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)

Acute Bacterial Skin and Skin Structure Infections Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03176134
• Other study ID #: 1986-018
• Secondary ID: MK-1986-0182016-
• Status: Completed
• Phase: Phase 3
• Start date: January 20, 2019
• Est. completion date: July 6, 2023

Study information

• Verified date: July 2023
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: July 6, 2023
• Est. primary completion date: July 6, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 11 Years

Eligibility

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)

Related Conditions & MeSH terms

• Acute Bacterial Skin and Skin Structure Infections
• Communicable Diseases
• Infections
• Skin Diseases, Bacterial

Intervention

Drug:
• Tedizolid phosphate
Tedizolid phosphate IV solution or oral suspension
• 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

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Brazil,  Bulgaria,  Georgia,  Germany,  Guatemala,  Latvia,  Lithuania,  Mexico,  Poland,  Russian Federation,  South Africa,  Turkey,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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

External Links

•   Merck Clinical Trials Information