Clinical trial NCT03182907: Bezlotoxumab (MK-6072) Versus Placebo in Children With Clostridium Difficile Infection (CDI) (MK-6072-001)
Official title: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of a Single Infusion of Bezlotoxumab (MK-6072, Human Monoclonal Antibody to C. Difficile Toxin B) in Children Aged 1 to <18 Years Receiving Antibacterial Drug Treatment for C. Difficile Infection (MODIFY III)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Clostridium Difficile Infection
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2017-06-09
Enrollment: 148
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Detailed description: Historical adult pharmacokinetic data is from NCT01241552 and NCT01513239.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Area Under the Concentration-Time Curve of Bezlotoxumab From Time 0 to Infinity (AUC0-inf)
timeFrame: Day 1 (2 hours postdose), Days 10, 29, 57, and 85
measure: Percentage of Participants Who Experienced an Adverse Event (AE)
timeFrame: Up to approximately 12 weeks
measure: Percentage of Participants Who Discontinued Study Due to an AE
timeFrame: Up to approximately 12 weeks
Secondary outcomes:
measure: Percentage of Participants Who Had a Clostridium Difficile Infection (CDI) Recurrence
timeFrame: Up to approximately 12 Weeks
measure: Percentage of Participants Who Had a Sustained Clinical Response (SCR)
timeFrame: Up to approximately 12 Weeks
measure: Percentage of High-Risk Participants Who Experienced a CDI Recurrence
timeFrame: Up to approximately 12 Weeks
measure: Percentage of High-Risk Participants Who Experienced a SCR
timeFrame: Up to approximately 12 Weeks
measure: Percentage of Participants Who Experienced One or More Infusion Related Reaction
timeFrame: Up to approximately 24 hours after infusion on Day 1
measure: Percentage of Participants Who Had Positive Antibodies to Bezlotoxumab
timeFrame: Up to approximately 12 Weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital - Los Angeles ( Site 0021)
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center ( Site 0049)
state: California
city: Aurora
country: United States
facility: Children's Hospital - Colorado ( Site 0013)
state: Colorado
city: Atlanta
country: United States
facility: Children's Center for Digestive Healthcare ( Site 0052)
state: Georgia
city: Chicago
country: United States
facility: University of Chicago ( Site 0019)
state: Illinois
city: Baton Rouge
country: United States
facility: Our Lady of the Lake Hospital ( Site 0007)
state: Louisiana
city: Baltimore
country: United States
facility: The Johns Hopkins Rubenstein Child Health Building ( Site 0034)
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center-Floating Hospital for Children ( Site 0046)
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic - Rochester ( Site 0004)
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University ( Site 0037)
state: Missouri
city: Bronx
country: United States
facility: Montefiore Einstein Center ( Site 0041)
state: New York
city: New York
country: United States
facility: Columbia University Medical Center/ MSCHONY ( Site 0042)
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical Center, University Hospital ( Site 0027)
state: New York
city: Durham
country: United States
facility: Duke University Health System ( Site 0025)
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center ( Site 0024)
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center ( Site 0029)
state: Ohio
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital ( Site 0050)
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center ( Site 0022)
state: Tennessee
city: San Antonio
country: United States
facility: The Children's Hospital of San Antonio ( Site 0009)
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Hospital ( Site 0001)
state: Utah
city: Seattle
country: United States
facility: Seattle Childrens Hospital ( Site 0028)
state: Washington
city: Caba
country: Argentina
facility: Hospital Italiano de Buenos Aires. ( Site 2103)
state: Buenos Aires
city: Cordoba
country: Argentina
facility: Hospital Privado de Cordoba ( Site 2102)
city: Belo Horizonte
country: Brazil
facility: Santa Casa de Misericordia de Belo Horizonte ( Site 0208)
state: Minas Gerais
city: Curitiba
country: Brazil
facility: Hospital de Clinicas da Universidade Federal do Parana ( Site 0203)
state: Parana
city: Curitiba
country: Brazil
facility: Hospital Pequeno Principe ( Site 0200)
state: Parana
city: Santa Maria
country: Brazil
facility: Hospital Universitario da Universidade Federal de Santa Maria ( Site 0209)
state: Rio Grande Do Sul
city: Sao Paulo
country: Brazil
facility: Instituto de Oncologia Pediatrica - GRAACC - Unifesp ( Site 0205)
city: Medellin
country: Colombia
facility: Hospital Pablo Tobon Uribe-Infectology pediatric ( Site 2166)
state: Antioquia
city: Bogota
country: Colombia
facility: Fundacion Cardioinfantil Instituto de Cardiologia ( Site 2163)
state: Distrito Capital De Bogota
city: Bogotá
country: Colombia
facility: Fundacion Santa Fe de Bogota ( Site 2167)
state: Distrito Capital De Bogota
city: Cali
country: Colombia
facility: Fundacion Valle del Lili ( Site 2161)
state: Valle Del Cauca
city: Cali
country: Colombia
facility: Centro Medico Imbanaco ( Site 2160)
state: Valle Del Cauca
city: Brno
country: Czechia
facility: Fakultni Nemocnice Brno Bohunice ( Site 2000)
state: Brno-mesto
city: Plzen Lochotin
country: Czechia
facility: Fakultni nemocnice Plzen ( Site 2001)
state: Plzensky Kraj
city: Praha 5
country: Czechia
facility: 2. LF UK a FN Motol ( Site 2003)
city: Muenster
country: Germany
facility: Universitaetsklinikum Muenster ( Site 1400)
state: Nordrhein-Westfalen
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg Eppendorf ( Site 1402)
city: Szeged
country: Hungary
facility: SZTE Szent-Gyorgyi Albert Klinikai Kozpont ( Site 2200)
state: Csongrad
city: Budapest
country: Hungary
facility: Semmelweis University-II.sz. Gyermekgyógyászati Klinika ( Site 2201)
city: Budapest
country: Hungary
facility: Del-pesti Centrumkorhaz Orszagos Hematologiai es Infektologiai Intezet ( Site 2202)
city: Kota Kinabalu
country: Malaysia
facility: Sabah Womens & Childrens Hospital ( Site 3101)
state: Sabah
city: Kuala Lumpur
country: Malaysia
facility: Hospital Kuala Lumpur ( Site 3100)
city: Monterrey
country: Mexico
facility: Hospital Universitario "Dr. Jose Eleuterio Gonzalez" ( Site 0508)
state: Nuevo Leon
city: Monterrey
country: Mexico
facility: Instituto Tecnologico y de Estudios Superiores de Monterrey ( Site 0502)
state: Nuevo Leon
city: Mexico City
country: Mexico
facility: Instituto Nacional de Pediatria ( Site 0503)
city: Mexico City
country: Mexico
facility: Hospital Infantil de Mexico Federico Gomez ( Site 0501)
city: Bergen
country: Norway
facility: Haukeland universitetssykehus ( Site 1501)
state: Vestfold
city: Oslo
country: Norway
facility: Oslo universitetssykehus ( Site 1500)
city: Bydgoszcz
country: Poland
facility: Wojewodzki Szpital Obserwacyjno Zakazny ( Site 2404)
state: Kujawsko-pomorskie
city: Lodz
country: Poland
facility: Wojewodzki Specjalistyczny Szpital im. dr W. Bieganskiego w Lodzi ( Site 2400)
state: Lodzkie
city: Lomianki
country: Poland
facility: SPZOZ im. Dzieci Warszawy w Dziekanowie Lesnym ( Site 2405)
state: Mazowieckie
city: Warszawa
country: Poland
facility: Instytut Pomnik Centrum Zdrowia Dziecka ( Site 2406)
state: Mazowieckie
city: Olsztyn
country: Poland
facility: Wojewodzki Specjalistyczny Szpital Dzieciecy ( Site 2410)
state: Warminsko-mazurskie
city: Braga
country: Portugal
facility: Hospital de Braga ( Site 1600)
city: Lisboa
country: Portugal
facility: Inst. Portugues de Oncologia de Lisboa Francisco Gentil EPE ( Site 1605)
city: Lisboa
country: Portugal
facility: Centro Hospitalar de Lisboa Central EPE. Hospital D. Estefania ( Site 1601)
city: Porto
country: Portugal
facility: Instituto Portugues de Oncologia Do Porto Francisco Gentil E.P.E. ( Site 1603)
city: Cluj-Napoca
country: Romania
facility: Spitalul Clinic de Boli Infectioase Cluj-Napoca ( Site 2502)
state: Cluj
city: Bucuresti
country: Romania
facility: Institutul National de Boli Infectioase Prof. Dr. Matei Bals ( Site 2501)
city: Bucuresti
country: Romania
facility: Spitalul Clinic de Boli Infectioase si Tropicale Dr. Victor Babes ( Site 2500)
city: Constanta
country: Romania
facility: Spitalul Clinic de Boli Infectioase Constanta ( Site 2504)
city: Port Elizabeth
country: South Africa
facility: Phoenix Pharma Pty Ltd ( Site 2607)
state: Eastern Cape
city: Centurion
country: South Africa
facility: Johese Clinical Research ( Site 2605)
state: Gauteng
city: Johannesburg
country: South Africa
facility: Chris Hani Baragwanath Academic Hospital ( Site 2602)
state: Gauteng
city: Pretoria
country: South Africa
facility: Molotlegi Street ( Site 2603)
state: Gauteng
city: Cape Town
country: South Africa
facility: Red Cross War Memorial Children's Hospital ( Site 2601)
state: Western Cape
city: Esplugues de Llobregat
country: Spain
facility: Hospital Universitario Sant Joan de Deu ( Site 1704)
state: Barcelona
city: Madrid
country: Spain
facility: Hospital Infantil Universitario Nino Jesus ( Site 1701)
city: Madrid
country: Spain
facility: Hospital Universitario La Paz ( Site 1703)
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio ( Site 1705)
city: Stockholm
country: Sweden
facility: ITCC Barnokologen Astrid Lindgrens Barnsjukhus NKS ( Site 1800)
state: Stockholms Lan
city: Goteborg
country: Sweden
facility: Barncancercentrum ( Site 1801)
state: Vastra Gotalands Lan
city: Southampton
country: United Kingdom
facility: Southampton General Hospital ( Site 1900)
state: Worcestershire
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals NHS Trust ( Site 1901)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.