Phase 3a Randomized Study on Lot Consistency, Immunogenicity, and Safety of GSKVX000000025896 vs. Varicella Virus Oka/Merck Strain in Healthy Children
- Trial ID
- 2024-515869-33-00
- Protocol
- 213998 (VNS 20-002)
- Sponsor
- GlaxoSmithKline Biologicals
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to demonstrate the **consistency** of three manufacturing lots of the VNS vaccine in terms of seroresponse rate to **Varicella zoster virus** (VZV) at Day 43. Additionally, the study aims to demonstrate the consistency of these lots in terms of Geometric Mean Concentration (GMC) for antibodies to VZV at Day 43. Furthermore, the study seeks to establish the non-inferiority of the VNS vaccine (for the three pooled lots) compared with the varicella vaccine (VV) (for the two pooled lots) in terms of seroresponse rate and GMC for antibodies to VZV at Day 43. These objectives are clinically relevant as they assess the reliability and efficacy of the VNS vaccine in generating an immune response comparable to the existing VV, which is crucial for ensuring effective protection against varicella in the pediatric population.
Secondary objectives include:
- Demonstrating the non-inferiority of the VNS vaccine group compared with the VV group in terms of GMCs for antibodies to MMR viruses at Day 43.
- Evaluating the immunogenicity of the VNS vaccine compared with VV in terms of seroresponse rates for antibodies to MMR viruses at Day 43.
- Demonstrating the non-inferiority of the VNS vaccine group compared with the VV group in terms of GMC for antibodies to HAV at Day 43 (in HAV subset).
- Evaluating the immunogenicity of the VNS vaccine compared with VV in terms of seroresponse rates for antibodies to HAV at Day 43 (in HAV subset).
- Demonstrating the non-inferiority of the VNS vaccine group compared with the VV group in terms of GMCs for antibodies to **S. pneumoniae** (20 serotypes) at Day 43 [in Pneumococcal conjugate vaccine (PCV) subset].
- Demonstrating the non-inferiority of the VNS vaccine compared with VV in terms of adaptive seroresponse rate to VZV at Day 43.
- Evaluating the safety and reactogenicity following the administration of the VNS vaccine and VV when co-administered with MMR vaccine, HAV vaccine, and (if applicable) PCV.
Participants
The clinical trial involved a total of **1616 participants** who were healthy children aged between **12 to 15 months**. Both **male and female** subjects were included in the study. Participants were selected based on their health status, as established by medical history and clinical examination, ensuring they were healthy before entering the study. The trial population was specifically chosen from countries where the pneumococcal conjugate vaccine (PCV) is recommended at 12 to 15 months of age, and participants had previously received the primary series of PCV in the first year of life, with the last dose administered at least 60 days prior to study entry. The study focused on children who could comply with the protocol requirements, as determined by the investigator, and whose parents or legally acceptable representatives provided informed consent. The trial aimed to evaluate the consistency and non-inferiority of a new varicella vaccine compared to an existing one, with a focus on the seroresponse rate to the **Varicella zoster virus** at Day 43. The study did not specify any particular lifestyle considerations such as diet or physical activity for the participants.
Plans and Procedures
The clinical trial is designed as a **randomized**, observer-blind, controlled study to evaluate the **immunogenicity** and safety of an investigational varicella vaccine compared to an existing varicella vaccine, Varivax. The trial aims to demonstrate the consistency of three manufacturing lots of the investigational vaccine in terms of seroresponse rate and **geometric mean concentration** (GMC) for antibodies to the **Varicella zoster virus** (VZV) at Day 43. The study will involve healthy children aged 12 to 15 months, with the primary objective of assessing the non-inferiority of the investigational vaccine compared to Varivax.
The trial will commence with a screening visit to confirm eligibility based on inclusion criteria, such as age and health status, and to obtain informed consent from the participants' legally acceptable representatives. Following the screening, participants will be randomized to receive either the investigational vaccine or Varivax. The study will include several follow-up visits to monitor the participants' immune response and safety outcomes. The primary endpoint will be assessed at Day 43, with additional follow-up extending to Day 181 to evaluate any adverse events, including serious adverse events.
Participants are expected to be involved in the study for approximately six months, from the initial screening to the end-of-study visit. Conditions that may lead to early termination from the study include the occurrence of serious adverse events or non-compliance with the study protocol. The trial is estimated to conclude by August 2026, with recruitment starting in July 2025. The study will adhere to rigorous scientific and ethical standards to ensure the validity and reliability of the results.
Treatment
The clinical trial involves the administration of **VARIVAX®**, a varicella vaccine, which is a **suspension for injection**. The active substance in this vaccine is the **varicella virus Oka/Merck strain (live, attenuated)**, produced in human diploid (MRC-5) cells. This vaccine is provided as a powder and solvent for the preparation of an injection suspension in a prefilled syringe. The vaccine is administered subcutaneously at a dosage of 0.5 ml per dose. The maximum treatment period is one day, with a single administration. The vaccine is classified as a biological product and is not a pediatric formulation. The manufacturer of this vaccine is MSD Sharp & Dohme GmbH.
Another product used in the trial is an investigational varicella vaccine developed by GlaxoSmithKline Biologicals S.A. This vaccine is also a **suspension for injection** and contains the active substance identified as **GSKVX000000025896**. Similar to VARIVAX®, this investigational vaccine is administered subcutaneously at a dosage of 0.5 ml per dose, with a maximum treatment period of one day. The investigational vaccine is also classified as a biological product and is not a pediatric formulation. The investigational product is provided with a drug product diluent in a prefilled syringe, co-packed with a lyophilized drug product vial.
The trial aims to demonstrate the lot-to-lot consistency and evaluate the immunogenicity and safety of the investigational varicella vaccine compared to VARIVAX®. The study is designed to assess the seroresponse rate and geometric mean concentration of antibodies to the varicella-zoster virus at Day 43. The investigational vaccine is being tested for non-inferiority compared to the VARIVAX® vaccine in terms of these immunogenicity parameters.
Efficacy
The efficacy of the investigational varicella vaccine will be assessed through several primary and secondary endpoints. The primary endpoints include the **seroresponse** rate to Varicella Zoster Virus (VZV) anti-glycoprotein E (gE) Immunoglobulin (IgG) and the Geometric Mean Concentration (GMC) of anti-VZV gE IgG. These will be evaluated for three manufacturing lots of the VNS vaccine and compared with two pooled lots of the Varivax vaccine. The assessments will occur at Day 43 post-vaccination.
Secondary endpoints will further evaluate the immunogenicity by measuring GMCs and seroresponse rates for anti-measles, anti-mumps, anti-rubella, and anti-Hepatitis A antibodies. Additionally, the study will assess anti-S. pneumoniae serotype-specific Polysaccharide IgG antibody concentrations. Safety endpoints will include the percentage of participants reporting solicited administration site events, systemic events, and unsolicited adverse events. These will be monitored from Day 1 post-dose to various time points, including Day 43 and Day 181, to capture both immediate and longer-term responses.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Participant’s parent(s) Legally acceptable representatives /(LAR[s]), who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g., completion of the eDiaries, return for follow-up visits).
- Written or witnessed/thumb printed informed consent obtained from the participant’s parent(s)/LAR(s) prior to performance of any study-specific procedure.
- Healthy participants as established by medical history and clinical examination before entering into the study.
- A male or female between, and including, 12 to 15 months of age (i.e., from the day of 1-year birthday until the day before16 months of age) at the time of the administration of study interventions.
- Only for children in countries where PCV is recommended at 12 to 15 months of age as per national immunization schedule and provided as part of the study interventions: − Participant who previously received the primary series of PCV in the first year of life with last dose at least 60 days prior to study entry.
Exclusion Criteria
- History of any reaction or hypersensitivity likely to be exacerbated by any component of the study interventions.
- Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
- Hypersensitivity to latex.
- Major congenital defects, as assessed by the investigator.
- Recurrent history of uncontrolled neurological disorders or seizures.
- History of varicella disease.
- Active untreated tuberculosis
- Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study.
- Use of any investigational or non-registered product (drug, vaccine or invasive medical device) other than the study interventions during the period beginning 30 days before the dose of study interventions administration (Day -29 to Day 1), or their planned use during the study period.
- Planned administration of a vaccine in the period starting 30 days before the dose and ending 43 days after the dose of study interventions administration* (Visit 2) with the exception of inactivated influenza vaccine which may be given at any time during the study and administered at a different location than the study interventions. Any other age-appropriate vaccine may be given starting at Visit 2 and anytime thereafter. *If emergency mass vaccination for an unforeseen public health threat (e.g., a pandemic) is organized by public health authorities outside the routine immunization program, the time period described above can be reduced provided it is used according to the local governmental recommendations and sponsor is notified
- Chronic administration of immune-modifying drugs (defined as more than 14 consecutive days in total) and/or planned use of long-acting immune-modifying treatments at any time up to the end of the study. - Up to 90 days prior to the study intervention administration: − For corticosteroids, this will mean prednisone equivalent ≥0.5 mg/kg/day with maximum of 20 mg/day for pediatric participants. Inhaled and topical steroids are allowed. − Administration of immunoglobulins and/or any blood products or plasma derivatives. − Up to 180 days prior to study interventions administration: long-acting immune modifying drugs including among others immunotherapy (e.g., tumor necrosis factor-inhibitors), monoclonal antibodies (except the ones not interfering with the immune response to the study vaccines, e.g., nirsevimab), antitumoral medication.
- Previous vaccination against measles, mumps, and rubella.
- Previous vaccination against hepatitis A virus.
- Previous vaccination against varicella virus.
- Only for children in countries where PCV is recommended at 12 to 15 months of age as per national immunization schedule and provided as part of the study interventions, participant who previously received a booster dose of any PCV.
- Concurrently participating in another clinical study, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational intervention (drug/invasive medical device).
- Child in care
- Any study personnel’s immediate dependents, family, or household members.
- Participants with the following high-risk individuals in their household: - Immunocompromised individuals. - Pregnant women without documented history of varicella. - Newborn infants of mothers without documented history of varicella. - Newborn infants born less than (<) 28 weeks of gestation.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Recruiting | 14 Jul 2025 | 50 |
 Czechia | Recruiting | 14 Jul 2025 | 100 |
 Estonia | Recruiting | 14 Jul 2025 | 101 |
 Poland | Recruiting | 14 Jul 2025 | 50 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
VARIVAX® Pulver und Lösungsmittel zur Herstellung einer Injektionssuspension in einer Fertigspritze Varizellen-Lebendimpfstoff | Comparator | PULVER UND LÖSUNGSMITTEL ZUR HERSTELLUNG EINER INJEKTIONSSUSPENSION IN EINER FERTIGSPRITZE | SUBCUTANEOUS | 0.5 | 1 | PRD11373079 |
VARIVAX® Pulver und Lösungsmittel zur Herstellung einer Injektionssuspension in einer Fertigspritze Varizellen-Lebendimpfstoff | Comparator | PULVER UND LÖSUNGSMITTEL ZUR HERSTELLUNG EINER INJEKTIONSSUSPENSION IN EINER FERTIGSPRITZE | SUBCUTANEOUS | 0.5 | 1 | PRD4585484 |