Clinical trial NCT06413121: Clinical Study to Assess the Immunogenicity and Safety of Hexavalent Vaccine Containing Reduced Dose IPV
Official title: An Observer-blind, Randomized, Active-controlled, Multi-centric Phase III Study to Assess Immunogenicity and Safety of Hexavalent (DTwP-Hepatitis B-IPV-Hib) Vaccine Containing Reduced Dose IPV in Comparison With HEXASIIL®
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Diptheria Immunization
Tetanus Immunization
Pertussis Immunization
Hepatitis B Immunization
Haemophilus Influenzae Type B Immunization
Polio Immunization
Lead sponsor: Serum Institute of India Pvt. Ltd.
Sponsor class: INDUSTRY
First posted: 2024-05-14
Enrollment: 1557
Sex: ALL
Minimum age (years): 6
Maximum age (years): 8
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: In 2012, the World Health Assembly (WHA) endorsed the proposed Polio Endgame Strategy, which includes withdrawal of the Sabin-virus type 2 antigen-responsible for an estimated 95% of vaccine derived cases of polio by replacing the trivalent Oral Polio Vaccine (OPV) in the routine immunization schedule with a bivalent OPV that lacks the type 2 Sabin virus. Since the WHA resolution, all countries that were solely using OPV have either introduced Inactivated Polio Vaccine (IPV) into their routine immunization schedule or decided to introduce IPV but have been unable to secure supply. The global demand for IPV has therefore substantially increased in just a few years. Many initiatives are ongoing to meet the increasing demand for IPV. One potential approach is the reduction of the amount of antigen per vaccine dose. Therefore, to enhance the affordability, effectiveness and accessibility of IPV.

SIIPL has manufactured hexavalent combination vaccine containing diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type b and a reduced dose of three IPV antigens.

Based on available published data, reduction of the antigen content of each of the three poliovirus types in IPV is feasible, without substantially compromising the immunogenicity of the vaccine. Advantages of a reduction in antigen content are two-fold: increased availability of IPV and reduced cost, both of major importance for the global eradication programme.

Detailed description: This is an observer-blind, randomized, active-controlled, multi-centric study in healthy infants and toddlers to assess the immunogenicity and safety of SIIPL reduced IPV hexavalent vaccine in comparison with the licensed SIIPL HEXASIIL® vaccine.

One thousand five hundred and fifty-seven infants aged 6-8 weeks (42 to 56 days, both days inclusive) will be randomized in a 2:1 ratio (1038 infants in SIIPL reduced IPV hexavalent group and 519 in SIIPL HEXASIIL® group), to receive a 3-dose primary vaccination series followed by their booster doses, respectively. The safety and immunogenicity data collected up to 28 days following third vaccination i.e., Visit 7, shall be submitted to the regulatory authority. All subjects will be followed up further for booster dose. After Visit 7 (i.e., 28 days following completion of primary vaccination series) subjects will be followed up for safety every 3 months starting from the age of 6 months (i.e., at 6, 9, 12, 15, 18, and 21 months of age) until they receive the booster dose anytime between 12-24 months. There will be post booster follow up visit (EOS visit) 28 days after the booster immunization i.e., Visit 10 to assess the safety and post booster immunogenicity.

Eligibility criteria: Inclusion Criteria:

* Male or female infants aged 6-8 weeks at the time of first vaccination.
* Infants with good health, as determined by the medical history, physical examination and clinical judgment of the Investigator.
* Informed consent form signed by at least one parent.
* Infants born at full term pregnancy (≥ 37 weeks).
* Infants with weight-for-length z-score ≥ -2 standard deviation (SD) at the time of enrolment.
* Willingness of subjects' parent to comply with the requirements of the protocol.

Exclusion Criteria:

* History of diphtheria/ tetanus/ pertussis/ hepatitis B/ Haemophilus Influenzae type b/ poliomyelitis infection(s).
* Presence of fever ≥ 38°C/ 100.4°F.
* Acute illness of moderate to severe intensity according to the clinical judgment of the investigator .
* Receipt of antibiotics in the past 3 days
* Previous vaccination or planned receipt of any vaccine against diphtheria, tetanus, pertussis, hepatitis B (except birth dose), poliomyelitis (except OPV birth dose) or Haemophilus Influenzae type b infection apart from trial vaccines during the study period.
* Administration of any vaccine (except OPV during government immunization campaign) in the 4 weeks preceding the first trial vaccination.
* History of major congenital defects or illness that require medical therapy, as determined by medical history or clinical assessment.
* History of any clinically significant chronic disease that in the opinion of the Investigator, might interfere with the evaluation of the study objectives.
* History of anaphylaxis, or any serious vaccine reaction, or hypersensitivity/allergy to any vaccine or components of study vaccine.
* Infants with known or suspected impairment of the immune function, or those receiving immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy or received immunosuppressive therapy prior to study entry
* Presence of evolving or changing neurological disorder or infant with a history of seizures and/or encephalopathy.
* Known thrombocytopenia or a bleeding disorder.
* Known personal or maternal history of HIV, Hepatitis B or Hepatitis C seropositivity.
* Planned surgery during the study.
* Receipt of blood or blood-derived products or immunoglobulins or planned administration during the trial which might interfere with the assessment of the immune response.
* Participation in another clinical trial 4 weeks preceding the trial enrolment or planned participation during the present trial period in another clinical trial.
* Infants whose families are planning to leave the area of the study site before the end of the study period.

Primary outcomes:
measure: Non-inferiority of SIIPL reduced IPV hexavalent vaccine in comparison with SIIPL HEXASIIL® vaccine.
timeFrame: 28 days post completion of 3-dose primary vaccination series in infants.
Secondary outcomes:
measure: Assessment of occurrence, severity, and relationship of adverse events (AEs)
timeFrame: Local and systemic solicited AEs occurring up to 7 days following each vaccination, unsolicited AEs and SAEs till 28 days post completion of a 3-dose primary vaccination series.
measure: Assessment of immunogenicity of SIIPL reduced IPV hexavalent vaccine with the comparator vaccine, SIIPL HEXASIIL® and to assess lot-to-lot consistency among 3 lots of SIIPL reduced IPV Hexavalent vaccine
timeFrame: 28 days post completion of the 3-dose primary vaccination series in infants.
Other outcomes:
measure: Pre- and post-booster safety of SIIPL reduced IPV hexavalent vaccine and comparator vaccine, SIIPL HEXASIIL® in toddlers.
timeFrame: Safety assessment from 28 days post completion of the 3-dose primary schedule till 28 days post booster.
measure: Pre- and post-booster immunogenicity of SIIPL reduced IPV hexavalent vaccine and comparator vaccine, SIIPL HEXASIIL® in toddlers.
timeFrame: Immunogenicity at prebooster and 28 days post booster dose between 12-24 months of age.
Locations:
city: Dhaka
country: Bangladesh
facility: International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B)
city: New Delhi
country: India
facility: Hamdard Institute of Medical Sciences and Research (HIMSR) with Centre for health research & Development, Society for applied studies, Hakeem Abdul Hameed Centenary Hospital (HAHCH)
state: Delhi
city: Mangalore
country: India
facility: Manipal Academy of Higher Education, Manipal
state: Karnataka
city: Mysore
country: India
facility: JSS Medical College and Hospital
state: Karnataka
city: Pune
country: India
facility: Bharati Vidyapeeth Medical College and Hospital, Pune
state: Maharashtra
city: Pune
country: India
facility: KEM Hospital and Research Centre, Vadu
state: Maharashtra
city: Chennai
country: India
facility: Sri Ramachandra Medical Centre, Chennai
state: Tamil Nadu
city: Kolkata
country: India
facility: Institute of Child Health, Kolkata
state: West Bengal
city: Chandigarh
country: India
facility: Post Graduate Institute of Medical Education and Research (PGIMER)
Study officials:
affiliation: KEM Hospital Research Centre, Pune, India
name: Anand Kawade
role: PRINCIPAL_INVESTIGATOR
affiliation: Bharati Vidyapeeth Medical College Hospital and Research Centre, Pune, India
name: Sonali Palkar
role: PRINCIPAL_INVESTIGATOR
affiliation: JSS Hospitla, Mysore, India
name: M D Ravi
role: PRINCIPAL_INVESTIGATOR
affiliation: Manipal Academy of Higher Education, Kasturba Medical College, Udipi and Karkala,India
name: Veena Kamat
role: PRINCIPAL_INVESTIGATOR
affiliation: Sri Ramchndra Institute of Higher Education and Research, Chennai, India
name: P Umapathy
role: PRINCIPAL_INVESTIGATOR
affiliation: Institute of Child Health, Kolkata, India
name: Kheya Ghosh
role: PRINCIPAL_INVESTIGATOR
affiliation: Post Graduate Institute of Medical Education and Research, Chandigarh, India
name: Madhu Gupta
role: PRINCIPAL_INVESTIGATOR
affiliation: Hamdard Institute of Medical Sciences and Research (HIMSR), New Delhi, India
name: Afreen khan
role: PRINCIPAL_INVESTIGATOR
affiliation: Yashwantrao Chavan Memorial Hospital, Pimpri, Pune, India
name: Deepali Ambike
role: PRINCIPAL_INVESTIGATOR
affiliation: International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh
name: K Zaman
role: PRINCIPAL_INVESTIGATOR
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