| CTRI Number |
CTRI/2023/06/053835 [Registered on: 13/06/2023] Trial Registered Prospectively |
| Last Modified On: |
11/06/2025 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
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Type of Study
|
Drug
Other (Specify) [Treatment] |
| Study Design |
Randomized, Parallel Group, Multiple Arm Trial |
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Public Title of Study
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Study to evaluate the effect of Aztreonam (ATM) and Avibactam (AVI) in pediatric participants in serious bacterial infections |
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Scientific Title of Study
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A phase 2A multicenter, observer-blinded, randomized 2 arm Study to investigate pharmacokinetics, safety, tolerability and efficacy of intravenous Aztreonam-Avibactam ± Metronidazole compared to Best Available Therapy (BAT) in pediatric participants 9 months to less than 18 years of age with serious gram-negative bacterial Infections including complicated intra-abdominal Infection |
| Trial Acronym |
|
Secondary IDs if Any
Modification(s)
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| Secondary ID |
Identifier |
| C3601008 Final Protocol dated 18 Apr 2022 |
Protocol Number |
| C3601008 Protocol Amendment 1 dated 08 Feb 2023 |
Protocol Number |
| C3601008 Protocol Amendment 2 dated 16 Jun 2023 |
Protocol Number |
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Details of Principal Investigator or overall Trial Coordinator (multi-center study)
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| Name |
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| Designation |
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| Affiliation |
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| Address |
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| Phone |
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| Fax |
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| Email |
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Details of Contact Person
Scientific Query
|
| Name |
Dr Seema Pai |
| Designation |
Director Clinical Site Operations – India Cluster |
| Affiliation |
Pfizer Limited |
| Address |
Global Site and Study Operations, Clinical Development and Operations, Global Product Development, Pfizer Products India Private Limited, The Capital, 1802/1901, Plot No. C 70, G Block, BKC, Bandra(E)
Mumbai
MAHARASHTRA
400051
India |
| Phone |
91-8826422322 |
| Fax |
|
| Email |
seema.pai@pfizer.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Seema Pai |
| Designation |
Director Clinical Site Operations – India Cluster |
| Affiliation |
Pfizer Limited |
| Address |
Global Site and Study Operations, Clinical Development and Operations, Global Product Development, Pfizer Products India Private Limited, The Capital, 1802/1901, Plot No. C 70, G Block, BKC, Bandra(E)
Mumbai
MAHARASHTRA
400051
India |
| Phone |
91-8826422322 |
| Fax |
|
| Email |
seema.pai@pfizer.com |
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Source of Monetary or Material Support
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| Pfizer Inc. 235 East 42nd Street, New York, NY 10017 |
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Primary Sponsor
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| Name |
Pfizer Inc |
| Address |
235 East 42nd Street, New York, NY 10017, USA |
| Type of Sponsor |
Pharmaceutical industry-Global |
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Details of Secondary Sponsor
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| Name |
Address |
| Pfizer Limited |
The Capital, 1802/1901, Plot No. C-70, G Block,
Bandra Kurla Complex, Bandra (E), Mumbai City - 400051, India |
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Countries of Recruitment
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China
Czech Republic
Greece
Hungary
India
Spain
Taiwan
Turkey
United States of America |
Sites of Study
Modification(s)
|
| No of Sites = 5 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Monjori Mitra |
Institute of Child Health |
11 Dr Biresh Guha Street, Kolkata, West Bengal,700017, India
Kolkata
WEST BENGAL |
91-9831075734
monjorimr@gmail.com |
| Dr Aakash Pandita |
Medanta Hospital |
Sector A, Pocket 1 Sushant Golf city, Shaheed Path, Lucknow, Uttar Pradesh, 226030, India
Lucknow
UTTAR PRADESH |
7800228811
aakash.pandita@gmail.com |
| Dr Nirmalkumar Ganeshmal Choraria |
Nirmal Hospital Pvt. Ltd |
Ring road, Surat 395002, Gujarat, India
Surat
GUJARAT |
91-9825142549
drnirmalchoraria@gmail.com |
| Dr R Prema |
RajaRajeshwari Medical College and Hospital |
No 202, Mysore Rd, Kengeri Satellite Town, No.202,Mysore Rd, Bengaluru Karnataka-560074
Bangalore
KARNATAKA |
91-9845541158
drpremar.research@gmail.com |
| Dr Pradeep Suryawanshi |
Sahyadri Super Speciality Hospital |
Survey No. 185A, Shastri Nagar, Near-MSEB Office
Yerwada, Nagar Road, Pune-411006, Maharashtra, India
Pune
MAHARASHTRA |
9923540500
drpradeepsuryawanshi@gmail.com |
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Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 5 |
| Name of Committee |
Approval Status |
| Institutional Ethics Committee Medanta Lucknow |
Submittted/Under Review |
| Institutional Ethics committee, Institute of Child Health |
Approved |
| Institutional Ethics committee, Rajarajeswari Medical College and Hospital |
Approved |
| NIRMAL HOSPITAL ETHICS COMMITTEE |
Approved |
| Sahyadri Hospitals PVT Ltd. Ethics Committee |
Approved |
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Regulatory Clearance Status from DCGI
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Health Condition / Problems Studied
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| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: K319||Disease of stomach and duodenum, unspecified, |
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Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Aztreonam-Avibactam |
Participants in the ATM-AVI group will receive multiple-dose IV infusions of a weight based fixed dose combination (3:1 ratio) of ATM-AVI. The study intervention will be
administered as an initial 3-hour IV loading dose infusion followed by 3-hour maintenance dose infusions beginning 6-8hr after the start of the loading dose and continuing q6-8hr for up to 14 days. The frequency of ATM-AVI dosing and the dose of ATM-AVI depends on renal function determined from the estimated CrCL |
| Comparator Agent |
Best Available Therapy |
BAT dose as specified in local package
insert and SoC including other medications as appropriate for anaerobic coverage |
|
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Inclusion Criteria
|
| Age From |
9.00 Month(s) |
| Age To |
18.00 Year(s) |
| Gender |
Both |
| Details |
Participants are eligible to be included in the study only if all of the following criteria apply:
Age and Sex:
1. Participants ≥9 months to <18 years of age at Screening
a) Refer below for reproductive criteria for male (Section 10.4.1) and female (Section 10.4.2) participants. Female (post-pubertal) participants must have a negative serum/urine pregnancy test (β-hCG sensitivity ≥25 mIU/mL),
Disease Characteristics:
2. Suspected/confirmed cIAI, cUTI, HAP/VAP, or BSI with gram-negative
pathogens,
3. Require hospitalization and IV antibiotic treatment.
Male Participant Reproductive Inclusion Criteria:
Male participants are eligible to participate if they agree to the following requirements
during the intervention period and for at least 7 days after the last dose of study intervention, which corresponds to the time needed to eliminate reproductive safety risk of the study intervention(s):
1. Refrain from donating sperm.
PLUS either:
2. Be abstinent from heterosexual intercourse with a female of childbearing potential as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent.
OR
3) Must agree to use a male condom when engaging in any activity that allows for passage of ejaculate to another person.
Female Participant Reproductive Inclusion Criteria:
A female participant is eligible to participate if she is not pregnant or breastfeeding, and
at least 1 of the following conditions applies:
1) Is not a WOCBP (Woman of Childbearing Potential)
OR
2) Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), as described below, during the intervention period and for at least 28 days after the last dose of study intervention, which
corresponds to the time needed to eliminate any reproductive safety risk of the study intervention(s). If a highly effective method that is user dependent is chosen, a second effective method of contraception, as described below, must
also be used. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention.
The investigator is responsible for review of medical history, menstrual history, and
recent sexual activity to decrease the risk for inclusion of a woman with an early
undetected pregnancy. |
|
| ExclusionCriteria |
| Details |
Participants are excluded from the study if any of the following criteria apply:
1. Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior 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. Gram-negative species not expected to respond to ATM-AVI ≤14 days
3. Pregnant or breastfeeding; fertile male/female unwilling/unable to use effective contraception for at ≥7 days (males) or ≥28 days (females) after last ATM-AVI infusion.
HAP/VAP only
4. Microbiologically known or high likelihood of monomicrobial infection with a gram-positive organism, lung abscess, pleural empyema, or post-obstructive pneumonia, lung or heart transplant.
5. Current use of any prohibited concomitant medication(s) or participants unwilling/unable to use a permitted concomitant medication(s).
Prior and Concomitant Therapy.
6. Received >24 hours of systemic antibiotics (abx) for ≤48hr before randomization,
except if;
a. Failed systemic abx for >48hr.
b. Not taking protocol prohibited medications,
Prior/Concurrent Clinical Study Experience:
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).Diagnostic Assessments:
7. CrCL ≤15 mL/min/1.73 m2 (eGFR calculation based on age).
8. Non-infectious related screening ALT or AST >3 x ULN, ALP >3 x ULN and/orTBili >2 x ULN (> 3 x ULN for Gilbert’s syndrome),
Other Exclusions:
9. 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. |
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Method of Generating Random Sequence
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Method of Concealment
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Blinding/Masking
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Primary Outcome
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| Outcome |
TimePoints |
(1)Maximum Predicted Plasma Concentration (Cmax) of ATM & AVI
(2)Minimum Predicted Trough Plasma Concentration (Cmin) of ATM & AVI
(3)Area under the Concentration-Time Curve (AUC) of ATM-AVI
(4)Plasma Decay Half-Life (t1/2)
(5)Apparent Clearance (CL)
(6)Proportion of Participants reporting AE
(7)Proportion of Participants reporting SAE
(8)Proportion of Participants reporting AEs leading to discontinuation
(9)Proportion of Participants reporting AEs resulting in death |
(1) Time Frame: Up to 15 Days
(2) Time Frame: Up to 15 Days
(3) Time Frame: Up to 15 Days
(4) Time Frame: Up to 15 Days
(5) Time Frame: Up to 15 Days
(6) Time Frame: Baseline up to Day 50
(7) Time Frame: Baseline up to Day 50
(8) Time Frame: Baseline up to Day 50
(9) Time Frame: Baseline up to Day 50
treatment of serious gram-negative bacterial infections in participants of 9 months to 18 years of age. |
|
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Secondary Outcome
|
| Outcome |
TimePoints |
1) Describe the efficacy of ATM-AVI and BAT
for the treatment of serious gram-negative
bacterial infections in participants of 9
months to 18 years of age. |
1) Clinical outcomes at EOIV,
EOT, and TOC.
2) Microbiological response at
EOIV, EOT, and TOC. |
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Target Sample Size
Modification(s)
|
Total Sample Size="48"
Sample Size from India="15"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
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Phase of Trial
|
Phase 2 |
|
Date of First Enrollment (India)
|
30/06/2023 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
30/01/2023 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
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Estimated Duration of Trial
|
Years="2"
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Open to Recruitment |
| Recruitment Status of Trial (India) |
Open to Recruitment |
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Publication Details
|
NIL |
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Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
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Brief Summary
|
The purpose of this study is to evaluate the PK, safety, tolerability and efficacy of intravenous ATM-AVI in participants 9 months to less than 18 years of age for the indications in which ATM-AVI is being studied in adults: cIAI, cUTI, HAP/VAP, and BSI. This study is being conducted in fulfillment of requirements in the ATM-AVI PIP1 submitted to the EMA and the ATM-AVI PSP2 submitted to the FDA.
The study is open-label with a blinded observer due to the complicated dosing regimens of the investigational product and the serious nature of the infections. Single blind study observer is a well-accepted study design in a pediatric population. Children are a vulnerable population and need close clinical monitoring by unblinded observers to interject when needed whilst the blinded observer will assess the safety and the clinical cure without bias. Given the risk to participants and severity of disease, a placebo controlled study would not be ethically appropriate. The rationale for the study design is that it provides comparative data in an open setting. |