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

This study has been completed.
Sponsor:
Collaborator:
Medarex
Information provided by:
University of Massachusetts, Worcester
ClinicalTrials.gov Identifier:
NCT00350298
First received: July 7, 2006
Last updated: October 26, 2010
Last verified: October 2010

July 7, 2006
October 26, 2010
July 2006
July 2008   (final data collection date for primary outcome measure)
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 ] [ Designated as safety issue: No ]
  • with standard of care treatment.
  • To describe the course of resolution of illness in the standard of care plus
  • placebo population and estimate by a number of exploratory analyses the presence
  • and magnitude of a favorable treatment effect provided by the addition of a
  • combination of human monoclonal antibodies to C. difficile toxin A and toxin B
Complete list of historical versions of study NCT00350298 on ClinicalTrials.gov Archive Site
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • To evaluate safety and tolerability 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) administered to patients receiving standard of care
  • treatment for C. difficile associated disease compared to patients receiving
  • standard of care and placebo.
  • To determine if the addition of a combination of human monoclonal antibodies to
  • C. difficile toxin A and C. difficile toxin B with standard of care treatment
  • reduces the proportion of patients with recurrent Clostridium difficile
  • associated disease after completion of standard of care treatment compared to
  • those patients receiving standard of care and placebo.
Not Provided
Not Provided
 
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
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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Clostridium Infections
  • Biological: GS-CDA1
    one dose IV
  • Biological: MDX-1388
    one dose IV
  • Biological: normal saline
    200ml IV once
  • Active Comparator: 1
    GS-CDA1 and MDX-1388
    Interventions:
    • Biological: GS-CDA1
    • Biological: MDX-1388
  • Placebo Comparator: 2
    normal saline (0.9% sodium chloride)
    Intervention: Biological: normal saline
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
200
October 2008
July 2008   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT00350298
CA-GCDX-06-02
Yes
Deborah Molrine, Massachusetts Biologic Laboratories
University of Massachusetts, Worcester
Medarex
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University of Massachusetts, Worcester
October 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP