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

Study Description

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Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Clostridium Infections	Biological: GS-CDA1; Biological: MDX-1388; Biological: normal saline	Phase 2

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 Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	200 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	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
Study Start Date :	July 2006
Actual Primary Completion Date :	July 2008
Actual Study Completion Date :	October 2008

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Active Comparator: 1; GS-CDA1 and MDX-1388	Biological: GS-CDA1; one dose IV Biological: MDX-1388; one dose IV
Placebo Comparator: 2; normal saline (0.9% sodium chloride)	Biological: normal saline; 200ml IV once

Outcome Measures

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. Determine if the addition of C. difficile toxin A and toxin B human monoclonal anti-toxin antibodies to standard of care treatment reduces the proportion of subjects with recurrent CDAD compared to standard of care and placebo. [ Time Frame: 3 Months Study Period ]

Secondary Outcome Measures :

1. Evaluate safety and tolerability of human monoclonal anti-toxin antibodies in patients receiving standard of care treatment for CDAD compared to standard of care and placebo. [ Time Frame: 3 Months Study Period ]
2. Determine if the addition of human monoclonal antibodies to C. difficile toxin A and toxin B and standard of care treatment; reduces the time to resolution of diarrhea in patients with CDAD compared to standard of care and placebo. [ Time Frame: 3 Months Study Period ]
3. Determine if the addition of human monoclonal antibodies to C. difficile toxin A and toxin B and standard of care treatment; reduces the proportion of patients who experience standard of care treatment failure compared to standard of care and placebo. [ Time Frame: 3 Months Study Period ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

  Show 29 Study Locations

Sponsors and Collaborators

University of Massachusetts, Worcester

Medarex

Investigators

Principal Investigator:	Roger Baxter, MD	Kaiser Permanente Vaccine Study Center
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	Kingston General Hospital
Principal Investigator:	Richard Greenberg, MD	University of Kentucky
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

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Gupta SB, Mehta V, Dubberke ER, Zhao X, Dorr MB, Guris D, Molrine D, Leney M, Miller M, Dupin M, Mast TC. Antibodies to Toxin B Are Protective Against Clostridium difficile Infection Recurrence. Clin Infect Dis. 2016 Sep 15;63(6):730-734. doi: 10.1093/cid/ciw364. Epub 2016 Jun 30.

Lowy I, Molrine DC, Leav BA, Blair BM, Baxter R, Gerding DN, Nichol G, Thomas WD Jr, Leney M, Sloan S, Hay CA, Ambrosino DM. Treatment with monoclonal antibodies against Clostridium difficile toxins. N Engl J Med. 2010 Jan 21;362(3):197-205. doi: 10.1056/NEJMoa0907635.

Responsible Party:	Deborah Molrine, Massachusetts Biologic Laboratories
ClinicalTrials.gov Identifier:	NCT00350298 History of Changes
Other Study ID Numbers:	CA-GCDX-06-02
First Posted:	July 10, 2006
Last Update Posted:	November 1, 2010
Last Verified:	October 2010

Keywords provided by University of Massachusetts, Worcester:

Monoclonal antibody,; Clostridium difficile Associated Diarrhea

Additional relevant MeSH terms:

Clostridium Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Antibodies	Immunoglobulins; Antibodies, Monoclonal; Immunologic Factors; Physiological Effects of Drugs