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

• ClinicalTrials.gov Identifier: NCT03182907
• Recruitment Status: Recruiting
• First Posted: June 9, 2017
• Last Update Posted: October 7, 2021
• Sponsor: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Merck Sharp & Dohme Corp.

Study Description

Brief Summary:

The primary objectives of this study are to evaluate the pharmacokinetics (PK), safety, and tolerability of bezlotoxumab 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,

Condition or disease	Intervention/treatment	Phase
Clostridium Difficile Infection	Biological: Bezlotoxumab; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 192 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• 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)
• Actual Study Start Date: March 27, 2018
• Estimated Primary Completion Date: May 9, 2022
• Estimated Study Completion Date: May 9, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Bezlotoxumab; 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.	Biological: Bezlotoxumab; 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.; Other Name: MK-6072
Placebo Comparator: Placebo; A single IV infusion of placebo for bezlotoxumab consisting of either 0.9% sodium chloride or 5% dextrose	Drug: Placebo; A single IV infusion of placebo for bezlotoxumab consisting of either 0.9% sodium chloride or 5% dextrose.

Outcome Measures

Primary Outcome Measures :

1. Concentration time curve of bezlotoxumab [ Time Frame: Day 1 (2 hrs after infusion), Days 10, 29, 57, and 85 ]
   Area under the concentration time curve from time 0 to infinity (AUC0-inf) of serum bezlotoxumab
2. Adverse events (AEs) [ Time Frame: Up to Day 90 ]
   Percentage of participants experiencing AEs
3. Discontinuing medication [ Time Frame: Day 1 ]
   Percentage of participants discontinuing study medication due to an AE

Secondary Outcome Measures :

1. Clostridium difficile infection (CDI) recurrence [ Time Frame: Up to Week 12 ]
   Percentage of participants who have a CDI recurrence within 12 weeks of study medication infusion.
2. Sustained clinical response [ Time Frame: Up to Week 12 ]
   Percentage of participants with sustained clinical response within 12 weeks of study medication infusion.
3. CDI recurrence and sustained clinical response [ Time Frame: Up to Week 12 ]
   Percentage of participants who have a CDI recurrence and who achieve sustained clinical response within 12 weeks of study medication infusion in participants at high risk of CDI recurrence.
4. Infusion-related reactions [ Time Frame: Up to 24 hours ]
   Percentage of participants experiencing 1 or more infusion-related reactions within 24 hours following the start of study medication infusion.
5. Positive antibodies to bezlotoxumab [ Time Frame: Up to Week 12 ]
   Percentage of participants with treatment-emergent positive antibodies to bezlotoxumab in serum through 12 weeks following a single dose of bezlotoxumab.

Eligibility Criteria

• Ages Eligible for Study: 1 Year to 17 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• At screening has suspected or confirmed 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

Contacts and Locations

Contacts

Contact: Toll Free Number; 1-888-577-8839; Trialsites@merck.com

Locations

United States, California

Children's Hospital - Los Angeles ( Site 0021); Recruiting

Los Angeles, California, United States, 90027

Contact: Study Coordinator 323-361-2509

UCSF Medical Center ( Site 0049); Recruiting

San Francisco, California, United States, 94158

Contact: Study Coordinator 415-476-1539

United States, Colorado

Children's Hospital - Colorado ( Site 0013); Completed

Aurora, Colorado, United States, 80045

United States, Illinois

University of Chicago ( Site 0019); Recruiting

Chicago, Illinois, United States, 60637

Contact: Study Coordinator 773-702-7087

United States, Louisiana

Our Lady of the Lake Hospital ( Site 0007); Recruiting

Baton Rouge, Louisiana, United States, 70808

Contact: Study Coordinator 225-765-4365

United States, Maryland

The Johns Hopkins Rubenstein Child Health Building ( Site 0034); Recruiting

Baltimore, Maryland, United States, 21287

Contact: Study Coordinator 410-614-2949

United States, Massachusetts

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

Boston, Massachusetts, United States, 02111

Contact: Study Coordinator 617-636-0186

United States, Minnesota

Mayo Clinic - Rochester ( Site 0004); Completed

Rochester, Minnesota, United States, 55905

United States, Missouri

Washington University ( Site 0037); Recruiting

Saint Louis, Missouri, United States, 63110

Contact: Study Coordinator 314-747-5128

United States, New York

Montefiore Einstein Center ( Site 0041); Completed

Bronx, New York, United States, 10467

Columbia University Medical Center/ MSCHONY ( Site 0042); Recruiting

New York, New York, United States, 10032

Contact: Study Coordinator 212-342-3647

SUNY Upstate Medical Center, University Hospital ( Site 0027); Completed

Syracuse, New York, United States, 13210

United States, North Carolina

Duke University Health System ( Site 0025); Recruiting

Durham, North Carolina, United States, 27710

Contact: Study Coordinator 919-668-4855

United States, Ohio

Cincinnati Children's Hospital Medical Center ( Site 0024); Recruiting

Cincinnati, Ohio, United States, 45229

Contact: Study Coordinator 513-636-7499

University Hospitals Cleveland Medical Center ( Site 0029); Recruiting

Cleveland, Ohio, United States, 44106

Contact: Study Coordinator 216-844-1765

United States, Tennessee

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

Memphis, Tennessee, United States, 38105

Contact: Study Coordinator 901-595-3300

Vanderbilt University Medical Center ( Site 0022); Recruiting

Nashville, Tennessee, United States, 37232

Contact: Study Coordinator 615-343-2877

United States, Texas

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

San Antonio, Texas, United States, 78207

Contact: Study Coordinator 210-704-4708

United States, Utah

Primary Children's Hospital ( Site 0001); Completed

Salt Lake City, Utah, United States, 84113

United States, Washington

Seattle Childrens Hospital ( Site 0028); Recruiting

Seattle, Washington, United States, 98105

Contact: Study Coordinator 206-884-5086

Argentina

Hospital Italiano de Buenos Aires. ( Site 2103); Recruiting

Caba, Buenos Aires, Argentina, C1199ABB

Contact: Study Coordinator +5491155688183

Hospital Privado de Cordoba ( Site 2102); Completed

Cordoba, Argentina, X5016KEH

Brazil

Santa Casa de Misericordia de Belo Horizonte ( Site 0208); Recruiting

Belo Horizonte, Minas Gerais, Brazil, 30150-321

Contact: Study Coordinator +553132388849

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

Curitiba, Parana, Brazil, 80060-900

Contact: Study Coordinator +554133607938

Hospital Pequeno Principe ( Site 0200); Recruiting

Curitiba, Parana, Brazil, 80250-060

Contact: Study Coordinator +554191993340

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

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

Contact: Study Coordinator +5555981129912

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

Sao Paulo, Brazil, 04039-001

Contact: Study Coordinator +551150808592

Colombia

Hospital Pablo Tobon Uribe-Infectology pediatric ( Site 2166); Recruiting

Medellin, Antioquia, Colombia, 05034

Contact: Study Coordinator 3206716384

Fundacion Cardioinfantil Instituto de Cardiologia ( Site 2163); Recruiting

Bogota, Distrito Capital De Bogota, Colombia, 110131

Contact: Study Coordinator +573157734008

Fundacion Santa Fe de Bogota ( Site 2167); Recruiting

Bogotá, Distrito Capital De Bogota, Colombia, 110111

Contact: Study Coordinator +57 3115356577

Fundacion Valle del Lili ( Site 2161); Completed

Cali, Valle Del Cauca, Colombia, 760032

Centro Medico Imbanaco ( Site 2160); Recruiting

Cali, Valle Del Cauca, Colombia, 760042

Contact: Study Coordinator +572518500014091

Czechia

Fakultni Nemocnice Brno Bohunice ( Site 2000); Recruiting

Brno, Brno-mesto, Czechia, 613 00

Contact: Study Coordinator +420532234126

Fakultni nemocnice Plzen ( Site 2001); Completed

Plzen Lochotin, Plzensky Kraj, Czechia, 304 60

2. LF UK a FN Motol ( Site 2003); Recruiting

Praha 5, Czechia, 150 06

Contact: Study Coordinator +420224436420

Germany

Universitaetsklinikum Muenster ( Site 1400); Recruiting

Muenster, Nordrhein-Westfalen, Germany, 48149

Contact: Study Coordinator +492518352840

Universitaetsklinikum Hamburg Eppendorf ( Site 1402); Recruiting

Hamburg, Germany, 20246

Contact: Study Coordinator +4940741020400

Hungary

SZTE Szent-Gyorgyi Albert Klinikai Kozpont ( Site 2200); Recruiting

Szeged, Csongrad, Hungary, 6720

Contact: Study Coordinator +3662545330

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

Budapest, Hungary, 1094

Contact: Study Coordinator +3612151380

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

Budapest, Hungary, 1097

Malaysia

Sabah Womens & Childrens Hospital ( Site 3101); Recruiting

Kota Kinabalu, Sabah, Malaysia, 88996

Contact: Study Coordinator +6088522600

Hospital Kuala Lumpur ( Site 3100); Recruiting

Kuala Lumpur, Malaysia, 50300

Contact: Study Coordinator +60326155555

Mexico

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

Monterrey, Nuevo Leon, Mexico, 64400

Contact: Study Coordinator +528183486136

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

Monterrey, Nuevo Leon, Mexico, 64710

Instituto Nacional de Pediatria ( Site 0503); Recruiting

Mexico City, Mexico, 04530

Contact: Study Coordinator +525510840900

Hospital Infantil de Mexico Federico Gomez ( Site 0501); Recruiting

Mexico City, Mexico, 06720

Contact: Study Coordinator +525552289917

Norway

Haukeland universitetssykehus ( Site 1501); Recruiting

Bergen, Vestfold, Norway, 5053

Contact: Study Coordinator +4755975200

Oslo universitetssykehus ( Site 1500); Recruiting

Oslo, Norway, 0372

Contact: Study Coordinator +4723074593

Poland

Wojewodzki Szpital Obserwacyjno Zakazny ( Site 2404); Recruiting

Bydgoszcz, Kujawsko-pomorskie, Poland, 85-030

Contact: Study Coordinator +48523255605

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

Lodz, Lodzkie, Poland, 91-347

Contact: Study Coordinator +48422516104

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

Lomianki, Mazowieckie, Poland, 05-092

Contact: Study Coordinator +48227657153

Instytut Pomnik Centrum Zdrowia Dziecka ( Site 2406); Recruiting

Warszawa, Mazowieckie, Poland, 04-730

Contact: Study Coordinator +48228157384

Wojewodzki Specjalistyczny Szpital Dzieciecy ( Site 2410); Recruiting

Olsztyn, Warminsko-mazurskie, Poland, 10-561

Contact: Study Coordinator +48895393370

Portugal

Hospital de Braga ( Site 1600); Completed

Braga, Portugal, 4710-243

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

Lisboa, Portugal, 1169-045

Contact: Study Coordinator +351213126600

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

Lisboa, Portugal

Contact: Study Coordinator +351 21 722 9800

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

Porto, Portugal, 4200-072

Contact: Study Coordinator +351225084000

Romania

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

Cluj-Napoca, Cluj, Romania, 400348

Contact: Study Coordinator +40 364 131 238

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

Bucuresti, Romania, 021105

Contact: Study Coordinator +40212010980

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

Bucuresti, Romania, 030303

Contact: Study Coordinator +40723577388

Spitalul Clinic de Boli Infectioase Constanta ( Site 2504); Recruiting

Constanta, Romania, 900708

Contact: Study Coordinator +40241484521

South Africa

Phoenix Pharma Pty Ltd ( Site 2607); Recruiting

Port Elizabeth, Eastern Cape, South Africa, 6001

Contact: Study Coordinator +27413733832

Johese Clinical Research ( Site 2605); Completed

Centurion, Gauteng, South Africa, 1692

Chris Hani Baragwanath Academic Hospital ( Site 2602); Recruiting

Johannesburg, Gauteng, South Africa, 1860

Contact: Study Coordinator +27119330270

Molotlegi Street ( Site 2603); Recruiting

Pretoria, Gauteng, South Africa, 0208

Contact: Study Coordinator +27125215633

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

Cape Town, Western Cape, South Africa, 7700

Contact: Study Coordinator +27216585369

Spain

Hospital Universitario Sant Joan de Deu ( Site 1704); Recruiting

Esplugues de Llobregat, Barcelona, Spain, 08950

Contact: Study Coordinator +34915035900235

Hospital Infantil Universitario Nino Jesus ( Site 1701); Recruiting

Madrid, Spain, 28009

Contact: Study Coordinator +34915035900

Hospital Universitario La Paz ( Site 1703); Completed

Madrid, Spain, 28046

Hospital Universitario Virgen del Rocio ( Site 1705); Recruiting

Sevilla, Spain, 41013

Contact: Study Coordinator +34955012914

Sweden

ITCC Barnokologen Astrid Lindgrens Barnsjukhus NKS ( Site 1800); Recruiting

Stockholm, Stockholms Lan, Sweden, 17176

Contact: Study Coordinator +46722214431

Barncancercentrum ( Site 1801); Recruiting

Goteborg, Vastra Gotalands Lan, Sweden, 416 85

Contact: Study Coordinator +46313436082

United Kingdom

Southampton General Hospital ( Site 1900); Recruiting

Southampton, Worcestershire, United Kingdom, SO16 6YD

Contact: Study Coordinator +442381206883

Leeds Teaching Hospitals NHS Trust ( Site 1901); Recruiting

Leeds, United Kingdom, LS1 3EX

Contact: Study Coordinator +447824519571

Sponsors and Collaborators

Merck Sharp & Dohme Corp.

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme Corp.

More Information

• Responsible Party: Merck Sharp & Dohme Corp.
• ClinicalTrials.gov Identifier: NCT03182907
• Other Study ID Numbers: 6072-001; 2017-000070-11 ( EudraCT Number )
• First Posted: June 9, 2017
• Last Update Posted: October 7, 2021
• Last Verified: October 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Infections; Communicable Diseases; Clostridium Infections; Enterocolitis, Pseudomembranous; Disease Attributes; Pathologic Processes; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Enterocolitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases