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CTRI Number  CTRI/2016/05/006975 [Registered on: 31/05/2016] Trial Registered Prospectively
Last Modified On: 14/11/2018
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Vaccine 
Study Design  Randomized, Parallel Group, Active Controlled Trial 
Public Title of Study   Clinical Study to assess the immune response and safety of typhoid conjugate vaccine of Cadila Healthcare Limited and compare it to typhoid conjugate vaccine of Bharat Biotech International Limited in healthy human subjects 
Scientific Title of Study   A prospective, randomized, two-arm, parallel, single-blind, active-controlled, multicentre, non-inferiority clinical study to evaluate the immunogenicity and safety of Typhoid Vi Capsular Polysaccharide Tetanus Toxoid Conjugate Vaccine of M/s Cadila Healthcare Limited compared to Typhoid Vi Capsular Polysaccharide Tetanus Toxoid Conjugate Vaccine of M/s Bharat Biotech International Limited in healthy subjects 
Trial Acronym  None 
Secondary IDs if Any  
Secondary ID  Identifier 
Project No. 15-03; Version No. 01; Dated 16/01/2016  Protocol Number 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Ravindra Mittal 
Designation  Medical Advisor & Head - Regulatory Affairs 
Affiliation  Cadila Healthcare Ltd. 
Address  Cadila Healthcare Ltd., Sigma CommerZone, Near ISCON Temple & Satellite Cross Roads, Ambli-Bopal Road, Ahmedabad

Ahmadabad
GUJARAT
380015
India 
Phone  079-26868926  
Fax  079-26868910  
Email  r.mittal@zyduscadila.com  
 
Details of Contact Person
Scientific Query
 
Name  Dr Ravindra Mittal 
Designation  Medical Advisor & Head - Regulatory Affairs 
Affiliation  Cadila Healthcare Ltd. 
Address  Cadila Healthcare Ltd., Sigma CommerZone, Near ISCON Temple & Satellite Cross Roads, Ambli-Bopal Road, Ahmedabad


GUJARAT
380015
India 
Phone  079-26868926  
Fax  079-26868910  
Email  r.mittal@zyduscadila.com  
 
Details of Contact Person
Public Query
 
Name  Dr Pavankumar Daultani 
Designation  Senior Manager – New Product Development 
Affiliation  Cadila Healthcare Ltd. 
Address  Cadila Healthcare Ltd., Sigma CommerZone, Near ISCON Temple & Satellite Cross Roads, Ambli-Bopal Road, Ahmedabad

Ahmadabad
GUJARAT
380015
India 
Phone  079-26868937  
Fax  079-26868910  
Email  pavankumar.daultani@zyduscadila.com  
 
Source of Monetary or Material Support  
Cadila Healthcare Ltd., Ahmedabad 
 
Primary Sponsor  
Name  Cadila Healthcare Ltd 
Address  Cadila Healthcare Ltd., Sigma CommerZone, Near ISCON Temple & Satellite Cross Roads, Ambli-Bopal Road, Ahmedabad – 380015, Gujarat, India 
Type of Sponsor  Pharmaceutical industry-Indian 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study
Modification(s)  
No of Sites = 8  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr T Ramesh Babu  Gandhi Medical College & Hospital, Secunderabad  Study room, 1st floor, hospital main building, Department of Pediatrics, Gandhi Hospital, Musheerabad, Secunderabad - 500003
Hyderabad
ANDHRA PRADESH 
09247119597

ramesh_ped@yahoo.com 
Dr Ambrose Kumar Kandulna  GCS Medical College, Hospital & Research Centre, Ahmedabad  Room No. 13, Medicine OPD, Department of Medicine, GCS Medical College, Hospital & Research Centre, Opp. DRM Office, Near Chamunda Bridge, Naroda Road, Ahmedabad – 380025
Ahmadabad
GUJARAT 
07698059533

drambrosek@gmail.com 
Dr Uma Nayak  GMERS Medical College & General Hospital, Vadodara  Room No. 501, 5th floor, Hospital building, Department of Pediatrics, GMERS Medical College & General Hospital, Gotri, Vadodara 390021
Vadodara
GUJARAT 
09327214065

umasnayak@gmail.com 
Dr Sanjay Kumar Jangid  Hi-Tech Medical College & Hospital, Bhubaneswar  Medicine OPD, Department of Medicine, Hi-Tech Medical College & Hospital, Health Park, Pandara, Rasulgarh, Bhubaneswar-751025
Khordha
ORISSA 
09337671521

drsanjay_jangid@yahoo.co.in 
Dr Rajesh Vukkala  Indo-US Superspeciality Hospital, Hyderabad  Room No. 2, Ground Floor, Indo-US Superspeciality Hospital, Shyam Karan Road, Ameerpet, Hyderabad-500016
Hyderabad
ANDHRA PRADESH 
07702116066

vukkala@gmail.com 
Dr Ritabrata Kundu  Institute of Child Health, Kolkata  Room No. 113, Ground floor, Institute of Child Health, 11, Dr. Biresh Guha Street Kolkata – 700017, West Bengal
Kolkata
WEST BENGAL 
09831194865

rkundu22@gmail.com 
Dr Vimal Kant Goyal  Panchsheel Hospital, Delhi   Pediatric OPD, Ground floor, Panchsheel Hospital Pvt. Ltd., Opp. Gokul Puri Police Station, Yamuna Vihar, Delhi- 110053
New Delhi
DELHI 
09810106800

vkgoyal22@gmail.com 
Dr Shrikant Sharma  SMS Medical College & Hospital, Jaipur  Medicine Unit VII, 2nd floor, Hospital building, Department of Medicine, SMS Medical College & Hospital, JLN Marg, Jaipur-302004
Jaipur
RAJASTHAN 
09214403945

skant_sunita@yahoo.co.in 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 8  
Name of Committee  Approval Status 
Ethics Committee, Institute of Child Health, 11, Dr. Biresh Guha Street, Kolkata, West Bengal  Approved 
Ethics Committee, Panchsheel Hospital, Opp. Gokal Puri Police Station, Yamuna Vihar, New Delhi  Approved 
Institutional Ethics Committee (Institutional Review Board) GMERS Medical College Gotri, Gotri Road, Vadodara, Gujarat  Approved 
Institutional Ethics Committee, Gandhi Medical College & Hospital, Musheerabad, Secundrabad – 500003  Approved 
Institutional Ethics Committee, GCS Medical college, Hospital & Research Centre, Opp. DRM office, Nr. Chamunda Bridge, Naroda Road, Ahmedabad, Gujarat  Approved 
Institutional Ethics Committee, Hi-Tech Medical College & Hospital, Health Park, Pandara, Rasulgarh, Bhubaneswar, Orissa  Approved 
Institutional Ethics Committee, Indo-US Superspeciality Hospital, Shyam Karan Road, Ameerpet, Hyderabad  Approved 
The Ethics Committee, SMS Medical College & Attached Hospitals, Dhanvantri OPD Block, SMS Hospital, JLN Marg, Jaipur, Rajasthan  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied
Modification(s)  
Health Type  Condition 
Healthy Human Volunteers  Active immunization for the prevention of typhoid fever caused by Salmonella Typhi bacteria 
Patients  (1) ICD-10 Condition: Z23||Encounter for immunization,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  Typhoid Vi Capsular Polysaccharide Tetanus Toxoid Conjugate Vaccine of M/s Cadila Healthcare Limited  Subjects will receive 0.5 ml single dose of Typhoid Vi Capsular Polysaccharide Tetanus Toxoid Conjugate Vaccine administered as intramuscular injection in the deltoid muscle in the upper arm or in the anterolateral aspect of the thigh (for younger children) taking aseptic precautions on day 0. The subjects will be followed up till 42 days post-vaccination 
Comparator Agent  Typhoid Vi Capsular Polysaccharide Tetanus Toxoid Conjugate Vaccine of M/s Bharat Biotech International Limited  Subjects will receive 0.5 ml single dose of Typhoid Vi Capsular Polysaccharide Tetanus Toxoid Conjugate Vaccine administered as intramuscular injection in the deltoid muscle in the upper arm or in the anterolateral aspect of the thigh (for younger children) taking aseptic precautions on day 0. The subjects will be followed up till 42 days post-vaccination 
 
Inclusion Criteria  
Age From  6.00 Month(s)
Age To  45.00 Year(s)
Gender  Both 
Details  1. Healthy subjects of either gender between 6 months to 45 years of age
2. Informed consent from adult subjects or from subject’s legally acceptable representative for non-adult subjects. Additionally, assent from non-adult subjects of more than 7 years of age
3. Adult subject or legally acceptable representative of non-adult subject literate enough to fill the diary card 
 
ExclusionCriteria 
Details  1. History of hypersensitivity reaction to any component of the study vaccines
2. History of typhoid fever or vaccination against typhoid fever within the last three years
3. Fever of any origin or infections of more than 3 days within the past month
4. Subjects with febrile illness (temperature ≥ 37.5 C) at the time of enrollment
5. History of any vaccination within the past 7 days
6. Clinically significant systemic disorder such as cardiovascular, respiratory, neurologic, gastrointestinal, hepatic, renal, endocrine, hematological or immunological disorder
7. Subjects with confirmed or suspected immunosuppressive or immunodeficiency disorder; or subjects on any immunosuppressive or immunostimulant therapy
8. Known case of thrombocytopenia or any coagulation disorder, or subjects on anticoagulation therapy
9. Subjects administered blood, blood containing products or immunoglobulins within the last 3 months or planned administration during the study
10. Pregnant and lactating women & female subjects not using acceptable contraceptive measures (double barrier methods, oral or injectable hormonal contraceptives or surgical sterilization)
11. Participation in another clinical trial in the past 3 months
12. Subjects with history of alcohol or drug abuse in the past one year 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   An Open list of random numbers 
Blinding/Masking   Participant Blinded 
Primary Outcome  
Outcome  TimePoints 
Sero-conversion rate i.e., Proportion of subjects with ≥ 4 fold rise in anti-Vi IgG antibodies 42 days post-vaccination as compared to baseline  42 days post-vaccination 
 
Secondary Outcome  
Outcome  TimePoints 
Geometric mean titre of anti-Vi IgG antibodies at baseline and 42 days post-vaccination  42 days post-vaccination 
Sero-conversion rate in anti-Vi IgG antibodies 42 days post-vaccination as compared to baseline in both age groups  42 days post-vaccination 
Geometric mean titre of anti-Vi IgG antibodies at baseline and 42 days post-vaccination in subjects in both age groups  42 days post-vaccination 
 
Target Sample Size   Total Sample Size="238"
Sample Size from India="238" 
Final Enrollment numbers achieved (Total)= "240"
Final Enrollment numbers achieved (India)="240" 
Phase of Trial   Phase 2/ Phase 3 
Date of First Enrollment (India)
Modification(s)  
03/06/2016 
Date of Study Completion (India) 07/11/2016 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Date Missing 
Estimated Duration of Trial   Years="0"
Months="9"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  
Not Applicable 
Recruitment Status of Trial (India)  Completed 
Publication Details   NA 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Brief Summary
Modification(s)  

This is a randomized, parallel group, multicentre, non-inferiority phase II/III clinical trial to evaluate the immunogenicity and safety of Typhoid Vi capsular polysaccharide tetanus toxoid conjugate vaccine of M/s. Cadila Healthcare Ltd. (Test vaccine) as compared to Typhoid Vi capsular polysaccharide tetanus toxoid conjugate vaccine of M/s. Bharat Biotech International Ltd. (Reference vaccine) in healthy subjects of 6 months to 45 years of age. There will be two age cohorts in this study; Adult cohort & Pediatric cohort. The enrollment in this study will be sequential in nature wherein the adult subjects (18 to 45 years) will be enrolled prior to the enrollment of pediatric subjects (6 months to 17 years). A minimum of 238 subjects will be enrolled in this study and will receive either study vaccine as per the central computer generated randomization plan. Two blood samples will be collected; once pre-vaccination (on day 0) & another post-vaccination (on day 42) to determine anti-Vi IgG antibody titre through ELISA method. The primary efficacy/immunogenicity endpoint of this study is to demonstrate the non-inferiority of test vaccine to the reference vaccine for the proportion of subjects with seroconversion (≥ 4 fold rise) for anti-Vi IgG antibodies post-vaccination. In addition, geometric mean titre of anti-Vi IgG antibodies at the baseline and at the end of study will also be calculated for both the study groups. The safety of the study vaccines will be assessed by recording the adverse events occurring during the entire course of the study.

 
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