Severe SepsisPhase 1NCT02960854
A Study of Nivolumab Safety and Pharmacokinetics in Patients With Severe Sepsis or Septic Shock.
A Phase 1 study testing Nivolumab in people with Severe Sepsis, run by Bristol-Myers Squibb at 16 sites in United States.
Trial summary
A study to evaluate the safety, tolerability and pharmacokinetics of Nivolumab in participants with severe sepsis or septic shock. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Severe Sepsis
- What is being tested?
- Nivolumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 16 sitesUnited States
- Study dates
- 7 Dec 2016to 5 Jan 2018
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
16 sites in 1 country.
16 sites in 1 country
United States16 sites
University of Michigan, Division of Acute Care Surgery
Ann Arbor, Michigan, 48109-5008
Pulmonary And Critical Care Of Atlanta
Atlanta, Georgia, 30303
Massachusetts General Hospital
Boston, Massachusetts, 02114
Beth Israel Deaconess Medical Center (BIDMC)
Boston, Massachusetts, 02215
Univ. Of Colorado Health
Colorado Springs, Colorado, 80909
The Ohio State University
Columbus, Ohio, 43210
Denver Health Medical Center
Denver, Colorado, 80204
Duke University Medical Center
Durham, North Carolina, 27710
University Of Florida
Gainesville, Florida, 32610
University Of Kentucky
Lexington, Kentucky, 40536
Osf Saint Francis Medical Center
Peoria, Illinois, 61637
UPMC
Pittsburgh, Pennsylvania, 15261-2500
Uc Davis Medical Center
Sacramento, California, 95817
Harborview Medical Center
Seattle, Washington, 98104
Baystate Medical Center
Springfield, Massachusetts, 01199
Washington University School Of Medicine
St Louis, Missouri, 63110
About this study
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.
A study to evaluate the safety, tolerability and pharmacokinetics of Nivolumab in participants with severe sepsis or septic shock.
- Conditions
- Severe Sepsis
- Being tested
- Nivolumab
- Medical subject headings
- Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabBiological
Also called BMS-936558
Specified dose on specified days
| Study group | Role | What they receive |
|---|---|---|
| Nivolumab 1 | Experimental | Dose 1 Receives: Biological: Nivolumab |
| Nivolumab 2 | Experimental | Dose 2 Receives: Biological: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Incidence Rates of Serious Adverse Events (SAEs), Adverse Events (AEs), Immune-mediated AEs, AEs Leading to Discontinuation, and Deaths
Measured: 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.
Measured: Screening up to 90 days (Discharge)
Peak Nivolumab Serum Concentration (Cmax)
Participants peak nivolumab serum concentration
Measured: Day 1 and subsequent days after, up to 90 days
Trough Nivolumab Serum Concentration (Cmin)
Participant trough nivolumab serum concentration
Measured: Day 1 and subsequent days after, up to 90 days
Average Nivolumab Serum Concentration (Cavg)
Participant average nivolumab serum concentration
Measured: Day 1 and subsequent days after, up to 90 days
Time of Maximum Observed Concentration (Tmax)
Participant observed time of maximum concentration
Measured: 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
Measured: Day 1 and subsequent days after, up to 90 days
Total Clearance (CLT)
Total clearance of serum concentration of nivolumab
Measured: Day 1 and subsequent days after, up to 90 days
Volume of Distribution (Vd)
Vlume of distribution of nivolumab serum concentration
Measured: Day 1 and subsequent days after, up to 90 days
Half-life (T1/2)
Half-Life of nivolumab derived from serum concentration
Measured: Day 1 and subsequent days after, up to 90 days
Secondary outcomes (3)
Receptor Occupancy
Receptor occupancy on T cells at baseline and after study treatment administration at planned sampling time points
Measured: Day 1 and up to day 90 (discharge)
Number of Participants With Detectable Anti-nivolumab Antibodies
Participant with positive anti-drug antibody detection
Measured: Baseline and subsequent days after, up to 90 days
Number of Participants With Any Detectable Anti-drug Antibodies
Measured: Baseline and subsequent days after, up to 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2016 (estimated)
- Study start7 Dec 2016
- Primary completion5 Jan 2018
- Study completion5 Jan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Severe SepsisStudies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02960854
- Sponsor's protocol ID
- CA209-923
- Status last verified
- Apr 2019
- First submitted
- 8 Nov 2016
- Last updated
- 23 Apr 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
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 at a glance
From the registry record, last updated by the sponsor on 23 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT02960854
- Acronym / sponsor ID
- CA209-923
- Conditions
- Severe Sepsis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Study start
- 7 Dec 2016 (actual)
- Primary completion
- 5 Jan 2018 (actual)
- Study completion
- 5 Jan 2018 (actual)
- First posted
- 10 Nov 2016 (estimated)
- Results
- Posted 4 Apr 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A study to evaluate the safety, tolerability and pharmacokinetics of Nivolumab in participants with severe sepsis or septic shock.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nivolumab 1 | Experimental | Biological: NivolumabDose 1 |
| Nivolumab 2 | Experimental | Biological: NivolumabDose 2 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NivolumabAlso: BMS-936558Specified dose on specified days | Biological | Nivolumab 1, Nivolumab 2 |
Primary outcome
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
Composite of Vital Signs and Electrocardiogram (ECG)
Time frame: Screening up to 90 days (Discharge)
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.
Peak Nivolumab Serum Concentration (Cmax)
Time frame: Day 1 and subsequent days after, up to 90 days
Participants peak nivolumab serum concentration
Trough Nivolumab Serum Concentration (Cmin)
Time frame: Day 1 and subsequent days after, up to 90 days
Participant trough nivolumab serum concentration
Average Nivolumab Serum Concentration (Cavg)
Time frame: Day 1 and subsequent days after, up to 90 days
Participant average nivolumab serum concentration
Time of Maximum Observed Concentration (Tmax)
Time frame: Day 1 and subsequent days after, up to 90 days
Participant observed time of maximum concentration
Area Under the Serum Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration [AUC(0-T)]
Time frame: 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
Total Clearance (CLT)
Time frame: Day 1 and subsequent days after, up to 90 days
Total clearance of serum concentration of nivolumab
Volume of Distribution (Vd)
Time frame: Day 1 and subsequent days after, up to 90 days
Vlume of distribution of nivolumab serum concentration
Half-life (T1/2)
Time frame: Day 1 and subsequent days after, up to 90 days
Half-Life of nivolumab derived from serum concentration
3 secondary outcomes
Receptor Occupancy
Time frame: Day 1 and up to day 90 (discharge)
Number of Participants With Detectable Anti-nivolumab Antibodies
Time frame: Baseline and subsequent days after, up to 90 days
Number of Participants With Any Detectable Anti-drug Antibodies
Time frame: Baseline and subsequent days after, up to 90 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31576433Hotchkiss 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
16 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Nivolumab in people with Severe Sepsis, run by Bristol-Myers Squibb at 16 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Apr 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02960854, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Apr 2019.