Bezlotoxumab (MK-6072) Versus Placebo in Children With Clostridium Difficile Infection (CDI) (MK-6072-001)

NCT03182907 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: 6072-001MK-6072-0012017-000070-11
• Study Type: interventional
• Target: 148
• Locations: 17 countries
• Sites: 75

Brief Summary

The primary objectives of this study are to evaluate the pharmacokinetics (PK), safety, and tolerability of bezlotoxumab (MK-6072) in children aged 1 to \<18 years of age with a confirmed diagnosis of Clostridium difficile infection (CDI) who are receiving antibacterial drug treatment. The primary hypothesis is that the area under the concentration-time curve from 0 to infinity (AUC0-inf) of bezlotoxumab after treatment of pediatric participants with bezlotoxumab is similar when compared to the AUC0-inf of bezlotoxumab after treatment of adults with bezlotoxumab.

Conditions

Clostridium Difficile Infection

Outcome Measures

Primary Outcomes (3)

• Area Under the Concentration-Time Curve of Bezlotoxumab From Time 0 to Infinity (AUC0-inf)

  Blood samples were collected at specified intervals for the determination of AUC0-inf. AUC0-inf was defined as the area under the concentration-time curve of bezlotoxumab from time zero to infinity. Per protocol, AUC0-inf of bezlotoxumab was determined for each age cohort.

  Day 1 (2 hours postdose), Days 10, 29, 57, and 85

• Percentage of Participants Who Experienced an Adverse Event (AE)

  An AE was defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product and does not imply any judgment about causality. Per protocol, percentage of participants with AEs in the bezlotoxumab and placebo groups were presented.

  Up to approximately 12 weeks

• Percentage of Participants Who Discontinued Study Due to an AE

  An AE was defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product and does not imply any judgment about causality. Per protocol, percentage of participants who discontinued study due to AEs in the bezlotoxumab and placebo groups were presented.

  Up to approximately 12 weeks

Secondary Outcomes (6)

• Percentage of Participants Who Had a Clostridium Difficile Infection (CDI) Recurrence

  Up to approximately 12 Weeks

• Percentage of Participants Who Had a Sustained Clinical Response (SCR)

  Up to approximately 12 Weeks

• Percentage of High-Risk Participants Who Experienced a CDI Recurrence

  Up to approximately 12 Weeks

• Percentage of High-Risk Participants Who Experienced a SCR

  Up to approximately 12 Weeks

• Percentage of Participants Who Experienced One or More Infusion Related Reaction

  Up to approximately 24 hours after infusion on Day 1

Study Arms (2)

Bezlotoxumab

EXPERIMENTAL

Participants receive 10 mg of bezlotoxumab per kg body weight via a single 60-minute (±10 minutes) intravenous (IV) infusion on Day 1. Additionally, participants receive background antibacterial drug treatment (ABD) for 10-21 days per institutional guidelines, at the investigator's discretion. Dose may then be changed based on results from initial 12 participants.

Biological: Bezlotoxumab; Drug: Antibacterial drug treatment (ABD)

Placebo

PLACEBO COMPARATOR

Participants receive placebo for bezlotoxumab consisting of either 0.9% sodium chloride or 5% dextrose via a single 60-minute (±10 minutes) IV infusion on Day 1. Additionally, participants receive background ABD for 10-21 days per institutional guidelines, at the investigator's discretion.

Drug: Placebo; Drug: Antibacterial drug treatment (ABD)

Interventions

Bezlotoxumab BIOLOGICAL

A single intravenous (IV) infusion of 10 mg of bezlotoxumab per kg body weight. Dose may then be changed based on results from initial 12 participants.

Also known as: MK-6072

Bezlotoxumab

Placebo DRUG

A single IV infusion of placebo for bezlotoxumab consisting of either 0.9% sodium chloride or 5% dextrose.

Placebo

Antibacterial drug treatment (ABD) DRUG

ABD will be administered for 10-21 days including the duration of ABD prior to the screening visit, during the screening period, and after the infusion of study treatment, per institutional guidelines, at the investigator's discretion. ABD is defined as the receipt of oral metronidazole, oral vancomycin, intravenous (IV) metronidazole concurrent with oral vancomycin, oral fidaxomicin, or oral fidaxomicin concurrent with IV metronidazole.

Bezlotoxumab; Placebo

Eligibility Criteria

• Age: 1 Year - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• At screening has suspected or confirmed Clostridium difficile infection (CDI), and is receiving or is planning to receive a 10- to 21-day course of antibacterial drug treatment for CDI
• At study infusion has a diagnosis of CDI confirmed by a diagnostic assay which detects the presence of C. difficile toxin in stool, and is still receiving antibacterial drug treatment for CDI
• Female is not pregnant, and not breastfeeding; but if of childbearing potential agrees to follow contraceptive guidance during the treatment period and for at least 12 weeks after the last dose of study treatment
• Participant and/or parent or caregiver must be able to read, understand, and complete the daily diary

You may not qualify if:

• Has an uncontrolled chronic diarrheal illness
• Has a known hypersensitivity to bezlotoxumab, its active substance and/or any of its excipients
• At randomization, their planned course of antibacterial drug treatment for CDI is longer than 21 days
• At screening has received any listed prohibited prior and concomitant treatments and procedures
• Has previously participated in this study, has previously received bezlotoxumab, has received an experimental monoclonal antibody against C. difficile toxin B, or has received a vaccine directed against C. difficile or its toxins.
• Has received an investigational study agent within the previous 30 days, or is currently participating in or scheduled to participate in any other clinical study with an investigational agent during the 12-week study period

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (75)

Children's Hospital - Los Angeles ( Site 0021)

Los Angeles, California, 90027, United States

Location

UCSF Medical Center ( Site 0049)

San Francisco, California, 94158, United States

Location

Children's Hospital - Colorado ( Site 0013)

Aurora, Colorado, 80045, United States

Location

Children's Center for Digestive Healthcare ( Site 0052)

Atlanta, Georgia, 30342, United States

Location

University of Chicago ( Site 0019)

Chicago, Illinois, 60637, United States

Location

Our Lady of the Lake Hospital ( Site 0007)

Baton Rouge, Louisiana, 70808, United States

Location

The Johns Hopkins Rubenstein Child Health Building ( Site 0034)

Baltimore, Maryland, 21287, United States

Location

Tufts Medical Center-Floating Hospital for Children ( Site 0046)

Boston, Massachusetts, 02111, United States

Location

Mayo Clinic - Rochester ( Site 0004)

Rochester, Minnesota, 55905, United States

Location

Washington University ( Site 0037)

St Louis, Missouri, 63110, United States

Location

Columbia University Medical Center/ MSCHONY ( Site 0042)

New York, New York, 10032, United States

Location

SUNY Upstate Medical Center, University Hospital ( Site 0027)

Syracuse, New York, 13210, United States

Location

Montefiore Einstein Center ( Site 0041)

The Bronx, New York, 10467, United States

Location

Duke University Health System ( Site 0025)

Durham, North Carolina, 27710, United States

Location

Cincinnati Children's Hospital Medical Center ( Site 0024)

Cincinnati, Ohio, 45229, United States

Location

University Hospitals Cleveland Medical Center ( Site 0029)

Cleveland, Ohio, 44106, United States

Location

St. Jude Children's Research Hospital ( Site 0050)

Memphis, Tennessee, 38105, United States

Location

Vanderbilt University Medical Center ( Site 0022)

Nashville, Tennessee, 37232, United States

Location

The Children's Hospital of San Antonio ( Site 0009)

San Antonio, Texas, 78207, United States

Location

Primary Children's Hospital ( Site 0001)

Salt Lake City, Utah, 84113, United States

Location

Seattle Childrens Hospital ( Site 0028)

Seattle, Washington, 98105, United States

Location

Hospital Italiano de Buenos Aires. ( Site 2103)

Caba, Buenos Aires, C1199ABB, Argentina

Location

Hospital Privado de Cordoba ( Site 2102)

Córdoba, X5016KEH, Argentina

Location

Santa Casa de Misericordia de Belo Horizonte ( Site 0208)

Belo Horizonte, Minas Gerais, 30150-321, Brazil

Location

Hospital de Clinicas da Universidade Federal do Parana ( Site 0203)

Curitiba, Paraná, 80060-900, Brazil

Location

Hospital Pequeno Principe ( Site 0200)

Curitiba, Paraná, 80250-060, Brazil

Location

Hospital Universitario da Universidade Federal de Santa Maria ( Site 0209)

Santa Maria, Rio Grande do Sul, 97105-900, Brazil

Location

Instituto de Oncologia Pediatrica - GRAACC - Unifesp ( Site 0205)

São Paulo, 04039-001, Brazil

Location

Hospital Pablo Tobon Uribe-Infectology pediatric ( Site 2166)

Medellín, Antioquia, 05034, Colombia

Location

Fundacion Santa Fe de Bogota ( Site 2167)

Bogotá, Bogota D.C., 110111, Colombia

Location

Fundacion Cardioinfantil Instituto de Cardiologia ( Site 2163)

Bogotá, Bogota D.C., 110131, Colombia

Location

Fundacion Valle del Lili ( Site 2161)

Cali, Valle del Cauca Department, 760032, Colombia

Location

Centro Medico Imbanaco ( Site 2160)

Cali, Valle del Cauca Department, 760042, Colombia

Location

Fakultni Nemocnice Brno Bohunice ( Site 2000)

Brno, Brno-mesto, 61300, Czechia

Location

Fakultni nemocnice Plzen ( Site 2001)

Plzen Lochotin, Plzeň Region, 304 60, Czechia

Location

2. LF UK a FN Motol ( Site 2003)

Prague, 150 06, Czechia

Location

Universitaetsklinikum Muenster ( Site 1400)

Münster, North Rhine-Westphalia, 48149, Germany

Location

Universitaetsklinikum Hamburg Eppendorf ( Site 1402)

Hamburg, 20246, Germany

Location

SZTE Szent-Gyorgyi Albert Klinikai Kozpont ( Site 2200)

Szeged, Csongrád megye, 6720, Hungary

Location

Semmelweis University-II.sz. Gyermekgyógyászati Klinika ( Site 2201)

Budapest, 1094, Hungary

Location

Del-pesti Centrumkorhaz Orszagos Hematologiai es Infektologiai Intezet ( Site 2202)

Budapest, 1097, Hungary

Location

Sabah Womens & Childrens Hospital ( Site 3101)

Kota Kinabalu, Sabah, 88996, Malaysia

Location

Hospital Kuala Lumpur ( Site 3100)

Kuala Lumpur, 50300, Malaysia

Location

Hospital Universitario "Dr. Jose Eleuterio Gonzalez" ( Site 0508)

Monterrey, Nuevo León, 64400, Mexico

Location

Instituto Tecnologico y de Estudios Superiores de Monterrey ( Site 0502)

Monterrey, Nuevo León, 64710, Mexico

Location

Instituto Nacional de Pediatria ( Site 0503)

Mexico City, 04530, Mexico

Location

Hospital Infantil de Mexico Federico Gomez ( Site 0501)

Mexico City, 06720, Mexico

Location

Haukeland universitetssykehus ( Site 1501)

Bergen, Vestfold, 5053, Norway

Location

Oslo universitetssykehus ( Site 1500)

Oslo, 0372, Norway

Location

Wojewodzki Szpital Obserwacyjno Zakazny ( Site 2404)

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-030, Poland

Location

Instytut Pomnik Centrum Zdrowia Dziecka ( Site 2406)

Warsaw, Masovian Voivodeship, 04-730, Poland

Location

SPZOZ im. Dzieci Warszawy w Dziekanowie Lesnym ( Site 2405)

Łomianki, Masovian Voivodeship, 05-092, Poland

Location

Wojewodzki Specjalistyczny Szpital Dzieciecy ( Site 2410)

Olsztyn, Warmian-Masurian Voivodeship, 10-561, Poland

Location

Wojewodzki Specjalistyczny Szpital im. dr W. Bieganskiego w Lodzi ( Site 2400)

Lodz, Łódź Voivodeship, 91-347, Poland

Location

Hospital de Braga ( Site 1600)

Braga, 4710-243, Portugal

Location

Inst. Portugues de Oncologia de Lisboa Francisco Gentil EPE ( Site 1605)

Lisbon, 1099-023, Portugal

Location

Centro Hospitalar de Lisboa Central EPE. Hospital D. Estefania ( Site 1601)

Lisbon, 1169-045, Portugal

Location

Instituto Portugues de Oncologia Do Porto Francisco Gentil E.P.E. ( Site 1603)

Porto, 4200-072, Portugal

Location

Spitalul Clinic de Boli Infectioase Cluj-Napoca ( Site 2502)

Cluj-Napoca, Cluj, 400348, Romania

Location

Institutul National de Boli Infectioase Prof. Dr. Matei Bals ( Site 2501)

Bucharest, 021105, Romania

Location

Spitalul Clinic de Boli Infectioase si Tropicale Dr. Victor Babes ( Site 2500)

Bucharest, 030303, Romania

Location

Spitalul Clinic de Boli Infectioase Constanta ( Site 2504)

Constanța, 900708, Romania

Location

Phoenix Pharma Pty Ltd ( Site 2607)

Port Elizabeth, Eastern Cape, 6001, South Africa

Location

Johese Clinical Research ( Site 2605)

Centurion, Gauteng, 1692, South Africa

Location

Chris Hani Baragwanath Academic Hospital ( Site 2602)

Johannesburg, Gauteng, 1860, South Africa

Location

Molotlegi Street ( Site 2603)

Pretoria, Gauteng, 0208, South Africa

Location

Red Cross War Memorial Children's Hospital ( Site 2601)

Cape Town, Western Cape, 7700, South Africa

Location

Hospital Universitario Sant Joan de Deu ( Site 1704)

Esplugues de Llobregat, Barcelona, 08950, Spain

Location

Hospital Infantil Universitario Nino Jesus ( Site 1701)

Madrid, 28009, Spain

Location

Hospital Universitario La Paz ( Site 1703)

Madrid, 28046, Spain

Location

Hospital Universitario Virgen del Rocio ( Site 1705)

Seville, 41013, Spain

Location

ITCC Barnokologen Astrid Lindgrens Barnsjukhus NKS ( Site 1800)

Stockholm, Stockholm County, 17176, Sweden

Location

Barncancercentrum ( Site 1801)

Gothenburg, Västra Götaland County, 416 85, Sweden

Location

Southampton General Hospital ( Site 1900)

Southampton, Worcestershire, SO16 6YD, United Kingdom

Location

Leeds Teaching Hospitals NHS Trust ( Site 1901)

Leeds, LS1 3EX, United Kingdom

Location

Related Publications (1)

• Sferra TJ, Merta T, Neely M, Murta de Oliveira C, Lassaletta A, Fortuny Guasch C, Dorr MB, Winchell G, Su FH, Perko S, Fernsler D, Waskin H, Holden SR. Double-Blind, Placebo-Controlled Study of Bezlotoxumab in Children Receiving Antibacterial Treatment for Clostridioides difficile Infection (MODIFY III). J Pediatric Infect Dis Soc. 2023 Jun 30;12(6):334-341. doi: 10.1093/jpids/piad031.

  PMID: 37389891 RESULT

Related Links

• Merck Clinical Trial Information

MeSH Terms

Conditions

Clostridium Infections

Interventions

bezlotoxumab

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2017
• First Posted: June 9, 2017
• Study Start: March 27, 2018
• Primary Completion: May 12, 2022
• Study Completion: May 12, 2022
• Last Updated: July 27, 2023
• Results First Posted: June 7, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will share

Locations

CZ (3); ME (4); PL (5); DE (2); NO (2); AR (2); ZA (5); US (21); BR (5); PT (4); CO (5); SE (2); RO (4); HU (3); ES (4); GB (2); MY (2)