A Study of Safety and Efficacy of MK-1986 (Tedizolid Phosphate) and Comparator in Participants From Birth to Less Than 12 Years of Age With Acute Bacterial Skin and Skin Structure Infections (MK-1986-018)

A Phase III Randomized, Active-comparator-Controlled Clinical Trial to Study the Safety and Efficacy of MK-1986 (Tedizolid Phosphate) and Comparator, in Subjects From Birth to Less Than 12 Years of Age With Acute Bacterial Skin and Skin Structure Infections (ABSSSI)

This study will evaluate the safety, tolerability, and efficacy of tedizolid phosphate (MK-1986) compared with comparator antibacterial agent in participants from birth to less than 12 years of age with acute bacterial skin and skin structure infections (ABSSSI).

Study Overview

• Status: Completed
• Conditions: Acute Bacterial Skin and Skin Structure Infections
• Intervention / Treatment: Drug: Tedizolid phosphate; Drug: Comparator

Detailed Description

Participants will be randomized (3:1) to receive tedizolid phosphate at a weight-based dose ≤200 mg/day, intravenous (IV) and/or oral suspension for 6 to 10 days, or comparator IV and/or oral per local standard of care for 10 to 14 days. The switch from IV to oral administration can be made at any time based on 1) no worsening of the primary skin lesion, 2) last temperature <37.7 °C, and 3) primary acute bacterial skin and skin structure infection (ABSSSI) site has not worsened and at least 1 site has improved from Baseline. The potential 4-day treatment extension will be based on clinical need as judged by the investigator, considering the following criteria: 1) ≥40% reduction in primary lesion size, 2) reduction in pain, and 3) no new signs and symptoms and no complications attributable to ABSSSI compared with Baseline.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Sao Paulo, Brazil, 04321-120
    • Instituto D'Or de Pesquisa e Ensino (IDOR)-Hospital São Luiz Jabaquara ( Site 0283)
  • Parana
    • Curitiba, Parana, Brazil, 80250-060
      • Hospital Pequeno Principe ( Site 0276)
  • Pernambuco
    • Recife, Pernambuco, Brazil, 50070-902
      • Inst de Medicina Integral Professor Fernando Figueira- IMIP ( Site 0277)
  • Rio Grande Do Norte
    • Natal, Rio Grande Do Norte, Brazil, 59025-050
      • Centro de Estudos e Pesquisa em Molestias Infecciosas - CPCL-CENTRO DE ESTUDOS E PESQUISAS EM MOLES
• Bulgaria
  • Burgas, Bulgaria, 8127
    • UMHAT Deva Maria ( Site 0333)
  • Montana, Bulgaria, 3400
    • MHAT City Clinic Sv. Georgi EOOD ( Site 0334)
  • Montana, Bulgaria, 3400
    • MHAT Dr. Stamen Iliev AD ( Site 0339)
  • Pleven, Bulgaria, 5800
    • UMHAT Dr. Georgi Stranski EAD ( Site 0330)
  • Plovdiv, Bulgaria, 4002
    • UMHAT Sv. Georgi ( Site 0332)
  • Ruse, Bulgaria, 7000
    • MBAL Medica Ruse EOOD ( Site 0336)
  • Ruse, Bulgaria, 7002
    • UMHAT Kanev AD ( Site 0337)
  • Sofia, Bulgaria, 1606
    • UMHATEM. N.I.Pirogov. EAD ( Site 0331)
  • Montana
    • Lom, Montana, Bulgaria, 3600
      • MHAT Sv. Nikolay Chudotvorets EOOD ( Site 0338)
• Georgia
  • Tbilisi, Georgia, 0159
    • JSC Evex Hospital ( Site 0602)
  • Tbilisi, Georgia, 0159
    • JSC Evex Hospitals ( Site 0603)
  • Ajaria
    • Batumi, Ajaria, Georgia, 6010
      • JSC Evex Hospitals. ( Site 0601)
  • Tbilisi
    • Tiblisi, Tbilisi, Georgia, 0159
      • Tbilisi State Medical University G. Zhvania Pediatric Academic Clinic ( Site 0600)
• Germany
  • Bayern
    • München, Bayern, Germany, 80337
      • Haunersches Kinderspital ( Site 0480)
• Guatemala
  • Guatemala, Guatemala, 01001
    • Clinica Privada ( Site 0551)
  • Guatemala, Guatemala, 01009
    • Private Practice Mario Melgar ( Site 0552)
  • Guatemala, Guatemala, 01010
    • Private Practice Dra. Manrique ( Site 0553)
• Latvia
  • Daugavpils, Latvia, 5417
    • Daugavpils Regional Hospital ( Site 0651)
  • Liepaja, Latvia, 3414
    • Liepaja Regional Hospital ( Site 0652)
• Lithuania
  • Kaunas, Lithuania, 50161
    • Hospital of Lithuanian University of Health Sciences Kaunas ( Site 0701)
  • Klaipeda, Lithuania, 92140
    • Klaipedos Vaiku Ligonine ( Site 0700)
  • Vilnius, Lithuania, 08406
    • Vaiku ligonine VsI VUL Santaros kliniku filialas ( Site 0702)
• Mexico
  • Aguascalientes, Mexico, 20259
    • Centenario Hospital Miguel Hidalgo-Pediatrics Department ( Site 0239)
  • Distrito Federal
    • Mexico City, Distrito Federal, Mexico, 04530
      • Instituto Nacional de Pediatria ( Site 0231)
    • Mexico City, Distrito Federal, Mexico, 06720
      • Hospital Infantil de Mexico Federico Gomez ( Site 0227)
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44280
      • Hospital Civil Fray Antonio Alcalde-pediatrics infectious diseases ( Site 0230)
  • Nuevo Leon
    • Gral Escobedo, Nuevo Leon, Mexico, 64060
      • CHRISTUS - LATAM HUB CENTER OF EXCELLENCE AND INNOVATION S.C. ( Site 0241)
• Poland
  • Kujawsko-pomorskie
    • Bydgoszcz, Kujawsko-pomorskie, Poland, 85-030
      • Wojewodzki Szpital Obserwacyjno Zakazny ( Site 0429)
  • Lodzkie
    • Lodz, Lodzkie, Poland, 91-347
      • Wojewodzki Szpital Specjalistyczny im. dr. Wladyslawa Bieganskiego ( Site 0427)
  • Mazowieckie
    • Lomianki, Mazowieckie, Poland, 05-092
      • SZPZOZ im. Dzieci Warszawy w Dziekanowie Lesnym ( Site 0431)
• Russian Federation
  • Novosibirskaya Oblast
    • Novosibirsk, Novosibirskaya Oblast, Russian Federation, 630007
      • City Childrens Clinical Emergency Hospital ( Site 0507)
  • Smolenskaya Oblast
    • Smolensk, Smolenskaya Oblast, Russian Federation, 214018
      • Smolensk Regional Clinical Hospital ( Site 0511)
  • Tatarstan, Respublika
    • Kazan, Tatarstan, Respublika, Russian Federation, 420138
      • Children s Republican Clinical Hospital ( Site 0512)
• South Africa
  • Gauteng
    • Pretoria, Gauteng, South Africa, 0084
      • Emmed Research Incorporating ( Site 0377)
    • Pretoria, Gauteng, South Africa, 0152
      • Setshaba Research Centre ( Site 0378)
  • Kwazulu-Natal
    • Durban, Kwazulu-Natal, South Africa, 4013
      • Enhancing Care Foundation-DICRS ( Site 0381)
• Turkey
  • Adana, Turkey, 01330
    • Cukurova Uni Tip Fak Cocuk Saglıgı ve Hasta ABD ( Site 0353)
  • Ankara, Turkey, 06230
    • Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 0351)
  • Ankara, Turkey, 06800
    • Ankara City Hospital-Infectious Disease and Clinical Microbiology ( Site 0359)
  • Eskisehir, Turkey, 26480
    • Osmangazi UTF ( Site 0357)
  • Istanbul, Turkey, 34093
    • Istanbul Universitesi Istanbul Tip Fakultesi ( Site 0355)
  • Istanbul, Turkey, 34371
    • Sisli Hamide Etfal Egitim ve Arastirma Hastanesi ( Site 0358)
  • Izmir, Turkey, 35040
    • Ege UTF ( Site 0356)
• Ukraine
  • Dnipropetrovska Oblast
    • Dnipro, Dnipropetrovska Oblast, Ukraine, 49100
      • Dnipropetrovsk Oblast Children's Clinical Hospital ( Site 0868)
    • Dnipro, Dnipropetrovska Oblast, Ukraine, 49100
      • SI Dnipropetrovsk Regional Children Clinical Hospital DOR ( Site 0863)
  • Ivano-Frankivska Oblast
    • Ivano-Frankivsk, Ivano-Frankivska Oblast, Ukraine, 76014
      • Ivano-Frankivsk Regional Children Clinical Hospital ( Site 0865)
• United States
  • California
    • San Diego, California, United States, 92123
      • Rady Children's Hospital-San Diego ( Site 0118)
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital of Chicago ( Site 0129)
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Children's Hospital of Michigan ( Site 0100)
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital ( Site 0108)
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • St. Louis Children's Hospital ( Site 0127)
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Medical Center ( Site 0124)
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine - Texas Children's Hospital ( Site 0107)
  • Virginia
    • Richmond, Virginia, United States, 23219
      • Children's Hospital of Richmond at VCU ( Site 0123)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 11 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Has a parent/legally acceptable representative who is able to give documented informed consent
• Has ABSSSI, defined as ≥1 of the following: 1) cellulitis/erysipelas, 2) major cutaneous abscess, or 3) wound infection
• Local symptoms of ABSSSI that started within 14 days before study start
• Suspected or documented Gram-positive bacterial infection
• Body weight ≥3.2 kg

Exclusion Criteria:

• Uncomplicated skin and skin structure infection
• ABSSSI due to or associated with disallowed etiology per protocol
• Received antibacterial therapy for treatment of the current episode of ABSSSI except 1) <48 hours of antibacterial therapy with a short-acting antibacterial drug, or 2) response is considered to be failure (no improvement in signs and symptoms) after at least 48 hours of therapy
• Known bacteremia, severe sepsis, or septic shock
• Significant or life-threatening condition, disease, or organ system condition
• Recent history of opportunistic infections where the underlying cause of the infection is still active, or is suspected to be at risk of opportunistic infection with unusual pathogens
• Received or is receiving treatment for active tuberculosis within 1 month of study start
• Known or suspected severe neutropenia
• Human immunodeficiency virus (HIV) positive and has Cluster of Differentiation (CD) 4 cell count <15% (HIV testing is not required for eligibility)
• Renal impairment that requires renal filtration
• Severe hepatic impairment
• Cardiac or electrocardiogram (ECG) finding that would limit participation in the study
• Received an investigational medicinal product (not approved) within 30 days before study start
• Investigational device present or removed within 30 days before study start
• Previously treated with tedizolid phosphate
• Contraindication, including hypersensitivity to tedizolid phosphate, other oxazolidinones, or any component in the formulation
• Contraindication, including hypersensitivity to all available comparator drugs
• Wound infection and history of hypersensitivity to aztreonam adjunctive therapy or metronidazole adjunctive therapy, if adjunctive therapy is required
• Needs oral administration of methotrexate, topotecan, irinotecan, or rosuvastatin, during administration of oral study drug (administration during the follow-up period, ie, after the EOT visit, is allowed, as is administration during treatment with IV drug)
• Female who is pregnant or nursing or is of childbearing potential and not abstinent; or male who is not abstinent
• Use of monoamine oxidase inhibitors, tricyclic antidepressants, buspirone, selective serotonin reuptake inhibitors, or serotonin 5-hydroxytryptamine receptor agonists (triptans)
• Identified as having used illicit drugs (urine drug screening not required for entry)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: Tedizolid phosphate 6 to <12 Years; Participants will receive tedizolid phosphate once-daily single 200-mg dose (body weight ≥50 kg) or twice-daily 2-mg/kg doses (body weight 30 kg to <50 kg); or twice-daily 2.5-mg/kg doses (body weight 3.2 kg to <30 kg), by IV and/or oral suspension for 6 to 10 days.	Drug: Tedizolid phosphate; Tedizolid phosphate IV solution or oral suspension; Other Names: TR-701 FA; MK-1986
Active Comparator: Cohort 1 Comparator: 6 to <12 Years; Participants will receive comparator IV and/or oral per local standard of care for 10 to 14 days	Drug: Comparator; Vancomycin IV, linezolid IV or oral (outside European Union only), clindamycin IV or oral, flucloxacillin IV or oral, cefazolin IV, or cephalexin oral provided locally by the trial site and administered per local standard of care
Experimental: Cohort 2: Tedizolid phosphate 2 to <6 Years; Participants will receive tedizolid phosphate once-daily single 200-mg dose (body weight ≥50 kg) or twice-daily 2-mg/kg doses (body weight 30 kg to <50 kg); or twice-daily 2.5-mg/kg doses (body weight 3.2 kg to <30 kg), by IV and/or oral suspension for 6 to 10 days.	Drug: Tedizolid phosphate; Tedizolid phosphate IV solution or oral suspension; Other Names: TR-701 FA; MK-1986
Active Comparator: Cohort 2 Comparator: 2 to <6 Years; Participants will receive comparator IV and/or oral per local standard of care for 10 to 14 days	Drug: Comparator; Vancomycin IV, linezolid IV or oral (outside European Union only), clindamycin IV or oral, flucloxacillin IV or oral, cefazolin IV, or cephalexin oral provided locally by the trial site and administered per local standard of care
Experimental: Cohort 3: Tedizolid phosphate 28 Days to <2 Years; Participants will receive tedizolid phosphate once-daily single 200-mg dose (body weight ≥50 kg) or twice-daily 2-mg/kg doses (body weight 30 kg to <50 kg); or twice-daily 2.5-mg/kg doses (body weight 3.2 kg to <30 kg), by IV and/or oral suspension for 6 to 10 days.	Drug: Tedizolid phosphate; Tedizolid phosphate IV solution or oral suspension; Other Names: TR-701 FA; MK-1986
Active Comparator: Cohort 3: Comparator: 28 Days to <2 Years; Participants will receive comparator IV and/or oral per local standard of care for 10 to 14 days	Drug: Comparator; Vancomycin IV, linezolid IV or oral (outside European Union only), clindamycin IV or oral, flucloxacillin IV or oral, cefazolin IV, or cephalexin oral provided locally by the trial site and administered per local standard of care
Experimental: Cohort 4: Tedizolid phosphate Birth to <28 Days Neonates; Participants will receive tedizolid phosphate ≤200 mg daily dose, IV and/or oral suspension for 6 to 10 days. Exact mg/kg dose is to be determined based on results of another study covering the age range.	Drug: Tedizolid phosphate; Tedizolid phosphate IV solution or oral suspension; Other Names: TR-701 FA; MK-1986
Active Comparator: Comparator: Birth to <28 Days (Term and preterm neonates); Participants will receive comparator IV and/or oral per local standard of care for 10 to14 days	Drug: Comparator; Vancomycin IV, linezolid IV or oral (outside European Union only), clindamycin IV or oral, flucloxacillin IV or oral, cefazolin IV, or cephalexin oral provided locally by the trial site and administered per local standard of care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants with ≥1 adverse events (AEs)	An AE is any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. The percentage of participants with one or more AEs will be reported.	Up to Day 35
Percentage of participants discontinuing from study therapy due to AEs	An AE is any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The percentage of participants discontinued from the study due to an AE will be reported.	Up to Day 35
Percentage of participants with hematopoietic cytopenias	A standardized MedDRA query for hematopoietic cytopenia will be conducted. The percentage of participants with a hematopoietic cytopenia will be reported.	Up to Day 35

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants with clinical success	The investigator's assessment of clinical response will be conducted at the Test of Cure (TOC) visit, approximately 25 days after the first infusion. Clinical success is defined as 1) resolution or near-resolution of most signs and symptoms, 2) absence or near-resolution of signs of infection, and 3) no new signs, symptoms, or complications attributable to the infections (no further antibiotic therapy required for the primary lesion). The percentage of participants with clinical success will be reported.	Day 25

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2019
• Primary Completion (Actual): July 6, 2023
• Study Completion (Actual): July 6, 2023

Study Registration Dates

• First Submitted: June 1, 2017
• First Submitted That Met QC Criteria: June 1, 2017
• First Posted (Actual): June 5, 2017

Study Record Updates

• Last Update Posted (Actual): July 17, 2023
• Last Update Submitted That Met QC Criteria: July 13, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Disease Attributes; Bacterial Infections; Bacterial Infections and Mycoses; Skin Diseases, Infectious; Infections; Communicable Diseases; Skin Diseases, Bacterial; Anti-Infective Agents; Anti-Bacterial Agents; Tedizolid; Tedizolid phosphate
• Other Study ID Numbers: 1986-018; MK-1986-018 (Other Identifier: Merck Protocol Number); 2016-003884-20 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No