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CompletedNCT02960854Updated Apr 23, 2019Results posted

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

A Phase 1 interventional study of Nivolumab in Severe Sepsis, sponsored by Bristol-Myers Squibb. Completed at 16 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-04-23.

Sponsored by Bristol-Myers Squibb · Phase 1, Interventional, and Other

Phase
Phase 1
Study type
Interventional
Enrollment
38
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

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

02

Conditions studied

  • Severe Sepsis

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03

In context

Sepsis

1,899 studies on the registry are indexed under Sepsis; 462 are open to participants now.

This study's enrollment of 38 is below the median of 105 across 896 interventional studies indexed under Sepsis.

Browse Sepsis studies →

Lead sponsor

Bristol-Myers Squibb is the lead sponsor of 1,538 studies on the registry; 116 are open to participants now.

Of its 429 completed or terminated interventional studies of FDA-regulated products, 223 (52%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com

Inclusion criteria

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

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

05

Study design

Phase
Phase 1
Primary purpose
Other
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
38 participants (actual)

Study arms

  • Experimental
    Nivolumab 1

    Dose 1

    Biological: Nivolumab

  • Experimental
    Nivolumab 2

    Dose 2

    Biological: Nivolumab

Interventions

  • BiologicalNivolumab

    Specified dose on specified days

    Also known as: BMS-936558

06

What researchers measure

Primary outcomes

  1. Percentage of Incidence Rates of Serious Adverse Events (SAEs), Adverse Events (AEs), Immune-mediated AEs, AEs Leading to Discontinuation, and Deaths

    Time frame: Screening, day -1, day 1 and subsequent days after, up to 90 days

  2. 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.

    Time frame: Screening up to 90 days (Discharge)

  3. Peak Nivolumab Serum Concentration (Cmax)

    Participants peak nivolumab serum concentration

    Time frame: Day 1 and subsequent days after, up to 90 days

  4. Trough Nivolumab Serum Concentration (Cmin)

    Participant trough nivolumab serum concentration

    Time frame: Day 1 and subsequent days after, up to 90 days

  5. Average Nivolumab Serum Concentration (Cavg)

    Participant average nivolumab serum concentration

    Time frame: Day 1 and subsequent days after, up to 90 days

  6. Time of Maximum Observed Concentration (Tmax)

    Participant observed time of maximum concentration

    Time frame: Day 1 and subsequent days after, up to 90 days

  7. 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

    Time frame: Day 1 and subsequent days after, up to 90 days

  8. Total Clearance (CLT)

    Total clearance of serum concentration of nivolumab

    Time frame: Day 1 and subsequent days after, up to 90 days

  9. Volume of Distribution (Vd)

    Vlume of distribution of nivolumab serum concentration

    Time frame: Day 1 and subsequent days after, up to 90 days

  10. Half-life (T1/2)

    Half-Life of nivolumab derived from serum concentration

    Time frame: Day 1 and subsequent days after, up to 90 days

Secondary outcomes

  1. Receptor Occupancy

    Receptor occupancy on T cells at baseline and after study treatment administration at planned sampling time points

    Time frame: Day 1 and up to day 90 (discharge)

  2. Number of Participants With Detectable Anti-nivolumab Antibodies

    Participant with positive anti-drug antibody detection

    Time frame: Baseline and subsequent days after, up to 90 days

  3. Number of Participants With Any Detectable Anti-drug Antibodies

    Time frame: Baseline and subsequent days after, up to 90 days

07

Results

Posted Apr 4, 2019

Participant flow

Participant flow — Overall Study
MilestoneNivolumab (480 mg)Nivolumab (960 mg)
Started1516
Completed87
Not completed79
Withdrew: Not disclosed22
Withdrew: Subject no longer meets study criteria10
Withdrew: Subject withdrew consent01
Withdrew: Death46

Outcome measures

PrimaryPercentage of Incidence Rates of Serious Adverse Events (SAEs), Adverse Events (AEs), Immune-mediated AEs, AEs Leading to Discontinuation, and Deaths
Time frame:
Screening, day -1, day 1 and subsequent days after, up to 90 days
Reported as:
Number · Percentage
Percentage of Incidence Rates of Serious Adverse Events (SAEs), Adverse Events (AEs), Immune-mediated AEs, AEs Leading to Discontinuation, and Deaths
PercentageNivolumab (480 mg)Nivolumab (960 mg)
Serious Adverse Events (SAEs)6.743.8
Adverse Events (AEs)93.387.5
Immune-Mediated Adverse Events53.381.3
AEs leading to discontinuation0.00.0
Deaths40.038.7
PrimaryComposite 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.

Time frame:
Screening up to 90 days (Discharge)
Reported as:
Mean · Percentage
Composite of Vital Signs and Electrocardiogram (ECG)
PercentageNivolumab (480 mg)Nivolumab (960 mg)
ECG Change from Baseline (Discharge)-18.0 ± 31.68-29.0 ± 3.46
Vital Signs - Diastolic Pressure (mmHg) Screening61.5 ± 20.3758.5 ± 9.00
Vital Signs - Systolic Pressure (mmHg) Screening116.5 ± 21.48105.5 ± 14.65
Vital Signs - Heart Rate (beats/min) Screening80.1 ± 21.3494.6 ± 16.64
Vital Signs - Resp. Rate (breaths/min) Screening23.0 ± 6.0824.4 ± 8.83
Vital Signs - Temperature (C) Screening37.19 ± 0.7937.11 ± 0.77
Vital Signs - Diastolic Pressure (mmHg) Discharge79.7 ± 16.4970.5 ± 16.28
Vital Signs - Systolic Pressure (mmHg) Discharge129.0 ± 25.06110.0 ± 16.47
Vital Signs - Heart Rate (beats/min) Discharge85.3 ± 18.8986.5 ± 19.76
Vital Signs - Resp. Rate (breaths/min) Discharge18.8 ± 2.7117.5 ± 3.32
Vital Signs - Temperature (C) Discharge36.60 ± 0.27636.90 ± 0.337
PrimaryPeak Nivolumab Serum Concentration (Cmax)

Participants peak nivolumab serum concentration

Time frame:
Day 1 and subsequent days after, up to 90 days
Reported as:
Geometric mean · ug/mL
Peak Nivolumab Serum Concentration (Cmax)
ug/mLNivolumab (480 mg)Nivolumab (960 mg)
Peak Nivolumab Serum Concentration (Cmax)123 ± 85.4246 ± 85.4
PrimaryTrough Nivolumab Serum Concentration (Cmin)

Participant trough nivolumab serum concentration

Time frame:
Day 1 and subsequent days after, up to 90 days
Reported as:
Geometric mean · ug/mL
Trough Nivolumab Serum Concentration (Cmin)
ug/mLNivolumab (480 mg)Nivolumab (960 mg)
Trough Nivolumab Serum Concentration (Cmin)21.6 ± 3943.2 ± 39
PrimaryAverage Nivolumab Serum Concentration (Cavg)

Participant average nivolumab serum concentration

Time frame:
Day 1 and subsequent days after, up to 90 days
Reported as:
Geometric mean · ug/mL
Average Nivolumab Serum Concentration (Cavg)
ug/mLNivolumab (480 mg)Nivolumab (960 mg)
Average Nivolumab Serum Concentration (Cavg)42.7 ± 28.585.4 ± 28.5
PrimaryTime of Maximum Observed Concentration (Tmax)

Participant observed time of maximum concentration

Time frame:
Day 1 and subsequent days after, up to 90 days
Reported as:
Median · hours
Time of Maximum Observed Concentration (Tmax)
hoursNivolumab (480 mg)Nivolumab (960 mg)
Time of Maximum Observed Concentration (Tmax)1.67 (1.47 to 24.3)1.53 (1.37 to 48.0)
PrimaryArea 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

Time frame:
Day 1 and subsequent days after, up to 90 days
Reported as:
Geometric mean · h*ug/mL
Area Under the Serum Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration [AUC(0-T)]
h*ug/mLNivolumab (480 mg)Nivolumab (960 mg)
Area Under the Serum Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration [AUC(0-T)]18099 ± 5132130 ± 83
PrimaryTotal Clearance (CLT)

Total clearance of serum concentration of nivolumab

Time frame:
Day 1 and subsequent days after, up to 90 days
Reported as:
Geometric mean · L/h
Total Clearance (CLT)
L/hNivolumab (480 mg)Nivolumab (960 mg)
Total Clearance (CLT)0.025 ± 500.027 ± 85
PrimaryVolume of Distribution (Vd)

Vlume of distribution of nivolumab serum concentration

Time frame:
Day 1 and subsequent days after, up to 90 days
Reported as:
Geometric mean · L
Volume of Distribution (Vd)
LNivolumab (480 mg)Nivolumab (960 mg)
Volume of Distribution (Vd)12.0 ± 4213.3 ± 54
PrimaryHalf-life (T1/2)

Half-Life of nivolumab derived from serum concentration

Time frame:
Day 1 and subsequent days after, up to 90 days
Reported as:
Mean · hours
Half-life (T1/2)
hoursNivolumab (480 mg)Nivolumab (960 mg)
Half-life (T1/2)353 ± 126.5378 ± 189.6
SecondaryReceptor Occupancy

Receptor occupancy on T cells at baseline and after study treatment administration at planned sampling time points

Time frame:
Day 1 and up to day 90 (discharge)
Reported as:
Mean · Percentage
Receptor Occupancy
PercentageNivolumab (480 mg)Nivolumab (960 mg)
Baseline0.00 ± 0.000.00 ± 0.00
Study Discharge81.272 ± 27.6971.14 ± 34.83
SecondaryNumber of Participants With Detectable Anti-nivolumab Antibodies

Participant with positive anti-drug antibody detection

Time frame:
Baseline and subsequent days after, up to 90 days
Reported as:
Number · Percentage
Number of Participants With Detectable Anti-nivolumab Antibodies
PercentageNivolumab (480 mg)Nivolumab (960 mg)
Number of Participants With Detectable Anti-nivolumab Antibodies73.375.0
SecondaryNumber of Participants With Any Detectable Anti-drug Antibodies
Time frame:
Baseline and subsequent days after, up to 90 days
Reported as:
Number · Percentage
Number of Participants With Any Detectable Anti-drug Antibodies
PercentageNivolumab (480 mg)Nivolumab (960 mg)
Number of Participants With Any Detectable Anti-drug Antibodies26.756.3

Adverse events

Collected over Adverse events (AEs) and serious adverse events (SAEs) were collected from Day 1 following single dose of nivolumab, up until Day 90.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
NIVOLUMAB 480mg4/15 (26.7%)1/15 (6.7%)14/15 (93.3%)
NIVOLUMAB 960mg6/16 (37.5%)7/16 (43.8%)14/16 (87.5%)
Most frequent serious events
Showing 10 of 14
Most frequent serious events
EventNIVOLUMAB 480mgNIVOLUMAB 960mg
AnaemiaBlood and lymphatic system disorders0/152/16
Intra-abdominal haemorrhageGastrointestinal disorders1/150/16
Abdominal abscessInfections and infestations1/150/16
Disseminated intravascular coagulationBlood and lymphatic system disorders0/151/16
ThrombocytopeniaBlood and lymphatic system disorders0/151/16
Cardiac arrestCardiac disorders0/151/16
Gastrointestinal haemorrhageGastrointestinal disorders0/151/16
MegacolonGastrointestinal disorders0/151/16
Multiple organ dysfunction syndromeGeneral disorders0/151/16
UrosepsisInfections and infestations0/151/16
Most frequent other events
Showing 10 of 230
Most frequent other events
EventNIVOLUMAB 480mgNIVOLUMAB 960mg
AnaemiaBlood and lymphatic system disorders6/158/16
HypotensionVascular disorders6/154/16
PyrexiaGeneral disorders5/156/16
DiarrhoeaGastrointestinal disorders5/152/16
Pleural effusionRespiratory, thoracic and mediastinal disorders3/155/16
NauseaGastrointestinal disorders4/152/16
LeukocytosisBlood and lymphatic system disorders2/154/16
HypernatraemiaMetabolism and nutrition disorders3/154/16
MalnutritionMetabolism and nutrition disorders1/154/16
AtelectasisRespiratory, thoracic and mediastinal disorders0/154/16

Baseline characteristics

Age, Continuous
Age, Continuous(Years)Nivolumab (480 mg)Nivolumab (960 mg)Total
Mean56.6 ± 12.3058.4 ± 15.1657.5 ± 13.65
Sex: Female, Male
Sex: Female, Male(Participants)Nivolumab (480 mg)Nivolumab (960 mg)Total
Female4610
Male111021
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Nivolumab (480 mg)Nivolumab (960 mg)Total
Hispanic or Latino213
Not Hispanic or Latino131528
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Nivolumab (480 mg)Nivolumab (960 mg)Total
American Indian or Alaska Native000
Asian000
Native Hawaiian or Other Pacific Islander000
Black or African American246
White121123
More than one race000
Unknown or Not Reported112
08

Study locations

16 sites
  • Uc Davis Medical Center
    Sacramento, California 95817, United States
  • Univ. Of Colorado Health
    Colorado Springs, Colorado 80909, United States
  • Denver Health Medical Center
    Denver, Colorado 80204, United States
  • University Of Florida
    Gainesville, Florida 32610, United States
  • Pulmonary And Critical Care Of Atlanta
    Atlanta, Georgia 30303, United States
  • Osf Saint Francis Medical Center
    Peoria, Illinois 61637, United States
  • University Of Kentucky
    Lexington, Kentucky 40536, United States
  • Massachusetts General Hospital
    Boston, Massachusetts 02114, United States
  • Beth Israel Deaconess Medical Center (BIDMC)
    Boston, Massachusetts 02215, United States
  • Baystate Medical Center
    Springfield, Massachusetts 01199, United States
  • University of Michigan, Division of Acute Care Surgery
    Ann Arbor, Michigan 48109-5008, United States
  • Washington University School Of Medicine
    Saint Louis, Missouri 63110, United States
  • Duke University Medical Center
    Durham, North Carolina 27710, United States
  • The Ohio State University
    Columbus, Ohio 43210, United States
  • UPMC
    Pittsburgh, Pennsylvania 15261-2500, United States
  • Harborview Medical Center
    Seattle, Washington 98104, United States
09

References and documents

Publications

  • 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. PubMed 31576433 ↗

Study documents

  • Statistical analysis plan · May 17, 2017
  • Study protocol · Mar 3, 2017

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Apr 23, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02960854
Lead sponsor
Bristol-Myers Squibb
Responsible party
Sponsor
First posted
Nov 10, 2016
Start date
Dec 7, 2016
Primary completion
Jan 5, 2018
Completion
Jan 5, 2018
Results posted
Apr 4, 2019
Last update
Apr 23, 2019

Study contacts

Bristol-Myers Squibb
study director · Bristol-Myers Squibb

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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