Clinical trial NCT02960854: A Study of Nivolumab Safety and Pharmacokinetics in Patients 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Severe Sepsis
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2016-11-10
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: A study to evaluate the safety, tolerability and pharmacokinetics of Nivolumab in participants with severe sepsis or septic shock.


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

Primary outcomes:
measure: Percentage of Incidence Rates of Serious Adverse Events (SAEs), Adverse Events (AEs), Immune-mediated AEs, AEs Leading to Discontinuation, and Deaths
timeFrame: Screening, day -1, day 1 and subsequent days after, up to 90 days
measure: Composite of Vital Signs and Electrocardiogram (ECG)
timeFrame: Screening up to 90 days (Discharge)
measure: Peak Nivolumab Serum Concentration (Cmax)
timeFrame: Day 1 and subsequent days after, up to 90 days
measure: Trough Nivolumab Serum Concentration (Cmin)
timeFrame: Day 1 and subsequent days after, up to 90 days
measure: Average Nivolumab Serum Concentration (Cavg)
timeFrame: Day 1 and subsequent days after, up to 90 days
measure: Time of Maximum Observed Concentration (Tmax)
timeFrame: Day 1 and subsequent days after, up to 90 days
measure: Area Under the Serum Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration [AUC(0-T)]
timeFrame: Day 1 and subsequent days after, up to 90 days
measure: Total Clearance (CLT)
timeFrame: Day 1 and subsequent days after, up to 90 days
measure: Volume of Distribution (Vd)
timeFrame: Day 1 and subsequent days after, up to 90 days
measure: Half-life (T1/2)
timeFrame: Day 1 and subsequent days after, up to 90 days
Secondary outcomes:
measure: Receptor Occupancy
timeFrame: Day 1 and up to day 90 (discharge)
measure: Number of Participants With Detectable Anti-nivolumab Antibodies
timeFrame: Baseline and subsequent days after, up to 90 days
measure: Number of Participants With Any Detectable Anti-drug Antibodies
timeFrame: Baseline and subsequent days after, up to 90 days
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: Uc Davis Medical Center
state: California
city: Colorado Springs
country: United States
facility: Univ. Of Colorado Health
state: Colorado
city: Denver
country: United States
facility: Denver Health Medical Center
state: Colorado
city: Gainesville
country: United States
facility: University Of Florida
state: Florida
city: Atlanta
country: United States
facility: Pulmonary And Critical Care Of Atlanta
state: Georgia
city: Peoria
country: United States
facility: Osf Saint Francis Medical Center
state: Illinois
city: Lexington
country: United States
facility: University Of Kentucky
state: Kentucky
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center (BIDMC)
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan, Division of Acute Care Surgery
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School Of Medicine
state: Missouri
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Pittsburgh
country: United States
facility: UPMC
state: Pennsylvania
city: Seattle
country: United States
facility: Harborview Medical Center
state: Washington
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Hotchkiss RS, Colston E, Yende S, Crouser ED, Martin GS, Albertson T, Bartz RR, Brakenridge SC, Delano MJ, Park PK, Donnino MW, Tidswell M, Mayr FB, Angus DC, Coopersmith CM, Moldawer LL, Catlett IM, Girgis IG, Ye J, Grasela DM. Immune checkpoint inhibition in sepsis: a Phase 1b randomized study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of nivolumab. Intensive Care Med. 2019 Oct;45(10):1360-1371. doi: 10.1007/s00134-019-05704-z. Epub 2019 Oct 1.