Safety, Tolerability, Efficacy and Pharmacokinetics of Imipenem/Cilastatin/Relebactam (MK-7655A) in Pediatric Participants With Gram-negative Bacterial Infection (MK-7655A-021)

NCT03969901 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: 7655A-021MK-7655A-0212019-000338-20
• Study Type: interventional
• Target: 115
• Locations: 17 countries
• Sites: 66

Brief Summary

The primary purpose of this study is to evaluate the safety and tolerability of imipenem/cilastatin/relebactam (IMI/REL) in participants from birth to less than 18 years of age with confirmed or suspected gram-negative bacterial infection. Participants are expected to require hospitalization through completion of intravenous (IV) study intervention, and have at least one of the following primary infection types: hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP); complicated intra-abdominal infection (cIAI); or complicated urinary tract infection (cUTI). Participants will be randomized in a 3:1 ratio to receive IMI/REL or active control. This study will also evaluate the efficacy of IMI/REL by assessing all-cause mortality at Day 28 post-randomization, as well as clinical and microbiological response to treatment. It will also evaluate the pharmacokinetics of IMI/REL.

Conditions

Suspected or Documented Gram-negative Bacterial Infection

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With One or More Adverse Event (AE)

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants with AEs are presented.

  Up to 28 days

• Percentage of Participants Who Discontinued Study Medication Due to an Adverse Event (AE)

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who discontinued study medication due to an AE are presented.

  Up to 14 days

Secondary Outcomes (12)

• Percentage of Participants With All-cause Mortality Through Day 28

  Up to Day 28

• Percentage of Participants With a Favorable Clinical Response at End of Therapy (EOT)

  Day 5 up to Day 14

• Percentage of Participants With a Favorable Clinical Response at Early Follow-Up (EFU)

  Day 12 up to Day 28

• Percentage of Participants With a Favorable Clinical Response at Late Follow-Up (LFU)

  Baseline and Day 19 up to Day 42

• Percentage of Participants With a Favorable Microbiological Response at End of Therapy (EOT)

  Day 5 up to Day 14

Study Arms (2)

IMI/REL

EXPERIMENTAL

Participants with cIAI or cUTI will receive imipenem/cilastatin/relebactam (IMI/REL) via IV infusion for a minimum of 5 days (with optional investigator's choice of locally sourced oral switch medication after 3 days) up to a maximum of 14 days. Participants with HABP/VABP will receive IMI/REL via IV infusion for a minimum of 7 days up to a maximum of 14 days. Participants with bacteremia or Pseudomonas aeruginosa infection will receive IMI/REL via IV infusion for 14 days. All oral switch medications will be chosen from a list of acceptable approved agents and will be administered per authorized Package Insert (PI), Summary of Product Characteristics (SPC), or international treatment guidelines.

Drug: IMI/REL; Drug: Oral Switch

Active Control

ACTIVE COMPARATOR

Participants with cIAI or cUTI will receive active control via IV infusion for a minimum of 5 days (with optional investigator's choice of locally sourced oral switch medication after 3 days) up to a maximum of 14 days. Participants with HABP/VABP will receive active control via IV infusion for a minimum of 7 days up to a maximum of 14 days. Participants with bacteremia or Pseudomonas aeruginosa infection will receive active control via IV infusion for 14 days. All active control and oral switch medications will be administered per authorized PI, SPC, or international treatment guidelines. All active control and oral switch medications will be chosen from a list of acceptable approved agents.

Drug: Active Control; Drug: Oral Switch

Interventions

IMI/REL DRUG

Age-based dosing: * 12 to \<18 years, IMI 500 and REL 250 mg, IV infusion every 6 hours * 6 to \<12 years, IMI 15 and REL 7.5 mg/kg, IV infusion every 6 hours * 2 to \<6 years, IMI 15 and REL 7.5 mg/kg, IV infusion every 6 hours * 3 months to \<2 years, IMI 15 and REL 7.5 mg/kg, IV infusion every 6 hours * Birth to \<3 months, IMI 15 and REL 7.5 mg/kg, IV infusion every 8 hours NOTE: Participants with cIAI or cUTI may be switched to oral therapy after at least 3 days of IV study intervention.

Also known as: MK-7655A

IMI/REL

Active Control DRUG

All active control medications will be chosen from a list of acceptable approved agents for each infection type (HABP or VABP, cIAI, and UTI) and will be given via IV infusion, per authorized Package Insert (PI), Summary of Product Characteristics (SPC), or international treatment guidelines. NOTE: Participants with cIAI or cUTI may be switched to oral therapy after at least 3 days of IV study intervention. All oral switch medications will be chosen from a list of acceptable approved agents.

Active Control

Oral Switch DRUG

All oral switch medications will be investigator's choice from a list of acceptable approved agents for infection types cIAI, and cUTI and will be given per authorized Package Insert (PI), Summary of Product Characteristics (SPC), or international treatment guidelines. Participants with cIAI or cUTI may be switched to oral therapy after at least 3 days of IV study intervention.

Active Control; IMI/REL

Eligibility Criteria

• Age: Up to 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Requires hospitalization and treatment with intravenous (IV) antibacterial therapy for confirmed or suspected gram-negative bacterial infection (in the absence of meningitis), and is expected to require hospitalization through completion of IV study intervention, with at least 1 of the following primary infection types: Hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP); complicated intra-abdominal infection (cIAI); or complicated urinary tract infection (cUTI).
• For Age Cohorts 4 and 5, participant is at least 37 weeks postmenstrual age at the time of signing the informed consent/assent.
• If female, must not be pregnant or breastfeeding, and at least 1 of the following conditions must apply: must not be a woman of childbearing potential (WOCBP); OR, if a WOCBP, must agree to follow contraceptive guidance during the intervention period and for at least 24 hours after the last dose of study intervention.
• Has sufficient intravascular access to receive study drug through an existing peripheral or central line.

You may not qualify if:

• Is expected to survive less than 72 hours.
• Has a concurrent infection that would interfere with evaluation of response to the study antibacterials (imipenem/cilastatin/relebactam (IMI/REL) or Active Control), including any of the following: endocarditis; osteomyelitis; meningitis; prosthetic joint infection; active pulmonary tuberculosis; disseminated fungal infection; concomitant infection at the time of randomization that requires non-study systemic antibacterial therapy in addition to IV study treatment or oral step-down therapy (medications with only gram-positive activity \[e.g., vancomycin, linezolid\] are allowed).
• Has HABP/VABP caused by an obstructive process, including lung cancer (or other malignancy metastatic to the lungs resulting in pulmonary obstruction) or other known obstruction.
• Has a cUTI, with any of the following: complete obstruction of any portion of the urinary tract (i.e., requiring a permanent indwelling urinary catheter or instrumentation); documented reflux of ileal loop urinary diversion; suspected or confirmed perinephric or intrarenal abscess; suspected or confirmed prostatitis, urethritis, or epididymitis; trauma to pelvis/urinary tract; presence of indwelling urinary catheter which cannot be removed at study entry.
• Has any of the following medical conditions at screening: history of a seizure disorder (requiring ongoing treatment with anti-convulsive therapy or prior treatment with anti-convulsive therapy within the last 3 years); cystic fibrosis; history of serious allergy, hypersensitivity (e.g., anaphylaxis), or any serious reaction to IMI, or to any carbapenem, cephalosporin, penicillin, or other β-lactam agent, or to other β-lactamase inhibitors (e.g., tazobactam, sulbactam, clavulanic acid, avibactam).
• Has a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might expose the participant to risk by participating in the study, confound study results, or interfere with the participant's participation for the full duration of the study.
• If less than 3 months of age, has received more than 72 hours of empiric antibacterial treatment for suspected meningitis prior to initiation of IV study intervention.
• For all Age Cohorts, provided all other eligibility criteria are met, the following participants may be enrolled:
• A participant failing prior antibiotic therapy for a current episode of cUTI or HABP/VABP who: Has received the prior antibacterial treatment for at least 48 hours; Has persistent clinical or radiographic findings clearly indicating ongoing infection; Fulfills other laboratory or microbiology criteria for enrollment
• A participant failing prior antibiotic therapy for a current episode of cIAI who: Has received the prior antibacterial treatment for at least 48 hours; Has persistent clinical or radiographic findings clearly indicating ongoing infection; Fulfills other laboratory or microbiology criteria for enrollment; Has planned operative intervention no more than 24 hours after first dose of study treatment; Has not received any further nonstudy antibiotics postoperatively
• If 3 months of age or older, or \<3 months of age without suspected meningitis, has received potentially therapeutic antibacterial therapy (e.g., with gram-negative activity), including bladder infusions with topical urinary antiseptics or antibacterial agents, for a duration of more than 24 hours during the 48 hours preceding the first dose of study intervention.
• Is anticipated to be treated with any of the following medications: valproic acid or divalproex sodium (or has used valproic acid or divalproex sodium in the 2 weeks prior to screening) through 24 hours after completion of the final dose of IV study intervention for participants who receive IMI/REL or carbapenem; concomitant IV, oral, or inhaled antimicrobial agents with gram-negative activity, in addition to those designated in the study intervention groups, during the course of all (IV/oral) study intervention; planned receipt of suppressive/prophylactic antibiotics with gram-negative activity after completion of study intervention.
• Is currently participating in or has participated in an interventional clinical study with an investigational compound or device within 30 days prior to screening.
• Has enrolled previously in the current study and been discontinued or has received REL for any other reason.
• Has an estimated creatinine clearance (based on the Cockcroft-Gault equation, for participants ≥12 years of age or estimated glomerular filtration rate (eGFR), based on the modified Schwartz equation, for participants \<12 years of age below that specified for the appropriate age range; or requires peritoneal dialysis, hemodialysis, or hemofiltration.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (67)

Banner University Medical Center ( Site 0356)

Tucson, Arizona, 85724, United States

Location

Miller Children's & Women's Hospital ( Site 0349)

Long Beach, California, 90806, United States

Location

Rady Children's Hospital-San Diego ( Site 0347)

San Diego, California, 92123, United States

Location

Tufts Medical Center-Floating Hospital for Children ( Site 0350)

Boston, Massachusetts, 02111, United States

Location

University of New Mexico ( Site 0358)

Albuquerque, New Mexico, 87106, United States

Location

University Hospital ( Site 0360)

San Antonio, Texas, 78229, United States

Location

Children's Hospital of Richmond at VCU ( Site 0359)

Richmond, Virginia, 23298, United States

Location

West Virginia University Ruby Memorial Hospital ( Site 0344)

Morgantown, West Virginia, 26506, United States

Location

UMHAT Deva Maria. EOOD ( Site 0165)

Burgas, 8127, Bulgaria

Location

MHAT City Clinic Sv. Georgi EOOD ( Site 0167)

Montana, 3400, Bulgaria

Location

UMHAT Dr. Georgi Stranski EAD ( Site 0174)

Pleven, 5800, Bulgaria

Location

UMHAT Kanev AD ( Site 0168)

Rousse, 7002, Bulgaria

Location

UMHAT Kanev AD ( Site 0169)

Rousse, 7002, Bulgaria

Location

MHAT Dr. Ival Seliminski ( Site 0173)

Sliven, 8800, Bulgaria

Location

Hospital Roberto del Río ( Site 0802)

Santiago, Region M. de Santiago, 8380418, Chile

Location

Fundacion Hospital San Vicente de Paul ( Site 0269)

Medellín, Antioquia, 050010, Colombia

Location

Clinica de la Costa S.A.S. ( Site 0264)

Barranquilla, Atlántico, 080020, Colombia

Location

Sociedad de Cirugía de Bogotá - Hospital de San Jose ( Site 0265)

Bogotá, Bogota D.C., 11001000, Colombia

Location

Fundacion Hospital Infantil Universitario de San Jose ( Site 0268)

Bogotá, Bogota D.C., 111211, Colombia

Location

Fundacion Valle del Lili ( Site 0266)

Cali, Valle del Cauca Department, 760032, Colombia

Location

Tallinn Children Hospital ( Site 0209)

Tallinn, Harju, 13419, Estonia

Location

Hopitaux Pediatriques CHU Lenval ( Site 0143)

Nice, Alpes-Maritimes, 06200, France

Location

Hopital Francois Mitterand ( Site 0146)

Dijon, Cote-d Or, 21000, France

Location

Hopital Jeanne de Flandre ( Site 0145)

Lille, Hauts-de-France, 59120, France

Location

University of Athens - Aghia Sophia Childrens Hospital ( Site 0243)

Athens, Attica, 115 27, Greece

Location

Pan and Aglaia Kyriakou Children s Hospital ( Site 0247)

Athens, Attica, 11527, Greece

Location

Hippokration General Hospital of Thessaloniki ( Site 0244)

Thessaloniki, 546 42, Greece

Location

Debreceni Egyetem Klinikai Kozpont ( Site 0100)

Debrecen, Hajdú-Bihar, 4032, Hungary

Location

Szabolcs-Szatmar-Bereg Megyei Kórházak és Egyetemi Otatókórház-Gyermekosztály ( Site 0105)

Nyíregyháza, Szabolcs-Szatmár-Bereg, 4400, Hungary

Location

Rambam Medical Center ( Site 0189)

Haifa, 3109601, Israel

Location

Hadassah Ein Karem Hebrew University Medical Center ( Site 0188)

Jerusalem, 9112001, Israel

Location

Schneider Children's Medical Center ( Site 0187)

Petah Tikva, 4920235, Israel

Location

Chaim Sheba Medical Center ( Site 0190)

Ramat Gan, 5262100, Israel

Location

Hospital General de Tijuana ( Site 0284)

Tijuana, Estado de Baja California, 22000, Mexico

Location

Hospital del Nino y Adolescente Morelense ( Site 0286)

Emiliano Zapata, Morelos, 62765, Mexico

Location

Centenario Hospital Miguel Hidalgo-Pediatrics Department ( Site 0290)

Aguascalientes, 20259, Mexico

Location

Instituto Nacional de Pediatria ( Site 0291)

Mexico City, 04530, Mexico

Location

Haukeland Universitetssjukehus ( Site 0500)

Bergen, Hordaland, 5009, Norway

Location

University of the Philippines-Philippine General Hospital ( Site 0318)

Manila, National Capital Region, 1000, Philippines

Location

Philippine Children s Medical Center ( Site 0317)

Quezon City, National Capital Region, 1104, Philippines

Location

Wojewodzki Szpital Zespolony im. Rydgiera ( Site 0220)

Torun, Kuyavian-Pomeranian Voivodeship, 87-100, Poland

Location

SPZOZ im. Dzieci Warszawy w Dziekanowie Lesnym ( Site 0226)

Łomianki, Masovian Voivodeship, 05-092, Poland

Location

Instytut Centrum Zdrowia Matki Polki ( Site 0223)

Lodz, Łódź Voivodeship, 93-338, Poland

Location

Pediatric Hematology Oncology and Immunology Centre n.a. D.Rogachev. ( Site 0233)

Moscow, Moscow, 117197, Russia

Location

Morozovskaya Children City Clinical Hospital ( Site 0241)

Moscow, Moscow, 119049, Russia

Location

State Budgetary Healthcare Institution of Novosibirsk Region City Childrens Clinical Emergency Hospi

Novosibirsk, Novosibirsk Oblast, 630011, Russia

Location

Children s City Clinical Hospital 5 n.a. N.F. Filatov ( Site 0235)

Saint Petersburg, Sankt-Peterburg, 192289, Russia

Location

St.Petersburg State Pediatric Medical University ( Site 0236)

Saint Petersburg, Sankt-Peterburg, 194100, Russia

Location

Children's City Clinical Hospital #1 ( Site 0237)

Saint Petersburg, Sankt-Peterburg, 198205, Russia

Location

Smolensk Regional Clinical Hospital ( Site 0231)

Smolensk, Smolensk Oblast, 214018, Russia

Location

Regional Childrens Clinical Hospital ( Site 0400)

Vologda, Vologda Oblast, 160022, Russia

Location

Empilweni Services and Research Unit ( Site 1557)

Johannesburg, Gauteng, 2001, South Africa

Location

Chris Hani Baragwanath Academic Hospital ( Site 0156)

Johannesburg, Gauteng, 2013, South Africa

Location

Molotlegi Street ( Site 0155)

Pretoria, Gauteng, 0208, South Africa

Location

Hospital Infantil Universitario Nino Jesus ( Site 0114)

Madrid, 28009, Spain

Location

Hospital Universitario La Paz ( Site 0113)

Madrid, 28046, Spain

Location

Hospital Universitario Virgen del Rocio ( Site 0115)

Seville, 41043, Spain

Location

Cukurova University Medical Faculty ( Site 0200)

Adana, 01330, Turkey (Türkiye)

Location

Ankara Universitesi Tip Fakultesi. ( Site 0202)

Ankara, 06590, Turkey (Türkiye)

Location

Eskisehir Osmangazi University Medical ( Site 0201)

Eskişehir, 26480, Turkey (Türkiye)

Location

SBU Sariyer Hamidiye Etfal Egitim ve Arastirma Hastanesi ( Site 0198)

Istanbul, 34453, Turkey (Türkiye)

Location

Ege Universitesi Tıp Fakultesi Hastanesi ( Site 0199)

Izmir, 35100, Turkey (Türkiye)

Location

SI Dnipropetrovsk Regional Children Clinical Hospital DOR ( Site 0121)

Dnipro, Dnipropetrovsk Oblast, 49100, Ukraine

Location

Communal non-commercial enterprise "Kryvorizka city clinical hospital 16" of Kryvyy Rig city council

Kryvyy Rig, Dnipropetrovsk Oblast, 50082, Ukraine

Location

Ivano-Frankivsk Regional Children Clinical Hospital ( Site 0131)

Ivano-Frankivsk, Ivano-Frankivsk Oblast, 76014, Ukraine

Location

Kharkiv City Children Hospital 16 ( Site 0130)

Kharkiv, Kharkivs’ka Oblast’, 61075, Ukraine

Location

Municipal Enterprise Children's City Clinical Hospital in Poltava City Council ( Site 0122)

Poltava, Poltava Oblast, 36004, Ukraine

Location

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@msd.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2019
• First Posted: May 31, 2019
• Study Start: October 8, 2019
• Primary Completion: May 7, 2024
• Study Completion: May 7, 2024
• Last Updated: February 5, 2026
• Results First Posted: May 13, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

FR (3); PL (3); RU (8); PH (2); CL (1); HU (2); ZA (3); BU (6); TU (5); UA (5); CO (5); ES (3); NO (1); IL (4); US (8); GR (3); ME (4)