for 12 weeks following the infusion. The day of the infusion of ZINPLAVA or placebo ranged from prior to the start of antibacterial therapy up to day 14 of treatment, with a median on day 3.
The baseline characteristics of the 781 patients receiving ZINPLAVA and 773 receiving placebo were generally similar across treatment groups. The median age was 65 years, 85 % were white, 57 % were female, and 68 % were inpatients. A similar proportion of patients were receiving oral metronidazole (48 %) or oral vancomycin (48 %) and only 4 % were receiving fidaxomicin as antibacterial treatment for CDI.
The CDI recurrence rates are shown in Table 2.
Table 2: CDI Recurrence Rate Through 12 Weeks After Infusion
(MODIFY I and MODIFY II, Full Analysis Set*)
ZINPLAVA with SoC†
Percent (n/N)
Placebo with SoC†
Percent (n/N)
Adjusted Difference (95% CI)‡
p-value
16.5 (129/781)
26.6 (206/773)
-10.0 (-14.0, -6.0)
<0.0001
n = Number of patients in the analysis population meeting the criteria for endpoint
N = Number of patients included in the analysis population
* Full Analysis Set = a subset of all randomised patients with exclusions for: (i) did not receive infusion of study medication, (ii) did not have a positive local stool test for toxigenic C. difficile; (iii) did not receive protocol defined standard of care therapy within a 1 day window of the infusion; (iiii) GCP non-compliance
† SoC = Standard of Care antibacterial (metronidazole or vancomycin or fidaxomicin)
‡ One sided p-value based on the Miettinen and Nurminen method stratified by protocol (MODIFY I and MODIFY II), SoC antibacterial (metronidazole vs. vancomycin vs. fidaxomicin) and hospitalization status (inpatient vs. outpatient)
Table 3 shows the results of a prospectively planned combined analysis of the CDI recurrence rates in pre-specified subgroups of patients at high risk for CDI recurrence across the two Phase 3 Trials. Overall, 51 % were ≥ 65 years, 29% were ≥ 75 years and 39 % received one or more systemic antibacterial agents during the 12 week follow-up period. Of the total 28 % had one or more episodes of CDI within the six months prior to the episode under treatment (18 % of the patients had one, 7 % had two and a few patients had 3 or more prior episodes). Twenty one (21) percent of the patients were immunocompromised and 16 % presented with clinically severe CDI. Among the 976/1554 (62 %) patients who had a positive baseline stool culture for C. difficile a hypervirulent strain (ribotypes 027, 078 or 244) was isolated in 22 % (217 of 976 patients), of which the majority (87 %, 189 of 217 strains) were ribotype 027.
These patients presented with risk factors primarily but not exclusively associated with higher risk of CDI recurrence. Efficacy results did not point towards a benefit of ZINPLAVA in patients with no known risk factors for CDI.
Table 3: CDI Recurrence Rate by Risk Factor Subgroup
(MODIFY I and MODIFY II, Full Analysis Set*)
Characteristic at study entry
ZINPLAVA with SoC†
Percent (n/m)
Placebo with SoC†
Percent (n/m)
Difference (95% CI)‡
Age ≥ 65 years
15.4 (60/390)
31.4 (127/405)
-16.0 (-21.7, -10.2)
History of one or more episodes of CDI in past 6 months
25.0 (54/216)
41.1 (90/219)
-16.1 (-24.7, -7.3)
Immunocompromised§
14.6 (26/178)
27.5 (42/153)
-12.8 (-21.7, -4.1)
Severe CDI¶
10.7 (13/122)
22.4 (28/125)
-11.7 (-21.1, -2.5)
Infected with a hypervirulent stra |
