AzTrials
AzTrials

Clostridium Difficile InfectionPhase 3MODIFY IIINCT03182907

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

A Phase 3 study testing Bezlotoxumab and Antibacterial drug treatment (ABD) in people with Clostridium Difficile Infection, run by Merck Sharp & Dohme LLC at 75 sites in 17 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 1 year to 17 years
Conditions the study is for
Clostridium Difficile Infection
What is being tested?
Bezlotoxumab and Antibacterial drug treatment (ABD)
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
148 participants
Where
75 sitesin 17 countries
Study dates
27 Mar 2018to 12 May 2022
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 year to 17 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

75 sites in 17 countries.

75 sites in 17 countries

United States21 sites

  • Children's Center for Digestive Healthcare ( Site 0052)

    Atlanta, Georgia, 30342

  • Children's Hospital - Colorado ( Site 0013)

    Aurora, Colorado, 80045

  • The Johns Hopkins Rubenstein Child Health Building ( Site 0034)

    Baltimore, Maryland, 21287

  • Our Lady of the Lake Hospital ( Site 0007)

    Baton Rouge, Louisiana, 70808

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

    Boston, Massachusetts, 02111

  • University of Chicago ( Site 0019)

    Chicago, Illinois, 60637

  • Cincinnati Children's Hospital Medical Center ( Site 0024)

    Cincinnati, Ohio, 45229

  • University Hospitals Cleveland Medical Center ( Site 0029)

    Cleveland, Ohio, 44106

  • Duke University Health System ( Site 0025)

    Durham, North Carolina, 27710

  • Children's Hospital - Los Angeles ( Site 0021)

    Los Angeles, California, 90027

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

    Memphis, Tennessee, 38105

  • Vanderbilt University Medical Center ( Site 0022)

    Nashville, Tennessee, 37232

  • Columbia University Medical Center/ MSCHONY ( Site 0042)

    New York, New York, 10032

  • Mayo Clinic - Rochester ( Site 0004)

    Rochester, Minnesota, 55905

  • Primary Children's Hospital ( Site 0001)

    Salt Lake City, Utah, 84113

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

    San Antonio, Texas, 78207

  • UCSF Medical Center ( Site 0049)

    San Francisco, California, 94158

  • Seattle Childrens Hospital ( Site 0028)

    Seattle, Washington, 98105

  • Washington University ( Site 0037)

    St Louis, Missouri, 63110

  • SUNY Upstate Medical Center, University Hospital ( Site 0027)

    Syracuse, New York, 13210

  • Montefiore Einstein Center ( Site 0041)

    The Bronx, New York, 10467

Other trials in United States

Brazil5 sites

  • Santa Casa de Misericordia de Belo Horizonte ( Site 0208)

    Belo Horizonte, Minas Gerais, 30150-321

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

    Curitiba, Paraná, 80060-900

  • Hospital Pequeno Principe ( Site 0200)

    Curitiba, Paraná, 80250-060

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

    Santa Maria, Rio Grande do Sul, 97105-900

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

    São Paulo, 04039-001

Other trials in Brazil

Colombia5 sites

  • Fundacion Santa Fe de Bogota ( Site 2167)

    Bogotá, Bogota D.C., 110111

  • Fundacion Cardioinfantil Instituto de Cardiologia ( Site 2163)

    Bogotá, Bogota D.C., 110131

  • Fundacion Valle del Lili ( Site 2161)

    Cali, Valle del Cauca Department, 760032

  • Centro Medico Imbanaco ( Site 2160)

    Cali, Valle del Cauca Department, 760042

  • Hospital Pablo Tobon Uribe-Infectology pediatric ( Site 2166)

    Medellín, Antioquia, 05034

Other trials in Colombia

Poland5 sites

  • Wojewodzki Szpital Obserwacyjno Zakazny ( Site 2404)

    Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-030

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

    Lodz, Łódź Voivodeship, 91-347

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

    Łomianki, Masovian Voivodeship, 05-092

  • Wojewodzki Specjalistyczny Szpital Dzieciecy ( Site 2410)

    Olsztyn, Warmian-Masurian Voivodeship, 10-561

  • Instytut Pomnik Centrum Zdrowia Dziecka ( Site 2406)

    Warsaw, Masovian Voivodeship, 04-730

Other trials in Poland

South Africa5 sites

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

    Cape Town, Western Cape, 7700

  • Johese Clinical Research ( Site 2605)

    Centurion, Gauteng, 1692

  • Chris Hani Baragwanath Academic Hospital ( Site 2602)

    Johannesburg, Gauteng, 1860

  • Phoenix Pharma Pty Ltd ( Site 2607)

    Port Elizabeth, Eastern Cape, 6001

  • Molotlegi Street ( Site 2603)

    Pretoria, Gauteng, 0208

Other trials in South Africa

Mexico4 sites

  • Instituto Nacional de Pediatria ( Site 0503)

    Mexico City, 04530

  • Hospital Infantil de Mexico Federico Gomez ( Site 0501)

    Mexico City, 06720

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

    Monterrey, Nuevo León, 64400

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

    Monterrey, Nuevo León, 64710

Other trials in Mexico

Portugal4 sites

  • Hospital de Braga ( Site 1600)

    Braga, 4710-243

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

    Lisbon, 1099-023

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

    Lisbon, 1169-045

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

    Porto, 4200-072

Other trials in Portugal

Romania4 sites

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

    Bucharest, 021105

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

    Bucharest, 030303

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

    Cluj-Napoca, Cluj, 400348

  • Spitalul Clinic de Boli Infectioase Constanta ( Site 2504)

    Constanța, 900708

Other trials in Romania

Spain4 sites

  • Hospital Universitario Sant Joan de Deu ( Site 1704)

    Esplugues de Llobregat, Barcelona, 08950

  • Hospital Infantil Universitario Nino Jesus ( Site 1701)

    Madrid, 28009

  • Hospital Universitario La Paz ( Site 1703)

    Madrid, 28046

  • Hospital Universitario Virgen del Rocio ( Site 1705)

    Seville, 41013

Other trials in Spain

Czechia3 sites

  • Fakultni Nemocnice Brno Bohunice ( Site 2000)

    Brno, Brno-mesto, 61300

  • Fakultni nemocnice Plzen ( Site 2001)

    Plzen Lochotin, Plzeň Region, 304 60

  • 2. LF UK a FN Motol ( Site 2003)

    Prague, 150 06

Other trials in Czechia

Hungary3 sites

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

    Budapest, 1094

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

    Budapest, 1097

  • SZTE Szent-Gyorgyi Albert Klinikai Kozpont ( Site 2200)

    Szeged, Csongrád megye, 6720

Other trials in Hungary

Argentina2 sites

  • Hospital Italiano de Buenos Aires. ( Site 2103)

    Caba, Buenos Aires, C1199ABB

  • Hospital Privado de Cordoba ( Site 2102)

    Córdoba, X5016KEH

Other trials in Argentina

Germany2 sites

  • Universitaetsklinikum Hamburg Eppendorf ( Site 1402)

    Hamburg, 20246

  • Universitaetsklinikum Muenster ( Site 1400)

    Münster, North Rhine-Westphalia, 48149

Other trials in Germany

Malaysia2 sites

  • Sabah Womens & Childrens Hospital ( Site 3101)

    Kota Kinabalu, Sabah, 88996

  • Hospital Kuala Lumpur ( Site 3100)

    Kuala Lumpur, 50300

Other trials in Malaysia

Norway2 sites

  • Haukeland universitetssykehus ( Site 1501)

    Bergen, Vestfold, 5053

  • Oslo universitetssykehus ( Site 1500)

    Oslo, 0372

Other trials in Norway

Sweden2 sites

  • Barncancercentrum ( Site 1801)

    Gothenburg, Västra Götaland County, 416 85

  • ITCC Barnokologen Astrid Lindgrens Barnsjukhus NKS ( Site 1800)

    Stockholm, Stockholm County, 17176

Other trials in Sweden

United Kingdom2 sites

  • Leeds Teaching Hospitals NHS Trust ( Site 1901)

    Leeds, LS1 3EX

  • Southampton General Hospital ( Site 1900)

    Southampton, Worcestershire, SO16 6YD

Other trials in United Kingdom

About this study

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)

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.

Read the detailed description

Historical adult pharmacokinetic data is from NCT01241552 and NCT01513239.

Being tested
Bezlotoxumab, Placebo, Antibacterial drug treatment (ABD)
Medical subject headings
Clostridium Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BezlotoxumabBiological

    Also called MK-6072

    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.

  • PlaceboDrug

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

  • 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.

Study groups in NCT03182907
Study groupRoleWhat they receive
BezlotoxumabExperimentalParticipants 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.
Receives: Biological: Bezlotoxumab; Drug: Antibacterial drug treatment (ABD)
PlaceboPlacebo comparatorParticipants 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.
Receives: Drug: Placebo; Drug: Antibacterial drug treatment (ABD)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

  2. 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.

    Measured: Up to approximately 12 weeks

  3. 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.

    Measured: Up to approximately 12 weeks

Secondary outcomes (6)

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

    CDI recurrence was defined as diarrhea recurrence (new episode of diarrhea after initial clinical response [ICR] as defined by a change in normal bowel habits for ≥2 days with either watery diarrhea or at least 6 unformed bowel movements [UBMs] within 48-hours) associated with a positive stool test for C. difficile toxin, and for which the participant, in the investigator's opinion, requires and receives ABD treatment for CDI. Per protocol, percentage of participants who had a CDI recurrence in the bezlotoxumab and placebo groups were reported.

    Measured: Up to approximately 12 Weeks

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

    SCR was defined as the ICR of baseline CDI episode (improvement in number and character of bowel movements and doesn't require further CDI therapy within 2 days after completion of up to 21 days of ABD treatment for CDI) and no CDI recurrence (diarrhea recurrence associated with a positive stool test for C. difficile toxin, and for which the participant, in investigator's opinion, requires and receives ABD for CDI). Per protocol, percentage of participants who had a SCR in bezlotoxumab and placebo groups were presented.

    Measured: Up to approximately 12 Weeks

  3. Percentage of High-Risk Participants Who Experienced a CDI Recurrence

    CDI recurrence was defined as diarrhea recurrence (new diarrhea episode after ICR defined by change in normal bowel habits for ≥2 days with watery diarrhea or at least 6 UBMs within 48-hours) with positive stool test for C. difficile toxin for which participant, in investigator's opinion, requires and receives ABD for CDI. High-risk was meeting ≥1 criteria at/before randomization: a) was immunocompromised b) had ≥1 CDI episode prior to baseline episode c) had severe CDI baseline episode d) had C. difficile ribotype027 in stool at baseline CDI episode e) received ≥1 systemic ABD known to increase CDI risk. Per protocol, percentage of high-risk participants who experienced a CDI recurrence in the bezlotoxumab and placebo groups were presented.

    Measured: Up to approximately 12 Weeks

  4. Percentage of High-Risk Participants Who Experienced a SCR

    SCR was ICR of baseline CDI episode (improvement in number and character of bowel movements and doesn't require further CDI therapy within 2 days after completion of up to 21 days of ABD for CDI) and no CDI recurrence (diarrhea recurrence with positive stool test for C. difficile toxin, for which participant, in investigator's opinion, requires and receives ABD for CDI). High-risk was meeting ≥1 criteria: a) was immunocompromised b) had ≥1 episodes of CDI prior to baseline episode c) had severe CDI baseline episode d) had C. difficile ribotype027 in stool at baseline CDI episode e) received ≥1 systemic ABD known to increase CDI risk. Per protocol, percentage of high-risk participants who had SCR in bezlotoxumab and placebo groups were presented.

    Measured: Up to approximately 12 Weeks

  5. Percentage of Participants Who Experienced One or More Infusion Related Reaction

    Infusion related reaction included events meeting any of the 3 criteria: 1) acute onset of an illness involving skin, mucosal tissue, or both and at least 1 of the following: respiratory compromise, reduced blood pressure (BP) or associated symptoms of end-organ dysfunction 2) two or more of the following after onset of study infusion: involving skin-mucosal tissue, respiratory compromise, reduced BP or associated symptoms, or persistent gastrointestinal symptoms 3) reduced BP after onset of infusion or >30% decrease in systolic BP from baseline. Per protocol, percentage of participants experiencing 1 or more infusion-related reactions within 24 hours following the start of study medication infusion were reported.

    Measured: Up to approximately 24 hours after infusion on Day 1

  6. Percentage of Participants Who Had Positive Antibodies to Bezlotoxumab

    Blood samples were collected to determine antibodies to bezlotoxumab. Per protocol, percentage of participants with treatment-emergent positive antibodies to bezlotoxumab following single infusion of bezlotoxumab were reported for each age cohort.

    Measured: Up to approximately 12 Weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Jun 2017
  2. Study start27 Mar 2018
  3. Primary completion12 May 2022
  4. Study completion12 May 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
148 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03182907
Sponsor's protocol ID
6072-001
Other IDs
MK-6072-001, 2017-000070-11, 2017
Acronym
MODIFY III
Status last verified
Jul 2023
First submitted
8 Jun 2017
Last updated
27 Jul 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

  • 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.

    PubMed 37389891

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Bezlotoxumab and Antibacterial drug treatment (ABD) in people with Clostridium Difficile Infection, run by Merck Sharp & Dohme LLC at 75 sites in 17 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 75 sites in United States, Brazil, Colombia, Poland, South Africa and 12 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Jun 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Area Under the Concentration-Time Curve of Bezlotoxumab From Time 0 to Infinity (AUC0-inf) (time frame: Day 1 (2 hours postdose), Days 10, 29, 57, and 85). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03182907, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jul 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in