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| ID | Type | Description | Link |
|---|---|---|---|
| MK-6072-001 | Other Identifier | Merck | |
| 2017-000070-11 | EudraCT Number |
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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.
Historical adult pharmacokinetic data is from NCT01241552 and NCT01513239.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital - Los Angeles ( Site 0021) | Los Angeles | California | 90027 | United States | ||
| UCSF Medical Center ( Site 0049) |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37389891 | Result | 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. |
| Label | URL |
|---|---|
| Merck Clinical Trial Information | View source |
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148 participants were randomized in the study of which 143 participants received study intervention and were used for safety analysis.
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| ID | Title | Description |
|---|---|---|
| FG000 | Bezlotoxumab | Participants received 10 mg of bezlotoxumab per kg body weight via a single 60-minute (±10 minutes) intravenous (IV) infusion on Day 1. Additionally, participants received background ABD for 10-21 days per institutional guidelines, at the investigator's discretion. |
| FG001 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 7, 2019 |
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|
| Placebo | Drug | 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. |
|
| Up to approximately 12 Weeks |
| 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. | Up to approximately 12 Weeks |
| 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. | Up to approximately 12 Weeks |
| 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. | Up to approximately 12 Weeks |
| 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. | Up to approximately 24 hours after infusion on Day 1 |
| 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. | Up to approximately 12 Weeks |
| San Francisco |
| California |
| 94158 |
| United States |
| Children's Hospital - Colorado ( Site 0013) | Aurora | Colorado | 80045 | United States |
| Children's Center for Digestive Healthcare ( Site 0052) | Atlanta | Georgia | 30342 | United States |
| University of Chicago ( Site 0019) | Chicago | Illinois | 60637 | United States |
| Our Lady of the Lake Hospital ( Site 0007) | Baton Rouge | Louisiana | 70808 | United States |
| The Johns Hopkins Rubenstein Child Health Building ( Site 0034) | Baltimore | Maryland | 21287 | United States |
| Tufts Medical Center-Floating Hospital for Children ( Site 0046) | Boston | Massachusetts | 02111 | United States |
| Mayo Clinic - Rochester ( Site 0004) | Rochester | Minnesota | 55905 | United States |
| Washington University ( Site 0037) | St Louis | Missouri | 63110 | United States |
| Columbia University Medical Center/ MSCHONY ( Site 0042) | New York | New York | 10032 | United States |
| SUNY Upstate Medical Center, University Hospital ( Site 0027) | Syracuse | New York | 13210 | United States |
| Montefiore Einstein Center ( Site 0041) | The Bronx | New York | 10467 | United States |
| Duke University Health System ( Site 0025) | Durham | North Carolina | 27710 | United States |
| Cincinnati Children's Hospital Medical Center ( Site 0024) | Cincinnati | Ohio | 45229 | United States |
| University Hospitals Cleveland Medical Center ( Site 0029) | Cleveland | Ohio | 44106 | United States |
| St. Jude Children's Research Hospital ( Site 0050) | Memphis | Tennessee | 38105 | United States |
| Vanderbilt University Medical Center ( Site 0022) | Nashville | Tennessee | 37232 | United States |
| The Children's Hospital of San Antonio ( Site 0009) | San Antonio | Texas | 78207 | United States |
| Primary Children's Hospital ( Site 0001) | Salt Lake City | Utah | 84113 | United States |
| Seattle Childrens Hospital ( Site 0028) | Seattle | Washington | 98105 | United States |
| Hospital Italiano de Buenos Aires. ( Site 2103) | Caba | Buenos Aires | C1199ABB | Argentina |
| Hospital Privado de Cordoba ( Site 2102) | Córdoba | X5016KEH | Argentina |
| Santa Casa de Misericordia de Belo Horizonte ( Site 0208) | Belo Horizonte | Minas Gerais | 30150-321 | Brazil |
| Hospital de Clinicas da Universidade Federal do Parana ( Site 0203) | Curitiba | Paraná | 80060-900 | Brazil |
| Hospital Pequeno Principe ( Site 0200) | Curitiba | Paraná | 80250-060 | Brazil |
| Hospital Universitario da Universidade Federal de Santa Maria ( Site 0209) | Santa Maria | Rio Grande do Sul | 97105-900 | Brazil |
| Instituto de Oncologia Pediatrica - GRAACC - Unifesp ( Site 0205) | São Paulo | 04039-001 | Brazil |
| Hospital Pablo Tobon Uribe-Infectology pediatric ( Site 2166) | Medellín | Antioquia | 05034 | Colombia |
| Fundacion Santa Fe de Bogota ( Site 2167) | Bogotá | Bogota D.C. | 110111 | Colombia |
| Fundacion Cardioinfantil Instituto de Cardiologia ( Site 2163) | Bogotá | Bogota D.C. | 110131 | Colombia |
| Fundacion Valle del Lili ( Site 2161) | Cali | Valle del Cauca Department | 760032 | Colombia |
| Centro Medico Imbanaco ( Site 2160) | Cali | Valle del Cauca Department | 760042 | Colombia |
| Fakultni Nemocnice Brno Bohunice ( Site 2000) | Brno | Brno-mesto | 61300 | Czechia |
| Fakultni nemocnice Plzen ( Site 2001) | Plzen Lochotin | Plzeň Region | 304 60 | Czechia |
| 2. LF UK a FN Motol ( Site 2003) | Prague | 150 06 | Czechia |
| Universitaetsklinikum Muenster ( Site 1400) | Münster | North Rhine-Westphalia | 48149 | Germany |
| Universitaetsklinikum Hamburg Eppendorf ( Site 1402) | Hamburg | 20246 | Germany |
| SZTE Szent-Gyorgyi Albert Klinikai Kozpont ( Site 2200) | Szeged | Csongrád megye | 6720 | Hungary |
| Semmelweis University-II.sz. Gyermekgyógyászati Klinika ( Site 2201) | Budapest | 1094 | Hungary |
| Del-pesti Centrumkorhaz Orszagos Hematologiai es Infektologiai Intezet ( Site 2202) | Budapest | 1097 | Hungary |
| Sabah Womens & Childrens Hospital ( Site 3101) | Kota Kinabalu | Sabah | 88996 | Malaysia |
| Hospital Kuala Lumpur ( Site 3100) | Kuala Lumpur | 50300 | Malaysia |
| Hospital Universitario "Dr. Jose Eleuterio Gonzalez" ( Site 0508) | Monterrey | Nuevo León | 64400 | Mexico |
| Instituto Tecnologico y de Estudios Superiores de Monterrey ( Site 0502) | Monterrey | Nuevo León | 64710 | Mexico |
| Instituto Nacional de Pediatria ( Site 0503) | Mexico City | 04530 | Mexico |
| Hospital Infantil de Mexico Federico Gomez ( Site 0501) | Mexico City | 06720 | Mexico |
| Haukeland universitetssykehus ( Site 1501) | Bergen | Vestfold | 5053 | Norway |
| Oslo universitetssykehus ( Site 1500) | Oslo | 0372 | Norway |
| Wojewodzki Szpital Obserwacyjno Zakazny ( Site 2404) | Bydgoszcz | Kuyavian-Pomeranian Voivodeship | 85-030 | Poland |
| Instytut Pomnik Centrum Zdrowia Dziecka ( Site 2406) | Warsaw | Masovian Voivodeship | 04-730 | Poland |
| SPZOZ im. Dzieci Warszawy w Dziekanowie Lesnym ( Site 2405) | Łomianki | Masovian Voivodeship | 05-092 | Poland |
| Wojewodzki Specjalistyczny Szpital Dzieciecy ( Site 2410) | Olsztyn | Warmian-Masurian Voivodeship | 10-561 | Poland |
| Wojewodzki Specjalistyczny Szpital im. dr W. Bieganskiego w Lodzi ( Site 2400) | Lodz | Łódź Voivodeship | 91-347 | Poland |
| Hospital de Braga ( Site 1600) | Braga | 4710-243 | Portugal |
| Inst. Portugues de Oncologia de Lisboa Francisco Gentil EPE ( Site 1605) | Lisbon | 1099-023 | Portugal |
| Centro Hospitalar de Lisboa Central EPE. Hospital D. Estefania ( Site 1601) | Lisbon | 1169-045 | Portugal |
| Instituto Portugues de Oncologia Do Porto Francisco Gentil E.P.E. ( Site 1603) | Porto | 4200-072 | Portugal |
| Spitalul Clinic de Boli Infectioase Cluj-Napoca ( Site 2502) | Cluj-Napoca | Cluj | 400348 | Romania |
| Institutul National de Boli Infectioase Prof. Dr. Matei Bals ( Site 2501) | Bucharest | 021105 | Romania |
| Spitalul Clinic de Boli Infectioase si Tropicale Dr. Victor Babes ( Site 2500) | Bucharest | 030303 | Romania |
| Spitalul Clinic de Boli Infectioase Constanta ( Site 2504) | Constanța | 900708 | Romania |
| Phoenix Pharma Pty Ltd ( Site 2607) | Port Elizabeth | Eastern Cape | 6001 | South Africa |
| Johese Clinical Research ( Site 2605) | Centurion | Gauteng | 1692 | South Africa |
| Chris Hani Baragwanath Academic Hospital ( Site 2602) | Johannesburg | Gauteng | 1860 | South Africa |
| Molotlegi Street ( Site 2603) | Pretoria | Gauteng | 0208 | South Africa |
| Red Cross War Memorial Children's Hospital ( Site 2601) | Cape Town | Western Cape | 7700 | South Africa |
| Hospital Universitario Sant Joan de Deu ( Site 1704) | Esplugues de Llobregat | Barcelona | 08950 | Spain |
| Hospital Infantil Universitario Nino Jesus ( Site 1701) | Madrid | 28009 | Spain |
| Hospital Universitario La Paz ( Site 1703) | Madrid | 28046 | Spain |
| Hospital Universitario Virgen del Rocio ( Site 1705) | Seville | 41013 | Spain |
| ITCC Barnokologen Astrid Lindgrens Barnsjukhus NKS ( Site 1800) | Stockholm | Stockholm County | 17176 | Sweden |
| Barncancercentrum ( Site 1801) | Gothenburg | Västra Götaland County | 416 85 | Sweden |
| Southampton General Hospital ( Site 1900) | Southampton | Worcestershire | SO16 6YD | United Kingdom |
| Leeds Teaching Hospitals NHS Trust ( Site 1901) | Leeds | LS1 3EX | United Kingdom |
| Placebo |
Participants received 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 received background ABD for 10-21 days per institutional guidelines, at the investigator's discretion. |
| Treated |
|
| COMPLETED |
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| NOT COMPLETED |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Bezlotoxumab | Participants received 10 mg of bezlotoxumab per kg body weight via a single 60-minute (±10 minutes) intravenous (IV) infusion on Day 1. Additionally, participants received background ABD for 10-21 days per institutional guidelines, at the investigator's discretion. |
| BG001 | Placebo | Participants received 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 received background ABD for 10-21 days per institutional guidelines, at the investigator's discretion. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | The analysis population included all participants who received bezlotoxumab, had at least 4 postdose AUC0-inf samples and complied with the protocol. | Posted | Geometric Mean | 95% Confidence Interval | hr*ug/mL | Day 1 (2 hours postdose), Days 10, 29, 57, and 85 |
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| Primary | 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. | The analysis population included all participants who received study intervention. | Posted | Number | Percentage of participants | Up to approximately 12 weeks |
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| Primary | 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. | The analysis population included all participants who received study intervention. | Posted | Number | Percentage of participants | Up to approximately 12 weeks |
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| Secondary | 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. | The analysis population included all participants who received any amount of study intervention, had positive local stool for C. difficile toxin, were taking protocol-defined ABD treatment for CDI on the day of infusion, and achieved an ICR of baseline CDI. | Posted | Number | Percentage of participants | Up to approximately 12 Weeks |
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| Secondary | 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. | The analysis population included all participants who received any amount of study intervention, had positive local stool for C. difficile toxin, and were taking protocol-defined ABD treatment for CDI on the day of infusion. | Posted | Number | Percentage of participants | Up to approximately 12 Weeks |
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| Secondary | 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. | The analysis population included all participants who received study intervention, had positive local stool for C. difficile toxin, were taking ABD for CDI on infusion day, achieved ICR of baseline CDI, and were at high-risk of CDI recurrence. | Posted | Number | Percentage of participants | Up to approximately 12 Weeks |
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| Secondary | 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. | The analysis population included all participants who received study intervention, had positive local stool for C. difficile toxin, were taking protocol-defined ABD for CDI on the day of infusion, and were at high risk of CDI recurrence. | Posted | Number | Percentage of participants | Up to approximately 12 Weeks |
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| Secondary | 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. | The analysis population included all participants who received study intervention. | Posted | Number | Percentage of participants | Up to approximately 24 hours after infusion on Day 1 |
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| Secondary | 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. | The analysis population included all participants who received any amount of bezlotoxumab, had a positive local stool for C. difficile toxin, were taking protocol-defined ABD drug treatment for CDI on the day of infusion, and achieved an ICR of baseline CDI. | Posted | Number | Percentage of participants | Up to approximately 12 Weeks |
|
Up to approximately 14 months
All cause mortality was reported on all randomized participants and non-serious and serious AEs were reported on all participants who received study intervention.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Bezlotoxumab | Participants received 10 mg of bezlotoxumab per kg body weight via a single 60-minute (±10 minutes) intravenous (IV) infusion on Day 1. Additionally, participants received background ABD for 10-21 days per institutional guidelines, at the investigator's discretion. | 6 | 111 | 57 | 107 | 65 | 107 |
| EG001 | Placebo | Participants received 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 received background ABD for 10-21 days per institutional guidelines, at the investigator's discretion. | 1 | 37 | 29 | 36 | 28 | 36 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Agranulocytosis | Blood and lymphatic system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Bone marrow failure | Blood and lymphatic system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Leukocytosis | Blood and lymphatic system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Anal inflammation | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Intussusception | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Pancreatitis | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Biliary-bronchial fistula | Hepatobiliary disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Cholecystitis | Hepatobiliary disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Drug hypersensitivity | Immune system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Graft versus host disease | Immune system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Acinetobacter sepsis | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Adenovirus infection | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Bacteraemia | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Bacterial sepsis | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Candida sepsis | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Clostridium difficile colitis | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Clostridium difficile infection | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Coronavirus infection | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Cytomegalovirus infection | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Enterobacter bacteraemia | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Escherichia bacteraemia | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Fungal sepsis | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Gastroenteritis sapovirus | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Klebsiella bacteraemia | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Neutropenic infection | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Neutropenic sepsis | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Nosocomial infection | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Otitis media acute | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Pharyngitis streptococcal | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Pharyngotonsillitis | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Pneumonia aspiration | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Pneumonia fungal | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Pseudomonal bacteraemia | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Pseudomonal sepsis | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Respiratory syncytial virus infection | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Septic shock | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Serratia bacteraemia | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Soft tissue infection | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Staphylococcal bacteraemia | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Staphylococcal sepsis | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Streptococcal bacteraemia | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Urosepsis | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Viral infection | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Vulval cellulitis | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Allergic transfusion reaction | Injury, poisoning and procedural complications | MedDRA 25.0 | Systematic Assessment |
| |
| C-reactive protein increased | Investigations | MedDRA 25.0 | Systematic Assessment |
| |
| SARS-CoV-2 test positive | Investigations | MedDRA 25.0 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Myopathy | Musculoskeletal and connective tissue disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Acute myeloid leukaemia | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 25.0 | Systematic Assessment |
| |
| Leukaemia | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 25.0 | Systematic Assessment |
| |
| Neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 25.0 | Systematic Assessment |
| |
| Neuroblastoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 25.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Loss of consciousness | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Neurotoxicity | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Nystagmus | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Acute respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Respiratory tract oedema | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Venoocclusive disease | Vascular disorders | MedDRA 25.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Bacteraemia | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Oral herpes | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Transfusion reaction | Injury, poisoning and procedural complications | MedDRA 25.0 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 25.0 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 25.0 | Systematic Assessment |
| |
| C-reactive protein increased | Investigations | MedDRA 25.0 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Vancomycin infusion reaction | Skin and subcutaneous tissue disorders | MedDRA 25.0 | Systematic Assessment |
|
The SPONSOR must have the opportunity to review all proposed abstracts and manuscripts regarding this study prior to submission for publication. This will allow the SPONSOR to protect the proprietary information prior to submission.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme LLC | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| Apr 6, 2023 |
| Prot_SAP_000.pdf |
Not provided
| ID | Term |
|---|---|
| D003015 | Clostridium Infections |
| ID | Term |
|---|---|
| D016908 | Gram-Positive Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
Not provided
Not provided
| ID | Term |
|---|---|
| C000613978 | bezlotoxumab |
Not provided
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
| GMR |
| 0.82 |
| 2-Sided |
| 90 |
| 0.75 |
| 0.89 |
GMR was calculated as the Cohort 2 GM AUC0-inf / Adult GM AUC0-inf. |
| Other |
The AUC0-inf of bezlotoxumab in Cohort 2 was compared to the AUC0-inf of bezlotoxumab in adults using an analysis of variance (ANOVA) model. The comparison adult PK dataset used was based on participants from 2 adult trials (NCT01241552 and NCT01513239) as a historical control. |
| Units | Counts |
|---|---|
| Participants |
|
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
|
|
|
|
|
|
Participants received 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 received background ABD for 10-21 days per institutional guidelines, at the investigator's discretion.
|
|
|
|
|
|
|
|
| Units | Counts |
|---|---|
| Participants |
|
|