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

NCT00350298 | Completed Phase 2 Results DMC

• 1 other identifier: CA-GCDX-06-02
• Study Type: interventional
• Target: 200
• Locations: 2 countries
• Sites: 29

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.

Conditions

Clostridium Infections

Keywords

Monoclonal antibody,; Clostridium difficile Associated Diarrhea

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Safety and Tolerability of Study Treatment by the Number of Adverse Events Reported

  Day 0 to Day 84

• Time to Resolution of Initial CDAD Episode

  Day 0 to Day 84

• Number of Patients With Standard of Care Treatment Failure

  Day 0 to Day 84

• Number of Patients With Severe Initial C. Difficile Disease

  Day 0 to Day 84

• Antibody Concentrations to Toxin A and to Toxin B Between Treatment Groups

  Day 0 to Day 84

Study Arms (2)

GS-CDA1/MDX-1388

EXPERIMENTAL

Biological: GS-CDA1/MDX-1388 One Intravenous dose

Biological: GS-CDA1/MDX-1388

Placebo

PLACEBO COMPARATOR

Biological: normal saline (0.9% sodium chloride) One Intravenous dose

Biological: normal saline

Interventions

GS-CDA1/MDX-1388 BIOLOGICAL

One Intravenous dose

GS-CDA1/MDX-1388

normal saline BIOLOGICAL

One Intravenous dose

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• 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.

You may not qualify if:

• History of chronic diarrheal illness such as ulcerative colitis or Crohn's disease.
• Score of 4 on modified Horn's index
• Severe C. difficile colitis with planned surgery in less than 24 hours.
• 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.
• Breastfeeding.
• Receipt of other investigational study agent within previous 30 days.
• 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.

Sponsors & Collaborators

• MassBiologics: lead
• Medarex: collaborator

Study Sites (29)

LAC/USC Medical Center

Los Angeles, California, 90033, United States

Location

UCLA CURE Digestive Diseases Center

Los Angeles, California, 90095, United States

Location

Kaiser Permanente Vaccine Study Center

Oakland, California, 94612, United States

Location

Christiana Care Health Systems

Newark, Delaware, 19718, United States

Location

Dr. Kiran C. Patel Research Institute

Tampa, Florida, 33613, United States

Location

Idaho Falls Infectious Diseases, PLLC

Idaho Falls, Idaho, 83404, United States

Location

Central Indiana Gastroenterology Group

Anderson, Indiana, 46016, United States

Location

Chest, Infectious Diseases and Critical Care Assoc., PC

Des Moines, Iowa, 50325, United States

Location

University of Kentucky Medical Center

Lexington, Kentucky, 40536, United States

Location

Henry Ford Health System

West Bloomfield, Michigan, 48322, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Saint Luke's Hospital of Kansas City

Kansas City, Missouri, 64111, United States

Location

Saint James Healthcare

Butte, Montana, 59701, United States

Location

Jersey Shore University Medical Center

Neptune City, New Jersey, 07754, United States

Location

Mount Sinai Hospital

New York, New York, 10029, United States

Location

All-Trials Clinical Research, LLC

Winston-Salem, North Carolina, 27103, United States

Location

Summa Health System

Akron, Ohio, 44304, United States

Location

Remington-Davis Clinical Research

Columbus, Ohio, 43214, United States

Location

Rapid City Regional Hospital

Rapid City, South Dakota, 57701, United States

Location

St. Lukes Episcopal Hospital

Houston, Texas, 77030, United States

Location

Scott and White Memorial Hospital

Temple, Texas, 76508, United States

Location

MultiCare Health System Research Services

Tacoma, Washington, 98405, United States

Location

University of Calgary Foothills Medical Center

Calgary, Alberta, T2N 2T9, Canada

Location

Vancouver Island Health Research Centre

Victoria, British Columbia, V8R 1J8, Canada

Location

Health Sciences Centre, University of Manitoba

Winnepeg, Manitoba, R3A 1R9, Canada

Location

Kingston General Hospital

Kingston, Ontario, K7L 2V7, Canada

Location

Windsor Regional Hospital

Windsor, Ontario, N8W 1L9, Canada

Location

Centre de Sante et Services Sociaux de Chicoutimi

Chicoutimi, Quebec, G7H 5H6, Canada

Location

Centre Hospitalier Regional de Trois-Rivieres

Trois-Rivières, Quebec, G8Z 3R9, Canada

Location

Related Publications (3)

• Montgomery DL, Matthews RP, Yee KL, Tobias LM, Dorr MB, Wrishko RE. Assessment of Bezlotoxumab Immunogenicity. Clin Pharmacol Drug Dev. 2020 Apr;9(3):330-340. doi: 10.1002/cpdd.729. Epub 2019 Aug 14.

  PMID: 31411386 DERIVED

• 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.

  PMID: 27365387 DERIVED

• 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.

  PMID: 20089970 DERIVED

MeSH Terms

Conditions

Clostridium Infections

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Director of Clinical Affairs
• Organization: MassBiologics

MBLClinicalDirector@umassmed.edu

617-474-3000

Study Officials

• 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

  St. Luke's Hospital, Kansas City, Missouri

  PRINCIPAL INVESTIGATOR

• Donald Daly, MD

  Vancouver Island Health Research Centre

  PRINCIPAL INVESTIGATOR

• Anil Dhar, MBBS

  Windsor Regional Hospital

  PRINCIPAL INVESTIGATOR

• Gerald Evans, MD

  Kingston Health Sciences Centre

  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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2006
• First Posted: July 10, 2006
• Study Start: July 20, 2006
• Primary Completion: June 25, 2008
• Study Completion: June 25, 2008
• Last Updated: February 9, 2021
• Results First Posted: February 9, 2021

Record last verified: 2021-01

Locations

CA (7); US (22)