A Study of Nivolumab Safety and Pharmacokinetics in Patients With Severe Sepsis or Septic Shock.

Study Overview
=================
Brief Summary
-----------------
A study to evaluate the safety, tolerability and pharmacokinetics of Nivolumab in participants with severe sepsis or septic shock.

Official Title
-----------------
Randomized, Double-Blind, Parallel Group Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BMS-936558 (Nivolumab) in Participants With Severe Sepsis or Septic Shock.

Conditions
-----------------
Severe Sepsis

Intervention / Treatment
-----------------
* Biological: Nivolumab


Participation Criteria
=================
Eligibility Criteria
-----------------
For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: Men and women ages ≥ 18 years old Documented or suspected infection Severe sepsis or septic shock for at least 24 hours Sepsis-induced immunosuppression In Intensive Care Unit (ICU) with no plans to discharge in next 24 hours Exclusion Criteria: Previous episode of severe sepsis or septic shock with ICU admission during the current hospitalization Autoimmune disease Organ or bone marrow transplant Cancer treatment in the past 6 weeks 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); Chronic hepatitis B virus (HBV) infection and not on treatment Other protocol defined inclusion/exclusion criteria could apply

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nivolumab 1<br>Dose 1 | Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: BMS-936558;|
| Experimental: Nivolumab 2<br>Dose 2 | Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: BMS-936558;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Incidence Rates of Serious Adverse Events (SAEs), Adverse Events (AEs), Immune-mediated AEs, AEs Leading to Discontinuation, and Deaths |  | Screening, day -1, day 1 and subsequent days after, up to 90 days | 
| Composite of Vital Signs and Electrocardiogram (ECG) | Includes body temperature, respiratory rate, blood pressure and heart rate. Blood pressure and heart rate should be measured after the participant has been resting quietly for at least 5 minutes. | Screening up to 90 days (Discharge) | 
| Peak Nivolumab Serum Concentration (Cmax) | Participants peak nivolumab serum concentration | Day 1 and subsequent days after, up to 90 days | 
| Trough Nivolumab Serum Concentration (Cmin) | Participant trough nivolumab serum concentration | Day 1 and subsequent days after, up to 90 days | 
| Average Nivolumab Serum Concentration (Cavg) | Participant average nivolumab serum concentration | Day 1 and subsequent days after, up to 90 days | 
| Time of Maximum Observed Concentration (Tmax) | Participant observed time of maximum concentration | Day 1 and subsequent days after, up to 90 days | 
| Area Under the Serum Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration [AUC(0-T)] | Area under the serum concentration-time curve from time zero to time of last quantifiable concentration | Day 1 and subsequent days after, up to 90 days | 
| Total Clearance (CLT) | Total clearance of serum concentration of nivolumab | Day 1 and subsequent days after, up to 90 days | 
| Volume of Distribution (Vd) | Vlume of distribution of nivolumab serum concentration | Day 1 and subsequent days after, up to 90 days | 
| Half-life (T1/2) | Half-Life of nivolumab derived from serum concentration | Day 1 and subsequent days after, up to 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Receptor Occupancy | Receptor occupancy on T cells at baseline and after study treatment administration at planned sampling time points | Day 1 and up to day 90 (discharge) | 
| Number of Participants With Detectable Anti-nivolumab Antibodies | Participant with positive anti-drug antibody detection | Baseline and subsequent days after, up to 90 days | 
| Number of Participants With Any Detectable Anti-drug Antibodies |  | Baseline and subsequent days after, up to 90 days |