Clinical Data
Help take control with ZINPLAVA: Reduce CDI recurrence in high-risk adult patients receiving CDI antibiotics
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Help reduce CDI recurrence in high-risk adult patients receiving CDI antibiotics
Adding ZINPLAVA helped patients to achieve sustained clinical response* vs SoC antibiotics alone
- In MODIFY I, the numerical increase in sustained clinical response did not reach the level of significance.
- In MODIFY II, statistically significant increases were achieved.
*Sustained clinical response was defined as clinical cure of the presenting CDI episode and no CDI recurrence through 12 weeks after infusion.
Sustained clinical response through 12 weeks1
The reasons for not achieving sustained clinical response were either recurrence or clinical failure.1
CDI recurrence through 12 weeks1
Clinical failure*
a95% confidence intervals were computed as a measure of strength of association between the endpoint and treatment effect rather than formal tests of hypotheses.
bComparisons between treatment and placebo with regard to the primary end point were performed at a two-sided alpha level of 0.025 in MODIFY I.7
cComparisons between treatment and placebo with regard to the primary end point were performed at a two-sided alpha level of 0.050 in MODIFY II.7
*Reasons for clinical failure include: diarrhea during at least one of 2 consecutive days following end of SoC therapy (MODIFY I, n=39; MODIFY II, n=26); SoC therapy regimen >14 days (MODIFY I, n=36; MODIFY II, n=27); or no information regarding loose stool counts following end of SoC therapy (MODIFY I, n=12; MODIFY II, n=16).2 Clinical cure was defined as no diarrhea for 2 consecutive days following the completion of a ≤14-day SoC regimen.
- Fewer patients receiving ZINPLAVA plus SoC CDI antibiotics had a CDI recurrence compared with SoC CDI antibiotics alone.
- In MODIFY I, the RRR of CDI recurrence was 37%.
- In MODIFY II, the RRR of CDI recurrence was 39%.
- In MODIFY I, the clinical cure rate of the presenting CDI episode was lower in the ZINPLAVA plus SoC CDI antibiotics arm compared to placebo plus SoC CDI antibiotics arm. In MODIFY II, the clinical cure rate was lower in the placebo plus SoC CDI antibiotics arm compared to the ZINPLAVA plus SoC CDI antibiotics arm.
- Additional analyses showed that by 3 weeks poststudy drug infusion, the clinical cure rates of the presenting CDI episode were similar between treatment arms.
- Patients in the ZINPLAVA and placebo arms who did not achieve clinical cure of the presenting CDI episode received a mean of 18 to 19 days of SoC and had a mean of 4 additional days of diarrhea following completion of SoC.
Study design
Efficacy and safety of ZINPLAVA were investigated in 2 randomized, double-blind, placebo-controlled, multicenter Phase 3 trials in 1,554 adult patients. Enrolled patients had a confirmed diagnosis of CDI, defined as diarrhea (≥3 loose bowel movements in ≤24 hours) and a positive stool test for toxigenic C. difficile from a stool sample collected ≤7 days before study entry. Patients received a 10- to 14-day course of oral CDI antibiotics (metronidazole, vancomycin, or fidaxomicin). Patients were randomized to receive either a single 10-mg/kg (body weight) IV infusion of ZINPLAVA (n=781) or placebo IV (n=773) during the course of the CDI antibiotic therapy. Patients were assessed for clinical cure of the presenting CDI episode, defined as no diarrhea for 2 consecutive days following the completion of a ≤14-day CDI regimen. Patients who achieved clinical cure were then assessed for recurrence of CDI through 12 weeks following administration of the infusion of ZINPLAVA or placebo.
Definitions
CDI = Clostridium difficile infection
CI = confidence interval
IV = intravenous
NS = not significant
RRR = relative risk reduction
SoC = standard of care
References
1. Wilcox MH, Gerding DN, Poxton IR, et al. Bezlotoxumab for prevention of recurrent Clostridium difficile infection. N Engl J Med. 2017;376(4):305–317. doi:10.1056/NEJMoa1602615.
2. Data available on request from Merck & Co, Inc., Professional Services-DAP, WP1-27, PO Box 4, West Point, PA 19486-0004. Please specify information package US-MKB-00157.
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