A Study to Assess Sulbactam-durlobactam in Pediatric Patients With Acinetobacter Baumannii-calcoaceticus Complex Infection

Innoviva Specialty Therapeutics

Status and phase: Not yet enrolling; Phase 1

Conditions: Acinetobacter Baumannii-calcoaceticus Complex Infection (ABC)

Treatments: Drug: Sulbactam 20mg/kg-Durlobactam 20mg/kg (Every 8 hours); Drug: Sulbactam 20mg/kg-Durlobactam 20mg/kg (Every 12 hours); Drug: Sulbactam 25mg/kg -Durlobactam 25mg/kg (Every 6 hours); Drug: Sulbactam 25mg/kg -Durlobactam 25mg/kg (Every 8 hours)

Study type: Interventional

Funder types: Industry

Identifiers

NCT06801223

CS2514-2023-002

Details and patient eligibility

About

The goal of this clinical trial is to investigate the use of Sulbactam-Durlobactam (SUL-DUR) in pediatric patients and is being conducted to collect pharmacokinetic (PK) and safety data to enable the identification of appropriate pediatric dosing regimens for patients with Acinetobacter baumannii-calcoaceticus complex (ABC) infections

Enrollment: 48 estimated patients

Sex: All

Ages: 1 day to 18 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Patient from birth (defined as post-natal age of 7 days) to <18 years of age at the time of written informed consent (and assent, if applicable) and is hospitalized.
2. Patient and/or parent(s) or legal guardian(s) have provided the written informed consent and/or assent.
3. Patient has confirmed or suspected diagnosis of ABC infection and requires IV antibiotics for treatment.
4. Patient has expected survival of 30 days after enrollment in the study.
5. If patient is an individual of childbearing potential or reproductive potential, then the patient must remain abstinent OR must utilize one of the highly effective methods of contraception (ie, condom, combined oral contraceptive, implant, or injectable) from at least 30 days prior to screening until at least 30 days after administration of the last dose of study drug.

Exclusion criteria

1. Patient is a preterm infant, born at <28 weeks gestational age.

2. Patient has history of significant hypersensitivity or allergic reaction to any β-lactam, any contraindication to the excipients used in the formulation, or any contraindication to the use of β-lactam antibiotics. Note: For β-lactams, a history of a mild rash followed by uneventful re-exposure is not a contraindication to enrollment.

3. Patient is in refractory septic shock at the time of enrollment, defined as persistent hypotension despite adequate fluid resuscitation or vasopressive therapy.

4. Patient is pregnant, breastfeeding, or intends to become pregnant.

5. Patient is receiving peritoneal dialysis or cardiopulmonary bypass.

6. Patient has planned blood transfusion within 24 hours of study drug administration and for the duration of the trial.

7. Patient is a newborn with clinically significant anemia who, in the opinion of the investigator, will not be able to tolerate the necessary blood draws to complete the study activities.

8. Patient (or patient's mother, if the patient is being breastfed) is using or will need to use any medications known to inhibit organic anion transporter 1 (OAT1) (eg, probenecid).

9. Patient has clinically significant renal, hepatic, or hemodynamic instability.

10. For Cohorts 1 through 3 only: patient has weight outside of the 5th to 95th percentile based on age.

11. Patient has an age-appropriate estimated creatinine clearance that indicates renal impairment.

12. Patient has the following laboratory results at Screening:

    1. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3×upper limit of normal (ULN) and,
    2. Total bilirubin >2×ULN for age with conjugated/direct bilirubin >20% of the total. Note: Patients with AST or ALT up to 5×ULN are eligible if these elevations are acute and are documented as being directly related to the infectious process being treated.

13. Patient has clinically significant abnormal laboratory test results not related to the underlying infection that might expose the patient to risk by participating in the trial, confound the results of the trial, or interfere with the patient's participation for the full duration of the trial.

14. Patient (or patient's mother, if the patient is being breastfed) has participated in a clinical study involving investigational medication or an investigational device within the last 30 days or 5 half-lives, whichever is longer, prior to first dose of the study drug.

15. Patient has any condition that, in the opinion of the investigator, would compromise the safety of the patient or the quality of the data.

16. Patient is unable or unwilling, in the opinion of the investigator, to comply with the protocol.

17. Patient (or patient's mother, if the patient is being breastfed) has previously received durlobactam.

18. Patient (or patient's mother, if the patient is being breastfed) has received sulbactam and/or sulbactam-containing regimens (eg, Unasyn) within 72 hours of first dose of the study drug.

19. Patient (or patient's mother, if the patient is being breastfed) has received amphotericin B within 7 days of first dose of the study drug.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

---

48 participants in 6 patient groups

Cohort 1

Experimental group

Description:

Pediatric patients 12 years to \<18 years of age

Treatment:

Drug: Sulbactam 25mg/kg -Durlobactam 25mg/kg (Every 6 hours)

Cohort 2

Experimental group

Description:

Pediatric patients 6 years to \<12 years of age

Treatment:

Drug: Sulbactam 25mg/kg -Durlobactam 25mg/kg (Every 6 hours)

Cohort 3

Experimental group

Description:

Pediatric patients 1 year to \<6 years of age

Treatment:

Drug: Sulbactam 25mg/kg -Durlobactam 25mg/kg (Every 6 hours)

Cohort 4

Experimental group

Description:

Pediatric patients 3 months to \<1 year of age

Treatment:

Drug: Sulbactam 25mg/kg -Durlobactam 25mg/kg (Every 6 hours)

Cohort 5 Subgroup 1

Experimental group

Description:

Aged 2 months to \<3 months, term and preterm (gestational age \>28 weeks) Term infants will receive 25mg/kg SUL and 25mg/kg DUR Preterm infants will receive 20mg/kg SUL and 20mg/kg DUR

Treatment:

Drug: Sulbactam 25mg/kg -Durlobactam 25mg/kg (Every 6 hours)

Drug: Sulbactam 20mg/kg-Durlobactam 20mg/kg (Every 8 hours)

Cohort 5 Subgroup 2

Experimental group

Description:

Aged birth to \<2 months, term and preterm (gestational age \>28 weeks and post-natal age \>7 days) Term infants will receive 25mg/kg SUL and 25mg/kg DUR Preterm infants will receive 20mg/kg SUL and 20mg/kg DUR

Treatment:

Drug: Sulbactam 25mg/kg -Durlobactam 25mg/kg (Every 8 hours)

Drug: Sulbactam 20mg/kg-Durlobactam 20mg/kg (Every 12 hours)