPMC; 🇺🇸 Pittsburgh, Pennsylvania, United States

St. Vincent'S Medical Center; 🇺🇸 Toledo, Ohio, United States

University Of Florida; 🇺🇸 Gainesville, Florida, United States

The Ohio State University; 🇺🇸 Columbus, Ohio, United States

Washington University School Of Medicine; 🇺🇸 Saint Louis, Missouri, United States

Baystate Medical Center; 🇺🇸 Springfield, Massachusetts, United States