A Global Study to find out the Effects of a Test Vaccine on prevention of harmful diseases caused by E.Coli spreading outside of the gut in Adults who are 60 Years And Older with a History of Urinary Tract Infection in the Past 2 Years.
Scientific Title of Study
Randomized, Double-blind, Placebo-controlled, Multicenter Phase 3 Study to Assess the Efficacy, Safety And Immunogenicity of Vaccination With ExPEC9V in the Prevention of Invasive Extraintestinal Pathogenic Escherichia Coli Disease in Adults Aged 60 Years And Older With a History of Urinary Tract Infection in the Past 2 Years
Trial Acronym
Embrace
Secondary IDs if Any
Secondary ID
Identifier
2020-005273-27
EudraCT
NCT04899336
ClinicalTrials.gov
VAC52416BAC3001 Amendment 5, dated 02 December 2022
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Designation
Affiliation
Address
Phone
Fax
Email
Details of Contact Person Scientific Query
Name
Dr Sanish Davis
Designation
R and D Director GCO India
Affiliation
Johnson and Johnson Private Limited
Address
Arena Space Behind Majas Depot Off J V Link Road Jogeshwari East,
Mumbai (Suburban) MAHARASHTRA 400060 India
Phone
9820958943
Fax
Email
SDavis20@ITS.JNJ.com
Details of Contact Person Public Query
Name
Dr Sanish Davis
Designation
R and D Director GCO India
Affiliation
Johnson and Johnson Private Limited
Address
Arena Space Behind Majas Depot Off J V Link Road Jogeshwari East,
Regus Kaledonia, Unit No 1B, Office No. 538, 5th Floor, Sahar Road, Off Western Express Highway, Andheri East, Mumbai- 400069
Countries of Recruitment
Australia Canada China Colombia Czech Republic Denmark France Germany India Israel Italy Japan Republic of Korea Netherlands New Zealand Spain Sweden Taiwan Thailand United Kingdom United States of America
Sites of Study
No of Sites = 13
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Deepak Varade
Asian Institute of Medical Science
Department of Medicine, P/72,
Milap Nagar, MIDC,
Dombivli (E)-421203
Mumbai MAHARASHTRA
9870409142
deepak.varade@gmail.com
Dr Rohidas Tanku Borse
B.J. Government Medical College & Sassoon General Hospitals
Head of medicine department,3rd floor, Sasson Main Building, B.J. Government Medical College & Sassoon
General Hospitals, Sassoon Road, Somwar Peth, Pune-411001. Pune MAHARASHTRA
8793226922
drborser@gmail.com
Dr Parshottam Koradia
BAPS Pramukh Swami Hospital
Clinical Research Department, Ground Floor, Shri Pramukh
Swami Maharaj Marg,
Adajan Char Rasta,
Adajan, Surat-395009,
Gujarat Surat GUJARAT
0261-2557577
ceobapshospital@gmail.com
Dr Viny Kantroo
Indraprastha Apollo Hospitals
Department of Critical Care and Sleep Medicine, Sarita Vihar
Mathura Road New Delhi
110076. South DELHI
01171791091
vinykantroo@gmail.com
Dr Tejeswini CJ
JSS Hospital
Department of Geriatric,1st floor, Mahatma
Gandhi road,
Ramachandra agrahara,
Mysore-570004,
Karnataka Mysore KARNATAKA
9980048080
tejaswinicj@jssuni.edu.in
Dr Madhav Prabhu
KLES Dr Prabhakar Kore Hospital & Medical Research Centre
OPD No 11, Ground floor, KLES Dr Prabhakar Kore
Hospital & Medical, Research Centre, Nehru Nagar, Belagavi-590010
Karnataka
Belgaum KARNATAKA
9341101268
Maddy2380@gmail.com
Dr Kapil Thakkar
Nirmal Hospital Pvt. Ltd,
Clinical Research Department, 5th floor, Ring Road, Surat-395002 Surat GUJARAT
02612236036
kapilthakkar@gmail.com
Dr Badal Kumar Sahu
NRS Medical College & Hospital,
Department of General Medicine,1st floor, Room No 8, OPD Building, NRS Medical College & Hospital, 138 A.J.C Bose
Road, Kolkata-700020,
West Bengal
Kolkata WEST BENGAL
9414459790
badalksahu@gmail.com
Dr Deepak Dewan
Regency Health SuperSpeciality Hospital,
Room No 11, Basement, Regency Health Super Specialty Hospital, Tedhi Pulia, Ring Road,
Khurram Nagar,
Lucknow-226022. Lucknow UTTAR PRADESH
Shree Giriraj Multispecialty Hospital, A Unit of Shree Giriraj Lifecare Private Limited,
CRC department ,1st floor, Shree Giriraj
Multi-specialty Hospital, A Unit of Shree Giriraj
Lifecare Private, Limited, 27- Navjyot Park
Corner, 150 feet Ring
Road, Rajkot 360005. Ahmadabad GUJARAT
9909971118
drmayankthakker@gmail.com
Dr GirishB
Shri Atal Bihari Vajpayee Medical College and research Institute, Bowring and Lady Curzon Hospital
Room 01, 1st Floor,
Admin Block annex, Shri Atal Bihari Vajpayee Medical College and research Institute, Bowring and Lady Curzon Hospital, Bangalore
560001 Bangalore KARNATAKA
9113030135
drgirishsabvmcri@gmail.com
Dr Dhananjai agrawal
SMS Superspeciality Hospital, Attached to SMS Medical College
Room No: 507, 5th Floor, Department of nephrology, SMS Superspecialty Hospital, Attached to SMS Medical College, Vivekanand Marg, C-Scheme,
Jaipur-302001 Jaipur RAJASTHAN
Institutional Ethics Committee SMS Medical College & Attached Hospital, Office of Ethics Committee, Second Floor, New Academic Block, SMS Medical college, jaipur-302004, Rajasthan
Submittted/Under Review
Institutional Ethics committee, JSS Medical college & Hospital, 3rd floor, JSS Medical College, Mysore-570015, Karnataka
Approved
Institutional Ethics Committee, B.J.G.M.C. & Sassoon General Hospitals, Sassoon Road, Station Road, Pune-411001
S.R. Kalla Memorial Ethical Committee for Human Research, S.R. Kalla Memorial Gastro & General Hospital, 78-79 Dhuleshwar Garden, Behind HSBC Bank, Sardar Patel Marg C-Scheme, Jaipur-302001, Rajasthan.
Approved
Shree Giriraj Hospital Research Ethics Committee,Shree Giriraj Multispeciality Hospital, 27- Navjyot Park Corner| 150 feet Ring Road, Rajkot 360005.
Approved
Suraksha Ethics Committee, Asian Institute of Medical Science, P/72, Milap Nagar, MIDC, Dombivli (E)421203
Participants will receive a single intramuscular (IM) injection of 9-valent extraintestinal pathogenic Escherichia coli vaccine (ExPEC9V) on Day 1. There will be a total 7 follow ups/visits post vaccination over the period of 3 years.
Comparator Agent
Placebo
Participants will receive a single IM injection of matching placebo on Day 1.There will be a total 7 follow ups/visits post vaccination over the period of 3 years.
Inclusion Criteria
Age From
60.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
1- Participant must be willing to share relevant medical information pertaining to medical history and to share medical records relevant to the medical events identified as suspected cases of invasive extraintestinal pathogenic Escherichia coli disease (IED), urinary tract infections (UTI), or acute bacterial prostatitis (ABP) occurring during the study observation period.
2- Participant must have a history of UTI in the past 2 years for which evidence of diagnosis was verified by the investigator. In case of a recent history of UTI, the condition must have resolved greater than (>)14 days prior to randomization.
3- Before randomization, participants who were born female must be either postmenopausal or permanently sterile, and not intending to conceive by any methods.
4- Participant must be willing to provide verifiable identification, has means to be contacted and to contact the investigator during the study.
ExclusionCriteria
Details
1- Participant has end stage renal disease for which dialysis is required.
2- Participant has a contraindication to intramuscular (IM) injections and blood draws example, due to bleeding disorders or a history of difficult blood draws.
3- Chronic systemic prophylactic use of antibacterials (including antibiotics and urinary tract antiseptics). Repeated courses administered for recurrent UTIs preceding randomization will not be referred to as chronic. In case of chronic prophylactic use of antibacterials, the last dose must have been administered > 60 days prior to randomization.
4- Participant has a history of acute polyneuropathy (for example, Guillain barre syndrome) or chronic inflammatory demyelinating polyneuropathy.
5- Participant has received any Escherichia coli (E. coli) or extraintestinal pathogenic Escherichia coli (ExPEC) vaccine
Method of Generating Random Sequence
Stratified randomization
Method of Concealment
Centralized
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
1-Number of Participants with First Invasive Extraintestinal Pathogenic E. coli Disease(IED) Event with Microbiological Confirmation in Blood, Other Sterile Sites, or Urine, Caused by 9 valent Extraintestinal Pathogenic E. coli Vaccine(ExPEC9V) O serotypes
2-Number of Participants with First IED Event with Microbiological Confirmation in Blood or Other Sterile Sites Caused by ExPEC9V O serotypes
Up to 3 years
Secondary Outcome
Outcome
TimePoints
Number of Participants with All IEDs (Including Multiple IEDs per Participant) Caused by ExPEC9V O-serotypes
Up to 3 years
Number of Participants with First Hospitalized IED Event Caused by ExPEC9V O-serotypes
Up to 3 years
Number of Participants with First IED Event Meeting Criteria for Sepsis Caused by ExPEC9V O-serotypes
Up to 3 years
Number of Participants with First Bacteremic IED Event Caused by ExPEC9V O-serotypes
Up to 3 years
Number of Participants with First Pyelonephritis Event Caused by ExPEC9V O-serotypes
Up to 3 years
Number of Participants with First Urinary Tract Infection (UTI) Event Caused by ExPEC9V O-serotypes
Up to 3 years
Number of Participants with All UTIs (Including Multiple UTIs per Participant) Caused by ExPEC9V O-serotypes
Up to 3 years
Number of Participants with First IED Event Caused by Any ExPEC O-serotype
Up to 3 years
Number of Participants with First Pyelonephritis Event caused By Any ExPEC O-serotype
Up to 3 years
Number of Participants with First UTI Event caused by Any ExPEC O-Serotype
Up to 3 years
Antibody Titers to Vaccine O-serotype Antigens as Determined by Multiplex Electrochemiluminescent (ECL)-based Immunoassay
Up to 3 years
Antibody Titers to Genetically Detoxified Form of Exotoxin A Derived from Pseudomonas Aeruginosa (EPA) as Determined by Multiplex ECL-based Immunoassay
Up to 3 years
Antibody Titers to Vaccine O-serotype Antigens as Determined by Multiplex Opsonophagocytic Assay (MOPA)
Up to 3 years
Number of Participants with Solicited Local Adverse Events (AEs)
Up to Day 15 (until 14 days post-vaccination)
Number of Participants with Solicited Systemic AEs
Up to Day 15 (until 14 days post-vaccination)
Number of Participants with Unsolicited AEs
Up to Day 30 (until 29 days post-vaccination)
Number of Participants with Serious Adverse Events (SAEs)
Up to 3 years
Short Form-36 (SF-36) Total Scores
Up to 3 years
European Quality of Life (EuroQol) 5-Dimension 5-Level Questionnaire (EQ-5D-5L) Scores
Up to 3 years
Change from Baseline in Frailty Index
Baseline to 3 years
Medical Resource Utilization (MRU) for IED Events
Up to Day 366 Post-IED
MRU for UTI Events
Up to Day 29 Post-UTI
MRU for Acute Bacterial Prostatitis (ABP)
Up to Day 29 Post-ABP
Number of Participants with Hospitalization for IED or, UTI, or ABP Events
Up to 3 years
Length of Stay in Hospital for IED, UTI, or ABP Events
Up to 3 years
Number of Participants with IED-related & All-cause Mortality
Up to 3 years
Target Sample Size
Total Sample Size="18556" Sample Size from India="450" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Invasive extraintestinal pathogenic Escherichia coli (ExPEC) disease is defined as an acute illness consistent with systemic bacterial infection, which is microbiologically confirmed either by the isolation and identification of Escherichia coli (E. coli) from blood or any other sterile body sites, or by the isolation and identification of E. coli from urine in a participant with urosepsis and no other identifiable source of infection. ExPEC9V (JNJ-78901563, primary compound number: VAC52416) is a 9-valent vaccine candidate in development for active immunization for the prevention of IED in adults 60 years of age and older. Although IED affects all ages, adults aged greater than or equal to (>=) 60 years have an increased risk of developing IED, including bacteremia and sepsis, which can be community-acquired, hospital-acquired or healthcare associated. As the mechanism of action of conjugate vaccines in the prevention of invasive disease is not expected to be affected by antibiotic resistance mechanisms, that is, resistance mechanisms are not linked to O-polysaccharide structures, the sponsor has no reason to expect a difference in outcome of efficacy between antimicrobial-resistant and susceptible O-serotypes. This study incorporates an inferentially seamless group-sequential design. This study consists of a Screening Phase (selected screening procedures may be performed up to 8 days prior to vaccination on Day 1), Vaccination Phase (Day 1) and Follow-up Phase (up to 3 years post-vaccination). The total study duration is up to 4 years and 2 months. Key safety assessments include serious adverse events (SAEs), solicited and unsolicited adverse events (AEs), physical examination, and vital signs