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)

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.