CTRI/2024/11/077239 [Registered on: 22/11/2024] Trial Registered Prospectively
Last Modified On:
21/11/2024
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Other
Public Title of Study
A Study to Learn About the Study Medicine Aztreonam-Avibactam (ATM-AVI) in Infants and Newborns Admitted in Hospitals With Bacterial Infection
Scientific Title of Study
A phase 2a, 2-part, open-label, non-randomized, multicenter, single and multiple dose trial to evaluate Pharmacokinetics, Safety and Tolerability of Aztreonam and Avibactam plus or minus Metronidazole in neonates and infants from birth to less than 9 months of age with suspected or confirmed infections due to Gram-Negative pathogens requiring intravenous antibiotic treatment.
Trial Acronym
NIL
Secondary IDs if Any
Secondary ID
Identifier
2023-507757-15-00
EudraCT
Protocol C3601010 Protocol version 1, 27 Sep 2023
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Seema Pai
Designation
Director Clinical Site Operations
Affiliation
Pfizer Limited
Address
Pfizer Limited
The Capital, 1802/1901,
Plot No. C - 70, G Block, Bandra Kurla Complex,
Bandra (East), Mumbai
Mumbai MAHARASHTRA 400051 India
Phone
Fax
Email
seema.pai@pfizer.com
Details of Contact Person Scientific Query
Name
Dr Seema Pai
Designation
Director Clinical Site Operations
Affiliation
Pfizer Limited
Address
Pfizer Limited
The Capital, 1802/1901,
Plot No. C - 70, G Block, Bandra Kurla Complex,
Bandra (East), Mumbai
Mumbai MAHARASHTRA 400051 India
Phone
8826422322
Fax
Email
seema.pai@pfizer.com
Details of Contact Person Public Query
Name
Dr Seema Pai
Designation
Director Clinical Site Operations
Affiliation
Pfizer Limited
Address
Pfizer Limited
The Capital, 1802/1901,
Plot No. C - 70, G Block, Bandra Kurla Complex,
Bandra (East), Mumbai
MAHARASHTRA 400051 India
Phone
8826422322
Fax
Email
seema.pai@pfizer.com
Source of Monetary or Material Support
Pfizer Limited
The Capital, 1802/1901,
Plot No. C - 70, G Block, Bandra Kurla Complex,
Bandra (East), Mumbai 400 051.
Primary Sponsor
Name
Pfizer Limited
Address
The Capital, 1802/1901, Plot No. C - 70, G Block, Bandra Kurla Complex, Bandra (East), Mumbai 400 051
Type of Sponsor
Pharmaceutical industry-Indian
Details of Secondary Sponsor
Name
Address
NIL
NIL
Countries of Recruitment
United States of America Bulgaria Czech Republic Greece Hungary India Israel Italy Slovakia Spain Taiwan
Sites of Study
No of Sites = 5
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Monjori Mitra
Institute of Child health
Department: Dept of Pediatrics, Division: Project room
Room number: 113, Ground floor11 Dr Biresh Guha Street,700017 Kolkata WEST BENGAL
9831075734
monjorimr@gmail.com
Dr Akash Pandita
Medanta Lucknow Hospital
Department of Pediatrics,
Room number: OPD, B wing, Amar Shaheed Path, 226030 Lucknow UTTAR PRADESH
7800228811
aakash.pandita@gmail.com
Dr Nirmalkumar Ganeshmal Choraria
Nirmal Hospital Pvt. Ltd.
Basement- Clinical research, Ring road, Surat 395002, Gujarat, India Surat GUJARAT
Department: Dept of Pneumatology and Pediatrics
Room number: OPD Ground floor
30C, Erandwane, Karve road, 411004 Pune MAHARASHTRA
9923540500
drpradeepsuryawanshi@gmail.com
Details of Ethics Committee
No of Ethics Committees= 5
Name of Committee
Approval Status
Institutional Ethics committee ICH, Institute of Child health, 11 Dr Biresh Guha Street, Kolkata, West Bengal,700017, India.
Submittted/Under Review
Institutional Ethics committee Medanta Lucknow, Medanta Hospital Lucknow, Sector A, Pocket 1 Sushant Golf city, Shaheed Path Lucknow, Lucknow Uttar Pradesh, 226030, India
Submittted/Under Review
Institutional Ethics committee, Raja Rajeshwari Medical College and Hospital, No 202, Kambipura,Mysore Rd,Bangalore-560074,Karnataka, India
Approved
NIRMAL HOSPITAL ETHICS COMMITTEE NIRMAL HOSPITAL PVT. LTD. 2/1423-8-6 SAGRAMPURA RING ROAD NEAR CENTRE POINT SURAT 395002 GUJARAT SURAT Surat Gujarat - 395002 India
Approved
Sahyadri Hospitals Ltd. Ethics committee Sahyadri Clinical Research & Development Center (A Unit of Sahyadri Hospitals Ltd.), 33/34B, Makarand Bhave Path, Karve Road, Pune- 411004, Maharashtra, India
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: A498||Other bacterial infections of unspecified site,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Aztreonam-avibactam with or without Metronidazole (MTZ) (required for cIAI)
Study Intervention:
Part A: ATM-AVI Single Dose
Single intravenous infusion of aztreonam-avibactam over 3 hours
Part B: Multiple-dose ATM-AVI with or without Metronidazole (MTZ) (required for cIAI)
Multiple intravenous infusions of aztreonam-avibactam over 3 hours.
Comparator Agent
Not applicable
Not applicable
Inclusion Criteria
Age From
0.00 Day(s)
Age To
9.00 Month(s)
Gender
Both
Details
1. Neonates and infants age birth to less than 9 months at Screening, divided into 4 age cohorts:
Cohort 1: equal to or more than 3 months (13 weeks) to less than 9 months (39 weeks)
Cohort 2: equal to or more than 28 days (4 weeks) to less than 3 months (13 weeks)
Cohort 3: Full term (GA equal to or more than 37 weeks) birth to less than 28 days (4 weeks)
Cohort 4: Preterm (GA equal to or more than 26 to less than 37 weeks) birth to less than 28 days (less than 4 weeks)
Disease Characteristics:
2. Part A: Hospitalized, receiving IV antibiotics for treatment of suspected or confirmed bacterial infection, including but not limited to cIAI, cUTI, HAP/VAP, BSI, or sepsis
3. Part B: Hospitalized with suspected or confirmed gram-negative bacterial infection requiring IV antibiotics, including but not limited to cIAI, cUTI, HAP/VAP, BSI, or sepsis
ExclusionCriteria
Details
Medical Conditions:
1. Any medical or laboratory abnormality that may increase the risk of study
participation or, in the investigator’s judgment, make the participant inappropriate for the study.
2. Documented history of serious allergic reaction such as anaphylaxis, angioedema or bronchospasm to aztreonam or any β-lactam antibiotic.
3. Part B only, participant with cystic fibrosis, suspected or confirmed CNS infection
(eg, meningitis, shunt infection), or gram-negative species not expected to respond to ATM-AVI in equal to or less than 14 days.
Prior/Concomitant Therapy:
4. Treatment with aztreonam or ceftazidime-avibactam within 12 hours of ATM-AVI
administration.
5. Part B Only: Received more than 24 hours of systemic antibiotic treatment for gram-negative organisms during the 48 hours before screening unless documented treatment failure or lack of improvement in at least one objective sign or symptom of infection after equal to or less than 48 hours of antibiotic therapy.
6. Current use of any prohibited concomitant medication(s) or participants with cIAI or known anaerobic infection unwilling or unable to use MTZ.
Prior/Concurrent Clinical Study Experience:
7. Previous administration with an investigational product (drug or vaccine) within
30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer). Participation in studies of other investigational products (drug or vaccine) at any time during their
participation in this study.
8. Previous enrollment in this study.
Diagnostic Assessments:
9. Renal impairment or known significant renal disease, as evidenced by a serum
creatinine at screening above the 97.5th percentile for age, or urinary
output less than 0.5 mL/kg/h for 6 consecutive hours or requirement for dialysis.
10. Hepatic dysfunction as indicated by screening AST or ALT equal to or more than 3.0 × ULN.
Other Exclusion Criteria:
11. Participant is expected to be discharged less than 24 hours after the start of ATM-AVI infusion for Part A or less than 48 hours for Part B.
12. Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members.
Method of Generating Random Sequence
Not Applicable
Method of Concealment
Not Applicable
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
Maximum Predicted Plasma Concentration of Drug
Area under the Concentration-Time Curve of Drug
Plasma Elimination Half-Life
Apparent Clearance
Plasma concentrations of Drug by nominal sampling time
Proportion of Participants reporting Adverse Events, Serious Adverse Events, AEs leading to discontinuation of study drug, AEs resulting in death,liver injury and acute kidney injury
Baseline up to Day 50
Secondary Outcome
Outcome
TimePoints
Part B: Proportion of participants with each clinical outcome & with a favorable clinical outcome at end of IV study treatment (EOIV)
Up to 15 days after start of IV study treatment
Part B: Proportion of participants with each clinical outcome & with a favorable clinical outcome at end of treatment (EOT)
Within 48 hours after last dose of oral switch treatment
Part B: Proportion of participants with each clinical outcome & with a favorable clinical outcome at test of cure (TOC)
7-14 days after the last study treatment
Part B: Proportion of participants with a favorable microbiological response at TOC
7-14 days after the last study treatment
Part B: Counts & proportions of pathogens with each per-pathogen microbiological response at EOIV/EOT
Up to 15 days after start of IV study treatment
Part B: Counts & proportions of pathogens with each per-pathogen microbiological response at TOC
7-14 days after the last study treatment
Part B: Counts & proportions of participants with emergent infections (new infections or superinfections) during the study
Through study completion, up to Day 50
Target Sample Size
Total Sample Size="48" Sample Size from India="8" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Phase of Trial
Phase 2
Date of First Enrollment (India)
09/12/2024
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
25/09/2024
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="0" Months="1" Days="19"
Recruitment Status of Trial (Global)
Not Yet Recruiting
Recruitment Status of Trial (India)
Not Yet Recruiting
Publication Details
N/A
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is a 2-part Phase 2a, non-randomized, multicenter, open-label, single and multi-dose PK study to assess PK, safety, and tolerability of ATM-AVI in hospitalized neonates, including preterm neonates, and infants, aged birth to <9 months. Participants in Part A will be hospitalized and receiving intravenous antibiotic treatment for suspected or confirmed bacterial infections including but not limited to cIAI, cUTI, HAP/VAP, BSI, or sepsis. They will receive a single infusion of ATM-AVI to assess ATM-AVI PK, safety and tolerability, but not intended as treatment. Participants in Part B will be hospitalized with suspected or confirmed aerobic gram-negative bacterial infection requiring intravenous antibacterial therapy, including but not limited to cIAI, cUTI, HAP/VAP, BSI, or sepsis. Part B participants will receive multiple infusions of ATM-AVI in the hospital as treatment and to assess ATM-AVI PK, safety, tolerability, and efficacy. Participants with complicated intraabdominal infection (cIAI) will receive concomitant intravenous metronidazole because ATM-AVI does not treat anaerobes. The sponsor will attempt recruitment of an ethnically and racially diverse study population through selection of investigational sites. The study will use an external Data Monitoring Committee (DMC) for safety monitoring.