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

Clostridium Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00350298
• Other study ID #: CA-GCDX-06-02
• Status: Completed
• Phase: Phase 2
• Start date: July 20, 2006
• Est. completion date: June 25, 2008

Study information

• Verified date: January 2021
• Source: MassBiologics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: June 25, 2008
• Est. primary completion date: June 25, 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Clostridium Infections

Intervention

Biological:
• GS-CDA1/MDX-1388
One Intravenous dose
• normal saline
One Intravenous dose

Locations

Country	Name	City	State
Canada	University of Calgary Foothills Medical Center	Calgary	Alberta
Canada	Centre de Sante et Services Sociaux de Chicoutimi	Chicoutimi	Quebec
Canada	Kingston General Hospital	Kingston	Ontario
Canada	Centre Hospitalier Regional de Trois-Rivieres	Trois-Rivieres	Quebec
Canada	Vancouver Island Health Research Centre	Victoria	British Columbia
Canada	Windsor Regional Hospital	WIndsor	Ontario
Canada	Health Sciences Centre, University of Manitoba	Winnepeg	Manitoba
United States	Summa Health System	Akron	Ohio
United States	Central Indiana Gastroenterology Group	Anderson	Indiana
United States	Saint James Healthcare	Butte	Montana
United States	Remington-Davis Clinical Research	Columbus	Ohio
United States	Chest, Infectious Diseases and Critical Care Assoc., PC	Des Moines	Iowa
United States	St. Lukes Episcopal Hospital	Houston	Texas
United States	Idaho Falls Infectious Diseases, PLLC	Idaho Falls	Idaho
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	University of Kentucky Medical Center	Lexington	Kentucky
United States	LAC/USC Medical Center	Los Angeles	California
United States	UCLA CURE Digestive Diseases Center	Los Angeles	California
United States	Jersey Shore University Medical Center	Neptune	New Jersey
United States	Mount Sinai Hospital	New York	New York
United States	Christiana Care Health Systems	Newark	Delaware
United States	Kaiser Permanente Vaccine Study Center	Oakland	California
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Mayo Clinic	Rochester	Minnesota
United States	MultiCare Health System Research Services	Tacoma	Washington
United States	Dr. Kiran C. Patel Research Institute	Tampa	Florida
United States	Scott and White Memorial Hospital	Temple	Texas
United States	Henry Ford Health System	West Bloomfield	Michigan
United States	All-Trials Clinical Research, LLC	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
MassBiologics	Medarex

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Recurrence of Clostridium Difficile Associated Disease (CDAD)	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	Safety and Tolerability of Study Treatment by the Number of Adverse Events Reported	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
Secondary	Time to Resolution of Initial CDAD Episode	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
Secondary	Number of Patients With Standard of Care Treatment Failure	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
Secondary	Number of Patients With Severe Initial C. Difficile Disease	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
Secondary	Antibody Concentrations to Toxin A and to Toxin B Between Treatment Groups	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