Safety, Pharmacokinetics and Pharmacodynamics of BMS-936559 in Severe Sepsis

September 14, 2017 updated by: Bristol-Myers Squibb

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
35

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Sacramento, California, United States, 95817
        • UC Davis Medical Center
    • Colorado
      • Denver, Colorado, United States, 80204
        • Local Institution
    • Florida
      • Gainesville, Florida, United States, 32610
        • University of Florida
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University
    • Illinois
      • Peoria, Illinois, United States, 61637
        • OSF Saint Francis Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
      • Springfield, Massachusetts, United States, 01199
        • Baystate Medical Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48109-5033
        • University of Michigan, Division of Acute Care Surgery
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • Ohio
      • Columbus, Ohio, United States, 43210
        • The Ohio State University
      • Toledo, Ohio, United States, 43603
        • St. Vincent's Medical Center
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15261-2500
        • UPMC
    • Washington
      • Seattle, Washington, United States, 98104
        • Local Institution

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: BMS-936559
BMS-936559 Intravenous infusion on specified days
Biological: BMS-936559
Other: Placebo
Placebo on specified days
Other: Placebo

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
Approximately 3 months
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
Approximately 3 months
Part 2: All-cause mortality within 90 days of study drug administration
Time Frame: Approximately 3 months
Approximately 3 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Maximum observed serum concentration (Cmax) of BMS-936559
Time Frame: Approximately 3 months
Approximately 3 months
Time of maximum observed serum concentration (Tmax) of BMS-936559
Time Frame: Approximately 3 months
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
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
Approximately 3 months
Total Body Clearance (CLT) of BMS-936559
Time Frame: Approximately 3 months
Approximately 3 months
Volume of distribution at steady state (Vss) of BMS-936559
Time Frame: Approximately 3 months
Approximately 3 months
Terminal serum half-life (T-HALF) of BMS-936559
Time Frame: Approximately 3 months
Approximately 3 months
Receptor occupancy based on PD-L1 receptor occupancy levels
Time Frame: Approximately 3 months
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
Approximately 3 months
Immune system function based on absolute lymphocyte counts at planned sampling timepoints
Time Frame: Approximately 3 months
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
Approximately 3 months
Organ dysfunction measured by organ support-free days (OSFDs)
Time Frame: Approximately 3 months
OSFD is defined as the last period of organ support-free duration during the index hospitalization stay prior to discharge.
Approximately 3 months
Organ dysfunction measured by proportion of OSFDs during index hospitalization
Time Frame: Approximately 3 months
OSFD is defined as the last period of organ support-free duration during the index hospitalization stay prior to discharge.
Approximately 3 months
Duration of mechanical ventilation, vasopressor use, and/or dialysis use separately during the index hospitalization
Time Frame: Approximately 3 months
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
Approximately 3 months
All-cause mortality at 28 days, 90 days, and 1 year after study drug administration
Time Frame: 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.
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
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
Approximately 3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Bristol-Myers Squibb

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 2, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 15, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 15, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 13, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 14, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 15, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 15, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 14, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • AI471-049

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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