Septic Shock, Severe Sepsis
Conditions
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.
Interventions
BIOLOGICALBMS-936559
OTHERPlacebo
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Part 2: All-cause mortality within 90 days of study drug administration | Approximately 3 months | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| Maximum observed serum concentration (Cmax) of BMS-936559 | 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. |
| 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. |
| 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 | 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 | — |
| Immunogenicity measured by percentage of subjects having detectable anti-drug antibodies (ADA) at baseline and following administration of BMS-936559. | Approximately 3 months | — |
| Immune system function based on lipopolysaccharide (LPS)-induced whole blood TNFalpha production levels at planned sampling timepoints | 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 | — |
Countries
United States
Outcome results
None listed