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

Septic Shock Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02576457
• Other study ID #: AI471-049
• Status: Terminated
• Phase: Phase 1
• First received: October 13, 2015
• Last updated: September 14, 2017
• Start date: December 2, 2015
• Est. completion date: March 15, 2017

Study information

• Verified date: September 2017
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 35
• Est. completion date: March 15, 2017
• Est. primary completion date: March 15, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Sepsis
• Septic Shock
• Severe Sepsis
• Shock, Septic
• Toxemia

Intervention

Biological:
• BMS-936559

Other:
• Placebo

Locations

Country	Name	City	State
United States	University of Michigan, Division of Acute Care Surgery	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	The Ohio State University	Columbus	Ohio
United States	Local Institution	Denver	Colorado
United States	University Of Florida	Gainesville	Florida
United States	Osf Saint Francis Medical Center	Peoria	Illinois
United States	UPMC	Pittsburgh	Pennsylvania
United States	Uc Davis Medical Center	Sacramento	California
United States	Washington University School Of Medicine	Saint Louis	Missouri
United States	Local Institution	Seattle	Washington
United States	Baystate Medical Center	Springfield	Massachusetts
United States	St. Vincent'S Medical Center	Toledo	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Approximately 3 months
Primary	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	Approximately 3 months
Primary	Part 2: All-cause mortality within 90 days of study drug administration		Approximately 3 months
Secondary	Maximum observed serum concentration (Cmax) of BMS-936559		Approximately 3 months
Secondary	Time of maximum observed serum concentration (Tmax) of BMS-936559		Approximately 3 months
Secondary	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
Secondary	Area under the serum concentration-time curve from time zero extrapolated to infinite time (AUC(INF)) of BMS-936559		Approximately 3 months
Secondary	Total Body Clearance (CLT) of BMS-936559		Approximately 3 months
Secondary	Volume of distribution at steady state (Vss) of BMS-936559		Approximately 3 months
Secondary	Terminal serum half-life (T-HALF) of BMS-936559		Approximately 3 months
Secondary	Receptor occupancy based on PD-L1 receptor occupancy levels		Approximately 3 months
Secondary	Immune system function based on baseline and post-dosing assessments of mHLA-DR expression on monocytes at planned sampling timepoints		Approximately 3 months
Secondary	Immune system function based on absolute lymphocyte counts at planned sampling timepoints		Approximately 3 months
Secondary	Immune system function based on lipopolysaccharide (LPS)-induced whole blood TNFalpha production levels at planned sampling timepoints		Approximately 3 months
Secondary	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.	Approximately 3 months
Secondary	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.	Approximately 3 months
Secondary	Duration of mechanical ventilation, vasopressor use, and/or dialysis use separately during the index hospitalization		Approximately 3 months
Secondary	Incidence of secondary infections (as adjudicated by a clinical committee) up to 90 days post administration of BMS-936559		Approximately 3 months
Secondary	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.	Approximately 3 months
Secondary	Immunogenicity measured by number of subjects having detectable anti-drug antibodies (ADA) at baseline and following administration of BMS-936559.		Approximately 3 months
Secondary	Immunogenicity measured by percentage of subjects having detectable anti-drug antibodies (ADA) at baseline and following administration of BMS-936559.		Approximately 3 months

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting
•   FDA Safety Alerts and Recalls
•   Investigator Inquiry Form