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

NCT ID: NCT00350298

Last Updated: 2021-02-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-07-20
• Study Completion Date: 2008-06-25

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.

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.

Conditions

Clostridium Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

GS-CDA1/MDX-1388

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

Group Type: EXPERIMENTAL

GS-CDA1/MDX-1388

Intervention Type: BIOLOGICAL

One Intravenous dose

Placebo

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

Group Type: PLACEBO_COMPARATOR

normal saline

Intervention Type: BIOLOGICAL

One Intravenous dose

Interventions

GS-CDA1/MDX-1388

One Intravenous dose

Intervention Type: BIOLOGICAL

normal saline

One Intravenous dose

Intervention Type: BIOLOGICAL

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medarex

INDUSTRY

Sponsor Role: collaborator

MassBiologics

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Roger Baxter, MD

Role: PRINCIPAL_INVESTIGATOR

Kaiser Permanente

Herbert DuPont, MD

Role: PRINCIPAL_INVESTIGATOR

St. Lukes Episcopal Hospital, Houston, TX

Joseph White, MD

Role: PRINCIPAL_INVESTIGATOR

Scott and White Memorial Hospital, Temple, TX

David Chen, MD

Role: PRINCIPAL_INVESTIGATOR

MultiCare Health System Research Services, Tacoma, WA

Jorge Reyno, MD

Role: PRINCIPAL_INVESTIGATOR

Rapid City Regional Hospital, Rapid City, SD

Henry S. Sacks, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Mount Sinai Hospital, New York, NY

Charles N. Bernstein, MD

Role: PRINCIPAL_INVESTIGATOR

University of Manitoba, Health Sciences Centre, Winnepeg, Manitoba, Canada

Michael J. Tan, MD

Role: PRINCIPAL_INVESTIGATOR

Summa Health Systems, Akron, Ohio

Michael C. Meadors, MD

Role: PRINCIPAL_INVESTIGATOR

All-Trials Clinical Research, LLC, Winston-Salem, NC

Ian M. Baird, MD

Role: PRINCIPAL_INVESTIGATOR

Remington-Davis Clinical Research

Andre Poirier, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

Centre Hospitalier Regional de Trois-Rivieres

Martha I. Buitrago, MD

Role: PRINCIPAL_INVESTIGATOR

Idaho Falls Infectious Diseases, PLLC

Thomas Kovacs, MD

Role: PRINCIPAL_INVESTIGATOR

UCLA CURE Digestive Diseases Research Center

Alfred Bacon, MD

Role: PRINCIPAL_INVESTIGATOR

Christiana Care Health Systems

Kathleen Casey, MD

Role: PRINCIPAL_INVESTIGATOR

Jersey Shore University Medical Center

C. Douglas Cochran, MD

Role: PRINCIPAL_INVESTIGATOR

St. Luke's Hospital, Kansas City, Missouri

Donald Daly, MD

Role: PRINCIPAL_INVESTIGATOR

Vancouver Island Health Research Centre

Anil Dhar, MBBS

Role: PRINCIPAL_INVESTIGATOR

Windsor Regional Hospital

Gerald Evans, MD

Role: PRINCIPAL_INVESTIGATOR

Kingston Health Sciences Centre

Richard Greenberg, MD

Role: PRINCIPAL_INVESTIGATOR

University of Kentucky

Thomas Louie, MD

Role: PRINCIPAL_INVESTIGATOR

University of Calgary Foothills Medical Center

Thomas Nowak, MD

Role: PRINCIPAL_INVESTIGATOR

Central Indiana Gastroenterology Group

Jose Prieto, MD

Role: PRINCIPAL_INVESTIGATOR

Dr. Kiran C. Patel Research Institute

Daniel Schroeder, MD

Role: PRINCIPAL_INVESTIGATOR

Chest, Infectious Diseases and Critical Care Assoc., PC

Ann Silverman, MD

Role: PRINCIPAL_INVESTIGATOR

Henry Ford Health System

John Pullman, MD

Role: PRINCIPAL_INVESTIGATOR

Mercury Street Medical Group

Rodney J Mason, MD

Role: PRINCIPAL_INVESTIGATOR

LAC+USC Medical Center

Doria Grimard, MD

Role: PRINCIPAL_INVESTIGATOR

Centre de Sante et de Services Sociaux de Chicoutimi

Darrell Pardi, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

LAC/USC Medical Center

Los Angeles, California, United States

UCLA CURE Digestive Diseases Center

Los Angeles, California, United States

Kaiser Permanente Vaccine Study Center

Oakland, California, United States

Christiana Care Health Systems

Newark, Delaware, United States

Dr. Kiran C. Patel Research Institute

Tampa, Florida, United States

Idaho Falls Infectious Diseases, PLLC

Idaho Falls, Idaho, United States

Central Indiana Gastroenterology Group

Anderson, Indiana, United States

Chest, Infectious Diseases and Critical Care Assoc., PC

Des Moines, Iowa, United States

University of Kentucky Medical Center

Lexington, Kentucky, United States

Henry Ford Health System

West Bloomfield, Michigan, United States

Mayo Clinic

Rochester, Minnesota, United States

Saint Luke's Hospital of Kansas City

Kansas City, Missouri, United States

Saint James Healthcare

Butte, Montana, United States

Jersey Shore University Medical Center

Neptune City, New Jersey, United States

Mount Sinai Hospital

New York, New York, United States

All-Trials Clinical Research, LLC

Winston-Salem, North Carolina, United States

Summa Health System

Akron, Ohio, United States

Remington-Davis Clinical Research

Columbus, Ohio, United States

Rapid City Regional Hospital

Rapid City, South Dakota, United States

St. Lukes Episcopal Hospital

Houston, Texas, United States

Scott and White Memorial Hospital

Temple, Texas, United States

MultiCare Health System Research Services

Tacoma, Washington, United States

University of Calgary Foothills Medical Center

Calgary, Alberta, Canada

Vancouver Island Health Research Centre

Victoria, British Columbia, Canada

Health Sciences Centre, University of Manitoba

Winnepeg, Manitoba, Canada

Kingston General Hospital

Kingston, Ontario, Canada

Windsor Regional Hospital

Windsor, Ontario, Canada

Centre de Sante et Services Sociaux de Chicoutimi

Chicoutimi, Quebec, Canada

Centre Hospitalier Regional de Trois-Rivieres

Trois-Rivières, Quebec, Canada

Countries

United States; Canada

References

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.

Reference Type: DERIVED

PMID: 31411386 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27365387 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 20089970 (View on PubMed)

Other Identifiers

CA-GCDX-06-02

Identifier Type: -

Identifier Source: org_study_id