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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Severe Sepsis, Septic Shock

Intervention / Treatment
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* Biological: BMS-936559
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BMS-936559<br>BMS-936559 Intravenous infusion on specified days | Biological: BMS-936559<br> <br> |
| Other: Placebo<br>Placebo on specified days | Other: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| Part 2: All-cause mortality within 90 days of study drug administration |  | Approximately 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed serum concentration (Cmax) of BMS-936559 |  | Approximately 3 months | 
| Time of maximum observed serum concentration (Tmax) of BMS-936559 |  | 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 |  | 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 | 
| Volume of distribution at steady state (Vss) of BMS-936559 |  | Approximately 3 months | 
| Terminal serum half-life (T-HALF) of BMS-936559 |  | Approximately 3 months | 
| Receptor occupancy based on PD-L1 receptor occupancy levels |  | 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 | 
| 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) | OSFD is defined as the last period of organ support-free duration during the index hospitalization stay prior to discharge. | 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. | Approximately 3 months | 
| Duration of mechanical ventilation, vasopressor use, and/or dialysis use separately during the index hospitalization |  | 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 | 
| 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 | 
| Immunogenicity measured by number of subjects having detectable anti-drug antibodies (ADA) at baseline and following administration of BMS-936559. |  | Approximately 3 months | 
| Immunogenicity measured by percentage of subjects having detectable anti-drug antibodies (ADA) at baseline and following administration of BMS-936559. |  | Approximately 3 months |