Bezlotoxumab for Clostridioides difficile infection

BEZLOTOXUMAB YIELDED OUTCOMES BY ADDRESSING PERSONALIZED NEEDS IN CLOSTRIDIOIDES DIFFICILE INFECTION: THE BEYOND DOUBLE-BLIND RANDOMIZED CLINICAL TRIAL

Status

Active, not recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2021-005473-10-GR

Enrollment

Registered

2021-10-21

Start date

2021-11-24

Completion date

Unknown

Last updated

2025-02-17

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Clostridioides difficile Infection (CDI) MedDRA version: 24.0 Level: LLT Classification code 10085158 Term: Clostridioides difficile infection System Organ Class: 100000004862

Interventions

Trade Name: ZINPLAVA Product Name: Bezlotoxumab Pharmaceutical Form: Concentrate for solution for infusion Pharmaceutical form of the placebo: Solution for infusion Route of administration of the plac

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. Age equal or above 18 years 2. Both genders 3. Written informed consent provided by the patient or by their legal representative in case of patients unable to consent 4. In case of non-menopausal women, unwillingness to become pregnant during the study period. Women of child-bearing potential will be screened by a urine pregnancy test before inclusion in the study. 5. Diarrhea defined as at least 3 episodes of unformed stool in the past 24hours. 6. Positive stool for C.difficile. This is defined as any stool sample positive for the presence of glutamate dehydrogenase (GDH) and for the presence of toxin A and/or B. 7. Positive BEYOND score i.e. meeting any of the following: Gene score for susceptibility to CDI more than 53. The score is provided by the following equation: (Carriage of C allele of rs12148744 x 27) – (carriage of C allele of rs714024 x 27) - (carriage of C allele of rs721059 x 29) + (carriage of T allele of rs4311028 x 33) – (carriage of A allele of rs62183547 x 25) + (carriage of C allele of rs1128266 x 12) - (carriage of T allele of rs4279595 x 17) + (carriage of G allele of rs175006 x 11) + (carriage of T allele of rs3859214 x 17) + (carriage of G allele of rs7222870 x 15) – (carriage of G allele of rs5086600 x 9) + (carriage of T allele of rs7240534 x 12) + (carriage of G allele of rs20911172 x 11) - (carriage of C allele of rs17680671 x 17) OR Score provided by the following equation more than 9= [Hemoglobin 64.5 mg/dl x 14] + [serum interleukin-8 >227 pg/ml x 19] – [carriage of G allele of rs2091172 x 17] OR More than 3log10 of gammaproteobacteria or Enterobacteriaceae or Enterobacteriales in the stool Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 22 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 22

Exclusion criteria

Exclusion criteria: • Age below 18 years • Denial for written informed consent • Known allergy to bezlotoxumab • Pregnancy or lactation. Women of child-bearing potential will be screened by a urine pregnancy test before inclusion in the study

Design outcomes

Primary

Measure	Time frame
Main Objective: Previous data from our group have shown that integrated information from SNPs of the host DNA, IL-8 and the enrichment of the stool microbiome can indicate the patients with infection by Clostridioides difficile (CDI) at risk for unfavorable outcome. This integrated information is forming the BEYOND score. The aim of the BEYOND RCT is to investigate if adjunctive bezlotoxumab treatment to the current standard-of-care may decrease the likelihood of unfavorable outcome for patients who score positive by the BEYOND score.;Secondary Objective: Not applicable;Primary end point(s): The superiority of bezlotoxumab over placebo to reduce the incidence of unfavorable outcome. Unfavorable outcome is defined as any of the following: progression into organ dysfunction; relapse of CDI; and death. The primary endpoint is tested on Day 40 from start of blind treatment. Organ dysfunction is defined as any increase of the baseline total SOFA score by at least 2 points. Need for colectomy or admission in the Intensive Care Unit counts as organ dysfunction.;Timepoint(s) of evaluation of this end point: Day 40	—

Measure

Time frame

Main Objective: Previous data from our group have shown that integrated information from SNPs of the host DNA, IL-8 and the enrichment of the stool microbiome can indicate the patients with infection by Clostridioides difficile (CDI) at risk for unfavorable outcome. This integrated information is forming the BEYOND score. The aim of the BEYOND RCT is to investigate if adjunctive bezlotoxumab treatment to the current standard-of-care may decrease the likelihood of unfavorable outcome for patients who score positive by the BEYOND score.;Secondary Objective: Not applicable;Primary end point(s): The superiority of bezlotoxumab over placebo to reduce the incidence of unfavorable outcome. Unfavorable outcome is defined as any of the following: progression into organ dysfunction; relapse of CDI; and death. The primary endpoint is tested on Day 40 from start of blind treatment. Organ dysfunction is defined as any increase of the baseline total SOFA score by at least 2 points. Need for colectomy or admission in the Intensive Care Unit counts as organ dysfunction.;Timepoint(s) of evaluation of this end point: Day 40

—

Secondary

Measure	Time frame
Secondary end point(s): The superiority of bezlotoxumab over placebo when given for CDI of high likelihood for unfavorable outcome on the following: • Incidence of organ failure and time to first organ failure • Time to relapse of CDI • Survival time • Cost of hospitalization • Validation of the BEYOND score;Timepoint(s) of evaluation of this end point: Day 40	—

Countries

Greece

Contacts

Public ContactPresident of the Board

Hellenic Institute for the Study of Sepsis

insepsis@otenet.gr00302107480662

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026