A Phase III Study to check the Safety and efficacy of the PCV 13 Vaccine in Healthy Infants in India in prevention of Pneumococcal disease caused by Streptococcus pneumonia.

Phase 3

Completed

• Conditions: Healthy PCV-naïve Indian male and female infants between 6-8 weeks

• Registration Number: CTRI/2022/11/047443
• Lead Sponsor: G C Chemie Pharmie Ltd

Brief Summary

Streptococcus pneumonia (S. pneumoniae), also known as pneumococcus, is the leading cause of Invasive Pneumococcal Disease (IPD). Of the estimated 8.8 million global annual deaths amongst children < 5 years of age in 2008, WHO estimated that 476,000 (333,000 to 529,000) were caused by pneumococcal infections.  Pneumococcus is a frequent inhabitant of upper respiratory tract, infants and young children are thought to be the main reservoir of this agent with cross sectional point prevalence range of 27%-85%. Pneumococcus spreads by respiratory droplet and causes pneumonia usually of the lobar type, otitis media, paranasal sinusitis, meningitis (usually secondary to former infections), septicaemia, in addition to IPD. Extreme age groups < 2 years and > 65 years have the highest IPD incidence. The incidence of acute otitis media (AOM) peaks at 6-12 months of age, and declines after 5 years of age. The 13-valent Pneumococcal Polysaccharide Conjugate Vaccine (PCV13-TT) manufactured by Yuxi Walvax Biotechnology Co., Ltd. is formulated by compounding the capsular polysaccharide antigen of Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F, individually conjugated to tetanus toxoid carrier protein. The investigational vaccine was approved for used in infants and children aged 6 months through 5 years (before the 6th birthday) and the Certificate of Drug Registration (Approval No. 2019S00755) was issued by the National Medical Products Administration (NMPA) in December 2019. The vaccine elicits immune responses in recipients following immunization, and is indicated for the prevention of invasive diseases caused by 13 serotypes of Streptococcus pneumoniae. The current study aims to develop a safe and effective 13-valent pneumococcal conjugate vaccine to reduce the global disease burden.

Detailed Description

Not available

Study Timeline

• Study Start: 2022-11-21
• Last Update Posted: 2023-06-10
• Study Completion: 2024-08-17

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 344

Inclusion Criteria

• Prospective subjects will only be eligible for randomization if all of the following inclusion criteria, and none of the exclusion criteria, are met at the time of screening: Inclusion Criteria for Primary Immunization Phase: 1.
• Healthy PCV-naïve subjects between 6-8 weeks of age (both inclusive) on the day of enrolment, whose parents/LARs are willing to participate and give written informed consent prior to the study entry.
• Subjects with good health as determined by: a)Medical history.
• b)Physical examination.
• c)Clinical judgment of the investigator.
• Subject’s parents/LARs must be able to comprehend and comply with study requirements and procedures, and willing to complete subject diary and to return with the subject for all scheduled follow-up visits.
• Subjects must have been born full-term, at randomization.
• Weight of the infant at enrolment visit ≥ 3.2 kg.
• Subjects with an up-to-date minimal vaccination status (includes, BCG vaccine, first dose of OPV, IPV and first dose of vaccine against Hep B, DPT and Hib that could be administered as pentavalent vaccine) at the time of enrolment as per UIP schedule (per local/regional protocols).
• Inclusion Criteria for Booster Immunization Phase: 1.
• Subjects who have completed primary immunization series of the investigational vaccine in the present study.

Exclusion Criteria

• Exclusion Criteria for the first dose: 1.
• The parents or LARs are unwilling or unable to give written informed consent to participate in the study.
• Subjects who have participated in another trial of an investigational agent within 30 days prior to enrolment.
• Planned participation in another clinical trial during the present trial period.
• Subjects whose families are planning to leave the area of the study site before the end of the study period.
• History of culture-proven invasive disease caused by S.
• pneumoniae.
• Subjects who have received any Pneumococcal vaccine prior to enrolment.
• Bleeding disorder, contraindicating IM vaccination, or receipt of anticoagulants in the 3 weeks preceding screening.
• History of infections with Human Immunodeficiency Virus (HIV), hepatitis B virus, or hepatitis C virus in the infant or mother.
• Presence of evolving or changing neurological disorder.
• Subjects with history of seizures.
• Axillary temperature ≥ 40.0°C in past 3 days.
• Any evidence of acute illness or infection requiring systemic antibiotic therapy within past 3 days.
• Planned or elective surgery during the course of the study.
• Subjects with a known or suspected impairment of the immune function, or those receiving immunosuppressive therapy, or having received immunosuppressive therapy within 1 month prior to study entry (including systemic corticosteroids) or those who have received a parenteral immunoglobulin preparation.
• Subjects who have received any blood products, cytotoxic agents or radiotherapy.
• Subjects with history of anaphylaxis, or any serious vaccine reaction,or allergy to any vaccine component.
• Subjects with any serious chronic disease or with any condition that in the opinion of the investigator might interfere with the evaluation of the study objectives or compromise the safety of the subject.
• Exclusion Criteria for the Second / Third Dose 1.
• Generalized allergic reaction in past 3 days .
• Encephalopathy.
• Inconsolable persisting crying (defined as > 3 hours in past 3 days).
• Exclusion Criteria for Booster immunization Phase: 1.
• Subjects who have participated in another trial after primary immunization.
• pneumonia after primary immunization.
• Subjects who have already received pneumococcal vaccine booster dose (other than investigational vaccine) from other resources (from different doctor/hospital).
• Bleeding disorder, contraindicating IM vaccination, or receipt of anticoagulants in the 3 weeks preceding booster dose.
• History of infections with Human Immunodeficiency Virus (HIV),hepatitis B virus, or hepatitis C virus in the infant after primary immunization.
• Presence of evolving or changing neurological disorder after primary immunization.
• Subjects with a known or suspected impairment of the immune function, or those receiving immunosuppressive therapy, or having received immunosuppressive therapy within 1 month prior to booster vaccination (including systemic corticosteroids) or those who have received a parenteral immunoglobulin preparation.
• Infant with any serious chronic disease or with any condition that in the opinion of the investigator might interfere with the evaluation of the study objectives or compromise the safety of the subject.
• Note that specific exclusion criteria (e.g., abnormal vital sign, acute illness) will be reassessed at all vaccination visits.
• Any subject who cannot be vaccinated due to an acute abnormality assessed at the 2nd or 3rd vaccination or booster vaccination visit may return once the acute issue has resolved.
• A minimum of 48 hours must have passed after a documented fever before a subject can be vaccinated.
• This safety requirement will not be deemed a protocol deviation should the visit fall outside the vaccination window; however, it will be encouraged to maintain the vaccination window whenever possible in these situations.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Immunogenicity	Immunogenicity | IgG responses 4 weeks after the 3rd dose of PCV13-TT or PREVENAR 13® | • Percentage of subjects achieving serotype-specific pneumococcal | immunoglobulin G (IgG) concentrations ≥ 0.35 μg/mL
IgG responses 4 weeks after the 3rd dose of PCV13-TT or PREVENAR 13®	Immunogenicity | IgG responses 4 weeks after the 3rd dose of PCV13-TT or PREVENAR 13® | • Percentage of subjects achieving serotype-specific pneumococcal | immunoglobulin G (IgG) concentrations ≥ 0.35 μg/mL
immunoglobulin G (IgG) concentrations ≥ 0.35 μg/mL	Immunogenicity | IgG responses 4 weeks after the 3rd dose of PCV13-TT or PREVENAR 13® | • Percentage of subjects achieving serotype-specific pneumococcal | immunoglobulin G (IgG) concentrations ≥ 0.35 μg/mL
• Percentage of subjects achieving serotype-specific pneumococcal	Immunogenicity | IgG responses 4 weeks after the 3rd dose of PCV13-TT or PREVENAR 13® | • Percentage of subjects achieving serotype-specific pneumococcal | immunoglobulin G (IgG) concentrations ≥ 0.35 μg/mL

Secondary Outcome Measures

Name	Time	Method
Immunogenicity and Immune persistence	IgG responses 4 weeks after booster dose of PCV13-TT or PREVENAR 13®

Trial Locations

Locations (6)

All India Institute of Medical Sciences; 🇮🇳 Patna, BIHAR, India

ESIC Medical College & Hospital; 🇮🇳 Faridabad, HARYANA, India

Jeevan Rekha Hospital; 🇮🇳 Belgaum, KARNATAKA, India

New Leelamani Hospital Pvt Ltd; 🇮🇳 Nagar, UTTAR PRADESH, India

Rajarshee Chhatrapati Shahu Maharaj Government Medical College and CPR Hospital; 🇮🇳 Kolhapur, MAHARASHTRA, India

Rana Hospital; 🇮🇳 Gorakhpur, UTTAR PRADESH, India

All India Institute of Medical Sciences

🇮🇳Patna, BIHAR, India

Dr Chandramani Singh

Principal investigator

9695237796

cmaiims57@gmail.com