LB-7. Therapeutic Use of an Oral Suspension of VP20621, Spores of a Non-Toxigenic Clostridium difficile (NTCD) Strain, for Prevention of Recurrence of C. difficile Infection (CDI)
Session: Oral Abstract Session: Late Breaker Oral Abstracts
Saturday, October 5, 2013: 11:42 AM
Room: The Moscone Center: 102 (Gateway Ballroom)
Background: In Phase 1, VP20621 administered to volunteers following antibiotic treatment was well tolerated and led to high rates of NTCD colonization in stool. This Phase 2 study evaluated VP20621 when administered to patients following antibiotic treatment for CDI.

Methods: Adult subjects who had recovered from CDI and completed a course of metronidazole or oral vancomycin were randomized to receive once daily placebo or VP20621 spores (104 x 7days, 107 x 7days or 107 x 14days), beginning 1-2 days after the last day of antibiotic. C. difficile stool cultures (with testing of isolates for toxin by EIA) were performed at baseline (NTCD Day 1) and Weeks 1, 2, 3 and 6. Subjects were monitored for recurrent CDI (defined as ≥3 unformed stools within 24 hours, positive C. difficile stool assay and no other likely cause of diarrhea).

Results: 168 subjects were randomized and dosed: overall median age 59 years; 39% ≥65 years old; 62% female. There were no notable safety differences between the VP20621 dose groups. Mild-moderate headache was the only notable associated adverse event (2% placebo, 10% VP20621). Treatment-emergent serious adverse events: 7% placebo, 3% VP20621; none were related to study drug. Data in table are through study Week 6. 

Placebo

VP20621

104 x 7d

107 x 7d

107 x 14d

All VP20621 doses

n

43

41

43

41

125

NTCD detected in stool during 14 day administration period

0%

54%

79%

73%

72%

p value

<0.0001

<0.0001

<0.0001

<0.0001

CDI Recurrence

30%

15%

5%

15%

11%

p value

0.11

<0.01

0.10

<0.01

Antibacterial Use for CDI Treatment

33%

15%

9%

17%

14%

p value

0.06

0.02

0.14

<0.01

Diarrhea or loose stool of any severity or duration

77%

56%

58%

56%

57%

p value

0.05

0.09

0.02

0.02

 Conclusion: VP 20621 was well tolerated at all doses and reduced the incidence of CDI recurrence by ≥50% vs. placebo, with a similar reduction in need for antibacterial treatment for CDI. Dosing at 107 spores/day for 7 days appears to be sufficient for effective colonization. VP20621 is a novel biotherapeutic approach to prevention of CDI recurrence and potentially primary CDI as well which warrants further development.

Stephen Villano, MD, Clinical Research & Development, ViroPharma Incorporated, Exton, PA, John Armstrong, MD, Infection Control, Winchester Medical Center, Winchester, VA, Thomas Meyer, MD, Indiana University Health Arnett Hospital, Lafayette, IN, Christine Lee, MD, FRCPC, St. Joseph's Healthcare, Hamilton, ON, Canada, Michael Somero, MD, Somero Research, Palm Desert, CA, Stuart Cohen, MD, FIDSA, FSHEA, Division Of Infectious Diseases, University of California At Davis Medical Center, Sacramento, CA, Uma Murthy, MD, Syracuse VA Medical Center, Syracuse, NY, Andre Poirier, MD, MSc, Centre Hospitalier Regional de Trois-Rivieres, Trois-Rivieres, QC, Canada, Trevor Van Schooneveld, MD, University of Nebraska Medical Center, Omaha, NE, Darrell Pardi, MD, MS, Division Of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, Antonio Ramos, MD, Hospital Universitario Puerta de Hierro, Madrid, Spain, Michelle Barron, MD, Internal Medicine/Infectious Diseases, University of Colorado Denver, Aurora, CO and Dale Gerding, MD, Loyola University and Hines VA Hospital, Hines, IL

Disclosures:

S. Villano, ViroPharma Incorporated: Employee and Shareholder, Salary

J. Armstrong, ViroPharma Incorporated: Investigator, Research grant

T. Meyer, ViroPharma Incorporated: Investigator, Research grant

C. Lee, ViroPharma Incorporated: Investigator, Research grant

M. Somero, ViroPharma Incorporated: Investigator, Research grant

S. Cohen, ViroPharma Incorporated: Investigator, Research grant

U. Murthy, ViroPharma Incorporated: Investigator, Research grant

A. Poirier, ViroPharma Incorporated: Investigator, Research grant

T. Van Schooneveld, ViroPharma Incorporated: Investigator, Research grant

D. Pardi, ViroPharma Incorporated: Investigator, Research grant

A. Ramos, ViroPharma Incorporated: Investigator, Research grant

M. Barron, ViroPharma Incorporated: Investigator, Research grant

D. Gerding, ViroPharma Incorporated: Consultant and licensed patents, Consulting fee and Licensing agreement or royalty

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