Severe SepsisPhase 1NCT02576457
Safety, Pharmacokinetics and Pharmacodynamics of BMS-936559 in Severe Sepsis
A Phase 1 study testing BMS-936559 in people with Severe Sepsis and Septic Shock, run by Bristol-Myers Squibb at 13 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Severe Sepsis, Septic Shock
- What is being tested?
- BMS-936559
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 35 participants
- Where
- 13 sitesUnited States
- Study dates
- 2 Dec 2015to 15 Mar 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Severe sepsis or septic shock for at least 24 hours
- Documented or suspected infection
- Sepsis-induced immunosuppression
- Men and women ≥ 18 years old
Who cannot join
- 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)
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
United States13 sites
University of Michigan, Division of Acute Care Surgery
Ann Arbor, Michigan, 48109-5033
Emory University
Atlanta, Georgia, 30322
Massachusetts General Hospital
Boston, Massachusetts, 02114
The Ohio State University
Columbus, Ohio, 43210
Local Institution
Denver, Colorado, 80204
University Of Florida
Gainesville, Florida, 32610
Osf Saint Francis Medical Center
Peoria, Illinois, 61637
UPMC
Pittsburgh, Pennsylvania, 15261-2500
Uc Davis Medical Center
Sacramento, California, 95817
Local Institution
Seattle, Washington, 98104
Baystate Medical Center
Springfield, Massachusetts, 01199
Washington University School Of Medicine
St Louis, Missouri, 63110
St. Vincent'S Medical Center
Toledo, Ohio, 43603
About this study
Official title: A Phase 1b/2a, Randomized, Double-Blinded, Placebo-Controlled, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BMS-936559 in Subjects With Severe Sepsis
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.
- Conditions
- Severe Sepsis, Septic Shock
- Being tested
- BMS-936559, Placebo
- Medical subject headings
- Sepsis, Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BMS-936559Biological
PlaceboOther
| Study group | Role | What they receive |
|---|---|---|
| BMS-936559 | Experimental | BMS-936559 Intravenous infusion on specified days Receives: Biological: BMS-936559 |
| Placebo | Other | Placebo on specified days Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
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
Measured: Approximately 3 months
Part 1: Tolerability of BMS-936559 in subjects with severe sepsis
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
Measured: Approximately 3 months
Part 2: All-cause mortality within 90 days of study drug administration
Measured: Approximately 3 months
Secondary outcomes (18)
Maximum observed serum concentration (Cmax) of BMS-936559
Measured: Approximately 3 months
Time of maximum observed serum concentration (Tmax) of BMS-936559
Measured: 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
Measured: Approximately 3 months
Area under the serum concentration-time curve from time zero extrapolated to infinite time (AUC(INF)) of BMS-936559
Measured: Approximately 3 months
Total Body Clearance (CLT) of BMS-936559
Measured: Approximately 3 months
Volume of distribution at steady state (Vss) of BMS-936559
Measured: Approximately 3 months
Terminal serum half-life (T-HALF) of BMS-936559
Measured: Approximately 3 months
Receptor occupancy based on PD-L1 receptor occupancy levels
Measured: Approximately 3 months
Immune system function based on baseline and post-dosing assessments of mHLA-DR expression on monocytes at planned sampling timepoints
Measured: Approximately 3 months
Immune system function based on absolute lymphocyte counts at planned sampling timepoints
Measured: Approximately 3 months
Immune system function based on lipopolysaccharide (LPS)-induced whole blood TNFalpha production levels at planned sampling timepoints
Measured: Approximately 3 months
Organ dysfunction measured by organ support-free days (OSFDs)
OSFD is defined as the last period of organ support-free duration during the index hospitalization stay prior to discharge.
Measured: Approximately 3 months
Organ dysfunction measured by proportion of OSFDs during index hospitalization
OSFD is defined as the last period of organ support-free duration during the index hospitalization stay prior to discharge.
Measured: Approximately 3 months
Duration of mechanical ventilation, vasopressor use, and/or dialysis use separately during the index hospitalization
Measured: Approximately 3 months
Incidence of secondary infections (as adjudicated by a clinical committee) up to 90 days post administration of BMS-936559
Measured: Approximately 3 months
All-cause mortality at 28 days, 90 days, and 1 year after study drug administration
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.
Measured: Approximately 3 months
Immunogenicity measured by number of subjects having detectable anti-drug antibodies (ADA) at baseline and following administration of BMS-936559.
Measured: Approximately 3 months
Immunogenicity measured by percentage of subjects having detectable anti-drug antibodies (ADA) at baseline and following administration of BMS-936559.
Measured: Approximately 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2015 (estimated)
- Study start2 Dec 2015
- Primary completion15 Mar 2017
- Study completion15 Mar 2017
Why it stopped: Business Objectives Have Changed
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 35 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
- NCT02576457
- Sponsor's protocol ID
- AI471-049
- Status last verified
- Sep 2017
- First submitted
- 13 Oct 2015
- Last updated
- 15 Sep 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Hotchkiss RS, Colston E, Yende S, Angus DC, Moldawer LL, Crouser ED, Martin GS, Coopersmith CM, Brakenridge S, Mayr FB, Park PK, Ye J, Catlett IM, Girgis IG, Grasela DM. Immune Checkpoint Inhibition in Sepsis: A Phase 1b Randomized, Placebo-Controlled, Single Ascending Dose Study of Antiprogrammed Cell Death-Ligand 1 Antibody (BMS-936559). Crit Care Med. 2019 May;47(5):632-642. doi: 10.1097/CCM.0000000000003685.
PubMed 30747773
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b/2a, Randomized, Double-Blinded, Placebo-Controlled, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BMS-936559 in Subjects With Severe Sepsis
- ClinicalTrials.gov ID
- NCT02576457
- Acronym / sponsor ID
- AI471-049
- Conditions
- Severe Sepsis, Septic Shock
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Business Objectives Have Changed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Study start
- 2 Dec 2015 (actual)
- Primary completion
- 15 Mar 2017 (actual)
- Study completion
- 15 Mar 2017 (actual)
- First posted
- 15 Oct 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| BMS-936559 | Experimental | Biological: BMS-936559BMS-936559 Intravenous infusion on specified days |
| Placebo | Other | Other: PlaceboPlacebo on specified days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Severe sepsis or septic shock for at least 24 hours
- Documented or suspected infection
- Sepsis-induced immunosuppression
- Men and women ≥ 18 years old
Key exclusion criteria (6 listed)
- 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
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 |
|---|---|---|
| BMS-936559 | Biological | BMS-936559 |
| Placebo | Other | Placebo |
Primary outcome
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
Time frame: 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
Time frame: 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
Time frame: Approximately 3 months
18 secondary outcomes
Maximum observed serum concentration (Cmax) of BMS-936559
Time frame: Approximately 3 months
Time of maximum observed serum concentration (Tmax) of BMS-936559
Time frame: 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
Time frame: Approximately 3 months
Area under the serum concentration-time curve from time zero extrapolated to infinite time (AUC(INF)) of BMS-936559
Time frame: Approximately 3 months
Total Body Clearance (CLT) of BMS-936559
Time frame: Approximately 3 months
Volume of distribution at steady state (Vss) of BMS-936559
Time frame: Approximately 3 months
Terminal serum half-life (T-HALF) of BMS-936559
Time frame: Approximately 3 months
Receptor occupancy based on PD-L1 receptor occupancy levels
Time frame: Approximately 3 months
Immune system function based on baseline and post-dosing assessments of mHLA-DR expression on monocytes at planned sampling timepoints
Time frame: Approximately 3 months
Immune system function based on absolute lymphocyte counts at planned sampling timepoints
Time frame: Approximately 3 months
Immune system function based on lipopolysaccharide (LPS)-induced whole blood TNFalpha production levels at planned sampling timepoints
Time frame: Approximately 3 months
Organ dysfunction measured by organ support-free days (OSFDs)
Time frame: Approximately 3 months
Organ dysfunction measured by proportion of OSFDs during index hospitalization
Time frame: Approximately 3 months
Duration of mechanical ventilation, vasopressor use, and/or dialysis use separately during the index hospitalization
Time frame: Approximately 3 months
Incidence of secondary infections (as adjudicated by a clinical committee) up to 90 days post administration of BMS-936559
Time frame: Approximately 3 months
All-cause mortality at 28 days, 90 days, and 1 year after study drug administration
Time frame: Approximately 3 months
Immunogenicity measured by number of subjects having detectable anti-drug antibodies (ADA) at baseline and following administration of BMS-936559.
Time frame: Approximately 3 months
Immunogenicity measured by percentage of subjects having detectable anti-drug antibodies (ADA) at baseline and following administration of BMS-936559.
Time frame: Approximately 3 months
Results and safety
The study was stopped early (reason given: Business Objectives Have Changed). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2017.
- Derived from this study: PubMed 30747773Hotchkiss RS, Colston E, Yende S, Angus DC, Moldawer LL, Crouser ED, Martin GS, Coopersmith CM, Brakenridge S, Mayr FB, Park PK, Ye J, Catlett IM, Girgis IG, Grasela DM. Immune Checkpoint Inhibition in Sepsis: A Phase 1b Randomized, Placebo-Controlled, Single Ascending Dose Study of Antiprogrammed Cell Death-Ligand 1 Antibody (BMS-936559). Crit Care Med. 2019 May;47(5):632-642. doi: 10.1097/CCM.0000000000003685.
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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
13 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 BMS-936559 in people with Severe Sepsis and Septic Shock, run by Bristol-Myers Squibb at 13 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 4 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: stopped early, as of the sponsor's last update on 15 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 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?
The study was stopped early (reason given: Business Objectives Have Changed). Results are not available in the source record.
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?
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 (time frame: Approximately 3 months). The study lists 3 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 NCT02576457, 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 15 Sep 2017.