Study of the Clinical Effectiveness of a Human Monoclonal Antibody to C. Difficile Toxin A and Toxin B in Patients With Clostridium Difficile Associated Disease

January 21, 2021 updated by: MassBiologics

A Phase II Randomized, Double-Blind, Placebo-Controlled Study of the Clinical Effectiveness of a Human Monoclonal Antibody to Clostridium Difficile Toxin A (GS-CDA1) and a Human Monoclonal Antibody to Clostridium Difficile Toxin B (MDX-1388) in Patients Being Treated for Clostridium Difficile Associated Disease

Patients with Clostridium difficile associated disease who fulfill the eligibility criteria will be approached to participate. All study patients must receive standard of care treatment for Clostridium difficile associated disease. Enrolled patients will be randomized to receive a single intravenous solution of a human monoclonal antibody (huMab) to C. difficile toxin A (GS-CDA1) combined with a human monoclonal antibody to C. difficile toxin B (MDX-1388) or 0.9% sodium chloride as placebo in a 1:1 treatment allocation. Patients will be evaluated for safety and clinical outcomes through day 84 +/- 10 days. Occurrence of adverse events, use of concomitant medications, and stool output will be assessed at scheduled phone contacts and study visits. Some patients enrolled will have a subsequent visit on day 168 ± 14 days.

Study Overview

Status

Status

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

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.

Detailed Description

This study is a phase II, randomized, double-blind, placebo-controlled study in patients diagnosed with Clostridium difficile associated disease. Patients with Clostridium difficile associated disease will be identified either from stool test results or by physician referral, and those who fulfill the eligibility criteria will be approached to participate. All study patients must receive standard of care treatment for Clostridium difficile associated disease. Enrolled patients will be randomized to receive a single intravenous solution of a human monoclonal antibody to C. difficile toxin A (GS-CDA1) combined with a human monoclonal antibody to C. difficile toxin B (MDX-1388) or 0.9% sodium chloride as placebo in a 1:1 treatment allocation. One hundred patients will be enrolled in the combination monoclonal antibody treated arm and 100 patients will be enrolled in the placebo arm. Patients will be evaluated through day 84 ± 10 days after receipt of study infusion for safety and clinical outcomes. Blood samples for safety analyses, anti-toxin A and anti-toxin B antibody measurements and human anti-human antibody (HAHA) titers will be collected at scheduled times. Study visits will occur on days 3 ± 1, 10 ± 2, 28 ± 3, 56 ± 7 and on day 84 ± 10 days. Occurrence of adverse events, use of concomitant medications, and record of stool output will be assessed at scheduled phone contacts and study visits. The first 20 patients enrolled will have a subsequent visit on day 168 ± 14 days for an additional blood collection for HAHA analysis.

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.
200

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 2

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

  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 2T9
        • University of Calgary Foothills Medical Center
    • British Columbia
      • Victoria, British Columbia, Canada, V8R 1J8
        • Vancouver Island Health Research Centre
    • Manitoba
      • Winnepeg, Manitoba, Canada, R3A 1R9
        • Health Sciences Centre, University of Manitoba
    • Ontario
      • Kingston, Ontario, Canada, K7L 2V7
        • Kingston General Hospital
      • WIndsor, Ontario, Canada, N8W 1L9
        • Windsor Regional Hospital
    • Quebec
      • Chicoutimi, Quebec, Canada, G7H 5H6
        • Centre de Sante et Services Sociaux de Chicoutimi
      • Trois-Rivieres, Quebec, Canada, G8Z 3R9
        • Centre hospitalier regional de Trois-Rivieres
  • United States
    • California
      • Los Angeles, California, United States, 90033
        • LAC/USC Medical Center
      • Los Angeles, California, United States, 90095
        • UCLA CURE Digestive Diseases Center
      • Oakland, California, United States, 94612
        • Kaiser Permanente Vaccine Study Center
    • Delaware
      • Newark, Delaware, United States, 19718
        • Christiana Care Health Systems
    • Florida
      • Tampa, Florida, United States, 33613
        • Dr. Kiran C. Patel Research Institute
    • Idaho
      • Idaho Falls, Idaho, United States, 83404
        • Idaho Falls Infectious Diseases, PLLC
    • Indiana
      • Anderson, Indiana, United States, 46016
        • Central Indiana Gastroenterology Group
    • Iowa
      • Des Moines, Iowa, United States, 50325
        • Chest, Infectious Diseases and Critical Care Assoc., PC
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • University of Kentucky Medical Center
    • Michigan
      • West Bloomfield, Michigan, United States, 48322
        • Henry Ford Health System
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
    • Missouri
      • Kansas City, Missouri, United States, 64111
        • Saint Luke's Hospital of Kansas City
    • Montana
      • Butte, Montana, United States, 59701
        • Saint James Healthcare
    • New Jersey
      • Neptune, New Jersey, United States, 07754
        • Jersey Shore University Medical Center
    • New York
      • New York, New York, United States, 10029
        • Mount Sinai Hospital
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27103
        • All-Trials Clinical Research, LLC
    • Ohio
      • Akron, Ohio, United States, 44304
        • Summa Health System
      • Columbus, Ohio, United States, 43214
        • Remington-Davis Clinical Research
    • South Dakota
      • Rapid City, South Dakota, United States, 57701
        • Rapid City Regional Hospital
    • Texas
      • Houston, Texas, United States, 77030
        • St. Lukes Episcopal Hospital
      • Temple, Texas, United States, 76508
        • Scott and White Memorial Hospital
    • Washington
      • Tacoma, Washington, United States, 98405
        • MultiCare Health System Research Services

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

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Patient > 18 years of age with diarrhea associated with a positive stool test for C. difficile toxin(s). Patients may be diagnosed with C. difficile by hospital/clinic/reference microbiology laboratory test or by a rapid diagnostic test performed by the study staff and positive test result must be within 14 days of enrollment.
  2. Patient must receive standard of care treatment for C. difficile associated disease. Standard of care treatment should include either metronidazole by mouth or intravenously or vancomycin by mouth.
  3. Patient or legal representative must have read, understood, and provided written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization after the nature of the study has been fully explained.

Exclusion Criteria:

  1. History of chronic diarrheal illness such as ulcerative colitis or Crohn's disease.
  2. Score of 4 on modified Horn's index
  3. Severe C. difficile colitis with planned surgery in less than 24 hours.
  4. Positive pregnancy test within 24 hours of study infusion or an unwillingness to undergo pregnancy testing in females of child-bearing potential. Females capable of child-bearing must agree not to become pregnant from the time of study enrollment until at least 3 months after completion of study infusion. If a woman is sexually active and has no history of hysterectomy or tubal ligation, she must agree to use hormonal or barrier birth control with spermicidal gel.
  5. Breastfeeding.
  6. Receipt of other investigational study agent within previous 30 days.
  7. Any other condition that in the opinion of the investigator would jeopardize the safety or rights of the patient participating in the study or make it unlikely the patient could complete the study.

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: GS-CDA1/MDX-1388
Biological: GS-CDA1/MDX-1388 One Intravenous dose
Biological: GS-CDA1/MDX-1388
One Intravenous dose
Placebo Comparator: Placebo
Biological: normal saline (0.9% sodium chloride) One Intravenous dose
Biological: normal saline
One Intravenous dose

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
Number of Participants With Recurrence of Clostridium Difficile Associated Disease (CDAD)
Time Frame: Day 0 to Day 84
Determine if the addition of C. difficile toxin A and toxin B human monoclonal anti-toxin antibodies to standard of care treatment reduces the number of subjects with recurrent CDAD compared to standard of care and placebo. Standard of care treatment is defined as receipt of either metronidazole by mouth or parenterally or receipt of vancomycin by mouth with a standard duration of treatment defined as 10 - 14 days (+ 2 days)). Recurrence of CDAD is defined as the development of a new episode of C. difficile disease associated with a positive C. difficile stool toxin(s) test after the resolution of prior episode and after discontinuation of SOC treatment.
Day 0 to Day 84

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
Safety and Tolerability of Study Treatment by the Number of Adverse Events Reported
Time Frame: Day 0 to Day 84
Safety and tolerability of a C. difficile toxin A human monoclonal antibody combined with a human monoclonal antibody to C. difficile toxin B in patients receiving standard of care treatment for C. difficile associated disease (CDAD) compared to those patients receiving standard of care and placebo reporting system organ class (SOC) MedDRA V.9.0
Day 0 to Day 84
Time to Resolution of Initial CDAD Episode
Time Frame: Day 0 to Day 84
Determine if the addition of a C. difficile toxin A human monoclonal antibody combined with C. difficile toxin B human monoclonal antibody to standard of care treatment reduces the time to resolution of diarrhea in patients with CDAD compared to those patients receiving standard of care and placebo. Resolution of CDAD is defined as the cessation of diarrhea for at least two consecutive days.
Day 0 to Day 84
Number of Patients With Standard of Care Treatment Failure
Time Frame: Day 0 to Day 84
Determine if the addition of a C. difficile toxin A human monoclonal antibody combined with C. difficile toxin B human monoclonal antibody to standard of care treatment reduces the number of patients who experience standard of care treatment failure compared to those patients receiving standard of care and placebo. Standard of care treatment failure is defined as (i) recurrence of diarrhea (after it had initially resolved) while on SOC treatment during the first 14 days, or (ii) change in SOC treatment (i.e., antibiotics given), or (iii) diarrhea episode lasting ≥14 days while on SOC treatment.
Day 0 to Day 84
Number of Patients With Severe Initial C. Difficile Disease
Time Frame: Day 0 to Day 84
Determine if the addition of a C. difficile toxin A human monoclonal antibody combined with C. difficile toxin B human monoclonal antibody to standard of care treatment reduces the number of patients with severe C. difficile disease compared to those patients receiving standard of care and placebo. Severe initial disease is defined as ≥ 5 unformed stools/day for 2 consecutive days from day 1 to the end of the initial episode of diarrhea and discontinuation of SOC.
Day 0 to Day 84
Antibody Concentrations to Toxin A and to Toxin B Between Treatment Groups
Time Frame: Day 0 to Day 84
Antibody concentrations to Toxin A and to Toxin B in those patients receiving C. difficile toxin A human monoclonal antibody combined with C. difficile toxin B human monoclonal antibody and standard of care treatment to those patients receiving standard of care and placebo
Day 0 to Day 84

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.
MassBiologics

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Medarex

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Roger Baxter, MD, Kaiser Permanente
  • Principal Investigator: Herbert DuPont, MD, St. Lukes Episcopal Hospital, Houston, TX
  • Principal Investigator: Joseph White, MD, Scott and White Memorial Hospital, Temple, TX
  • Principal Investigator: David Chen, MD, MultiCare Health System Research Services, Tacoma, WA
  • Principal Investigator: Jorge Reyno, MD, Rapid City Regional Hospital, Rapid City, SD
  • Principal Investigator: Henry S. Sacks, MD, PhD, Mount Sinai Hospital, New York, NY
  • Principal Investigator: Charles N. Bernstein, MD, University of Manitoba, Health Sciences Centre, Winnepeg, Manitoba, Canada
  • Principal Investigator: Michael J. Tan, MD, Summa Health Systems, Akron, Ohio
  • Principal Investigator: Michael C. Meadors, MD, All-Trials Clinical Research, LLC, Winston-Salem, NC
  • Principal Investigator: Ian M. Baird, MD, Remington-Davis Clinical Research
  • Principal Investigator: Andre Poirier, MD, MSc, Centre hospitalier regional de Trois-Rivieres
  • Principal Investigator: Martha I. Buitrago, MD, Idaho Falls Infectious Diseases, PLLC
  • Principal Investigator: Thomas Kovacs, MD, UCLA CURE Digestive Diseases Research Center
  • Principal Investigator: Alfred Bacon, MD, Christiana Care Health Systems
  • Principal Investigator: Kathleen Casey, MD, Jersey Shore University Medical Center
  • Principal Investigator: C. Douglas Cochran, MD, Saint Luke's Hospital of Kansas City
  • Principal Investigator: Donald Daly, MD, Vancouver Island Health Research Centre
  • Principal Investigator: Anil Dhar, MBBS, Windsor Regional Hospital
  • Principal Investigator: Gerald Evans, MD, Queen's University
  • Principal Investigator: Thomas Louie, MD, University of Calgary Foothills Medical Center
  • Principal Investigator: Thomas Nowak, MD, Central Indiana Gastroenterology Group
  • Principal Investigator: Jose Prieto, MD, Dr. Kiran C. Patel Research Institute
  • Principal Investigator: Daniel Schroeder, MD, Chest, Infectious Diseases and Critical Care Assoc., PC
  • Principal Investigator: Ann Silverman, MD, Henry Ford Health System
  • Principal Investigator: John Pullman, MD, Mercury Street Medical Group
  • Principal Investigator: Rodney J Mason, MD, LAC+USC Medical Center
  • Principal Investigator: Doria Grimard, MD, Centre De Sante Et De Services Sociaux De Chicoutimi
  • Principal Investigator: Darrell Pardi, MD, Mayo Clinic

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

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.
July 20, 2006

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.
June 25, 2008

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.
June 25, 2008

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).
July 7, 2006

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.
July 7, 2006

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.
July 10, 2006

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.
February 9, 2021

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.
January 21, 2021

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.
January 1, 2021

More Information

Terms related to this study

Keywords

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.
  • CA-GCDX-06-02

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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