A phase I, open label, clinical study to assess the safety and immunogenicity of indigenously developed liquid (DTwP-HepB-IPV-Hib) hexavalent combination vaccine in healthy toddlers aged 16–24 months

Abstract

This first in human study was designed as an open label clinical trial to assess the safety and immunogenicity of SIIPL DTwP-HepB-IPV-Hib (Hexavalent) combination vaccine in healthy toddlers, aged 16–24 months. A total of 24 healthy toddlers were administered a 0.5 ml single dose of SIIPL DTwP-HepB-IPV-Hib vaccine intramuscularly, and followed for 28 days for safety outcomes viz. immediate, solicited, unsolicited and serious adverse events. Blood samples were collected immediately prior to and 28 days after vaccination to assess the immunogenicity. Twenty four completed the study in compliance with the study protocol. None of the participants experienced any immediate or any serious adverse event. In terms of the frequency and intensity, the adverse events were comparable to DTwP-based combination vaccines. The vaccine elicited a strong booster response as demonstrated by a large increase in antibodies against all vaccine antigens. One month post booster vaccination seroprotection for diphtheria, tetanus, Hepatitis B, Haemophilus influenzae type b and polio virus type 1 and 3 was 100%. The percentage sero-response for pertussis was 75%. Four-fold increase in antibody concentration for pertussis was achieved in 87.5% subjects. Indigenously developed DTwP-HepB-IPV-Hib vaccine by Serum Institute of India Pvt. Ltd. was found to be safe, well tolerated and showed a robust immune response in toddlers. It was concluded that this vaccine should be assessed in the next phases of clinical development in the target population. Clinical Trial Registration – CTRI/2018/10/015875.

Evaluating the Compatibility of New Recombinant Protein Antigens (Trivalent NRRV) with a Mock Pentavalent Combination Vaccine Containing Whole-Cell Pertussis: Analytical and Formulation Challenges

“…Ltd. (New Delhi, India)). These vaccines contain 2-phenoxy ethanol (2-PE) as a preservative and utilize formaldehyde and heat as the wP bulk-inactivating agent [ 44 , 45 , 46 , 47 ]. Since developing countries vaccine manufacturers (DCVMs) are actively pursuing to replace TH-inactivated wP bulks with TH-free wP antigen bulks, more hexavalent vaccine candidates containing both wP and IPV in combination are now in the clinical development pipeline (e.g., from LG Life Sciences (Seoul, Republic of Korea) and Biologicals E. Limited (Telangana, India) [ 45 , 46 , 48 , 49 , 50 ]).…”

Single-arm clinical trials: design, ethics, principles

“…In the phase I clinical trials, single-arm trials are employed to investigate the mechanism of action, pharmacokinetic properties and safety of a new drug, providing foundational data for subsequent clinical trials. 15 The phase II trials aim to evaluate the efficacy and preliminary safety of a treatment and provide evidence for proceeding to a phase III trial. 16 Phase III trials typically involve large-scale RCTs designed to provide sufficient evidence to support the efficacy and safety of a new drug or treatment method.…”

A phase III randomized-controlled study of safety and immunogenicity of DTwP-HepB-IPV-Hib vaccine (HEXASIIL®) in infants

“…Safety and immunogenicity of this new vaccine was assessed in toddlers aged 16–24 months in a Phase I clinical study. The vaccine induced robust immune response and no safety concerns were observed 8 . The present Phase III study was conducted in infants following primary vaccination to demonstrate safety and immunogenic non-inferiority of DTwP-HepB-IPV-Hib vaccine to the licensed DTwP-HepB-Hib (Pentavac ® SD) and IPV (Poliovac ® ) vaccines in terms of serorotection/seroconversion rates.…”