Evaluation of Immunogenicity and Safety of Intramuscular GSKVX000000025896 and Priorix Versus Subcutaneous Varicella Virus Oka/Merck Strain in Healthy Children Aged 12-15 Months
- Trial ID
- 2024-518840-18-00
- Protocol
- 223105
- Sponsor
- GlaxoSmithKline Biologicals
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to demonstrate the **non-inferiority** of the intramuscular administration of the investigational varicella vaccine (VNS) compared to the subcutaneous administration of Varivax (VV) in terms of seroresponse rate to varicella-zoster virus (VZV) at Day 43. Additionally, the study aims to demonstrate the non-inferiority of the intramuscular administration of the measles, mumps, and rubella (MMR) vaccine compared to subcutaneous administration in terms of seroresponse rate to MMR at Day 43. These objectives are clinically relevant as they assess the efficacy of alternative administration routes, potentially offering more flexible vaccination strategies.
Secondary objectives include:
- Demonstrating an acceptable immune response for intramuscular administration of the MMR vaccine in terms of seroresponse rate to MMR at Day 43.
- Demonstrating the non-inferiority of intramuscular administration of the MMR vaccine compared to subcutaneous administration in terms of seroresponse rate to MMR at Day 43 with a reduced non-inferiority margin.
- Evaluating safety and reactogenicity following intramuscular administration of VNS and MMR vaccines, and subcutaneous administration of VV and MMR vaccines when co-administered with the hepatitis A virus (HAV) vaccine and, if applicable, the pneumococcal conjugate vaccine (PCV).
Participants
The clinical trial involves a total of **590 participants** who are healthy male and female infants aged between 12 to 15 months. The study population was selected based on specific inclusion criteria, ensuring that participants are in good health as determined by medical history and clinical examination. The trial focuses on children in countries where the pneumococcal conjugate vaccine (PCV) is recommended at this age, and participants must have completed the primary series of PCV in their first year of life, with the last dose administered at least 60 days prior to the study intervention. The trial aims to evaluate the non-inferiority of intramuscular administration of vaccines compared to subcutaneous administration in terms of seroresponse rate and geometric mean concentration (GMC) for antibodies. Participants' parents or legally authorized representatives (LARs) are required to comply with the study protocol, including the completion of electronic diaries and attendance at follow-up visits. The study addresses **varicella** as the medical condition of interest.
Plans and Procedures
The clinical trial is designed as a **randomized**, controlled study to evaluate the **immunogenicity** and safety of an investigational varicella vaccine and a marketed measles, mumps, and rubella (MMR) vaccine. The trial involves the administration of these vaccines either intramuscularly or subcutaneously to healthy children aged 12 to 15 months. The primary objective is to demonstrate the non-inferiority of the intramuscular administration of the varicella and MMR vaccines compared to their subcutaneous administration in terms of seroresponse rates and **geometric mean concentrations** (GMC) of antibodies at Day 43. The trial is expected to commence recruitment on September 1, 2025, and conclude by March 2, 2026.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, health status, and prior vaccination history. Following the initial administration of the study interventions, participants will return for follow-up visits to monitor safety and immunogenicity outcomes. The primary endpoints include seroresponse to varicella-zoster virus (VZV) and MMR antigens, as well as the concentration of specific **immunoglobulin G** (IgG) antibodies at Day 43. Secondary endpoints involve the assessment of solicited local and systemic adverse events, unsolicited adverse events, medically attended adverse events, and serious adverse events up to Day 181.
The expected duration of participant involvement is approximately six months, with the possibility of early termination if participants experience significant adverse events or if they are unable to comply with the study protocol. The trial will adhere to rigorous methodological standards, including randomization and control measures, to ensure the reliability and validity of the findings. The study will not involve any pediatric formulations, and the maximum daily dose for each vaccine is set at 0.5 ml. The trial will be conducted in compliance with ethical guidelines, with informed consent obtained from the parents or legally authorized representatives of the participants prior to any study-specific procedures.
Treatment
The clinical trial involves the administration of several vaccines, each with specific characteristics and administration protocols. The **experimental medication** in this trial is a vaccine developed by GlaxoSmithKline Biologicals S.A., identified by the sponsor product code GSKVx000000061721. This vaccine is formulated as a **suspension for injection** and is administered intramuscularly. The dosage is 0.5 ml per administration, with a maximum treatment period of one day. The vaccine is a structurally diverse substance classified as a biological product. It is co-packed with a drug product diluent in a prefilled syringe, which is used to reconstitute the lyophilized drug product vial before administration.
The trial also includes the use of **Priorix**, a vaccine produced by GlaxoSmithKline GmbH & Co. KG. Priorix is a **solution for injection** containing live, attenuated strains of measles, mumps, and rubella viruses. The measles virus is the Edmonston-Schwarz strain, the mumps virus is the RIT 4385 strain derived from the Jeryl Lynn strain, and the rubella virus is the Wistar RA 27/3 strain. This vaccine is administered subcutaneously at a dose of 0.5 ml, with a maximum treatment period of one day. It is also classified as a biological product and is provided in a prefilled syringe for ease of administration.
Another vaccine used in the trial is **Varivax**, produced by MSD Sharp & Dohme GmbH. Varivax is a **suspension for injection** containing the varicella virus Oka/Merck strain, which is live and attenuated. This vaccine is produced in human diploid (MRC-5) cells and is administered subcutaneously. The dosage is 0.5 ml, with a maximum treatment period of one day. Varivax is also classified as a biological product and is provided in a prefilled syringe for administration.
Throughout the trial, participant compliance with the dosing schedule is monitored to ensure accurate administration and data collection. The trial aims to evaluate the immunogenicity and safety of these vaccines when administered to healthy children aged 12 to 15 months, comparing intramuscular and subcutaneous routes of administration. The primary objective is to demonstrate the non-inferiority of the intramuscular administration of the investigational varicella vaccine compared to the subcutaneous administration of Varivax, as well as the non-inferiority of the intramuscular administration of the MMR vaccine compared to its subcutaneous administration.
Efficacy
The efficacy of the investigational varicella vaccine and Priorix will be assessed in a Phase 3a, open-label, randomized, controlled study. The primary endpoints for evaluating efficacy include the **seroresponse** to varicella-zoster virus (VZV) glycoprotein E (gE) and the concentration of anti-VZV gE IgG at Day 43. Additionally, the seroresponse to measles, mumps, and rubella (MMR) antigens and the concentration of anti-measles, anti-mumps, and anti-rubella IgG at Day 43 will be measured. These endpoints will be used to demonstrate the non-inferiority of intramuscular administration compared to subcutaneous administration.
Secondary endpoints include the percentage of participants reporting solicited administration site events such as injection site redness, pain, and swelling within 4 days post-dose, as well as systemic events like drowsiness, loss of appetite, and irritability within 15 days post-dose. The study will also monitor for fever within 22 days post-dose and various types of rashes within 43 days post-dose. Unsolicited adverse events, medically attended adverse events, and serious adverse events will be recorded from Day 1 post-dose up to the study end on Day 181. The efficacy assessments will be conducted using validated laboratory tests and patient-reported outcomes at specified timepoints, ensuring a comprehensive evaluation of the vaccine's performance.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Participant’s parent(s)/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 before 16 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 the administration of study intervention.
Exclusion Criteria
- History of any reaction or hypersensitivity likely to be exacerbated by any component of the study interventions including hypersensitivity to neomycin or gelatin.
- Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
- Hypersensitivity to latex.
- Major congenital defects, as assessed by the investigator.
- Recurrent history of uncontrolled neurological disorders or seizures.
- History of measles, mumps, rubella, or varicella disease.
- Active untreated tuberculosis.
- Participants with bleeding disorders (e.g., thrombocytopenia or any coagulation disorder).
- Condition that in the judgment of the investigator would make intramuscular injection unsafe.
- 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.
- 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 varicella virus.
- Previous vaccination against hepatitis A 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)
- Any study personnel or their immediate dependents, family, or household members.
- Child in care. Please see DEFINITIONS OF TERMS for the definition of child in care.
- 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 <28 weeks of gestation.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Yet Recruiting | 01 Sept 2025 | 17 |
 Bulgaria | Not Recruiting | 01 Sept 2025 | 23 |
 Denmark | Not Yet Recruiting | 01 Sept 2025 | 50 |
 Estonia | Recruiting | 01 Sept 2025 | 74 |
 Greece | Not Yet Recruiting | 01 Sept 2025 | 40 |
 Lithuania | Not Yet Recruiting | 01 Sept 2025 | 40 |
 Poland | Recruiting | 01 Sept 2025 | 90 |
 Romania | Recruiting | 01 Sept 2025 | 20 |
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 |
|---|---|---|---|---|---|---|
Priorix - Pulver und Lösungsmittel zur Herstellung einer Injektionslösung in einer Fertigspritze|Masern-Mumps-Röteln-Lebendimpfstoff | Test | PULVER UND LÖSUNGSMITTEL ZUR HERSTELLUNG EINER INJEKTIONSLÖSUNG IN EINER FERTIGSPRITZE | INTRAMUSCULAR | 0.5 | 1 | PRD11663547 |
Priorix - Pulver und Lösungsmittel zur Herstellung einer Injektionslösung in einer Fertigspritze|Masern-Mumps-Röteln-Lebendimpfstoff | Comparator | PULVER UND LÖSUNGSMITTEL ZUR HERSTELLUNG EINER INJEKTIONSLÖSUNG IN EINER FERTIGSPRITZE | SUBCUTANEOUS | 0.5 | 1 | PRD11663545 |
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 |
Priorix - Pulver und Lösungsmittel zur Herstellung einer Injektionslösung in einer Fertigspritze|Masern-Mumps-Röteln-Lebendimpfstoff | Test | PULVER UND LÖSUNGSMITTEL ZUR HERSTELLUNG EINER INJEKTIONSLÖSUNG IN EINER FERTIGSPRITZE | INTRAMUSCULAR | 0.5 | 1 | PRD11663546 |
Priorix - Pulver und Lösungsmittel zur Herstellung einer Injektionslösung in einer Fertigspritze|Masern-Mumps-Röteln-Lebendimpfstoff | Test | PULVER UND LÖSUNGSMITTEL ZUR HERSTELLUNG EINER INJEKTIONSLÖSUNG IN EINER FERTIGSPRITZE | INTRAMUSCULAR | 0.5 | 1 | PRD7793720 |
Priorix - Pulver und Lösungsmittel zur Herstellung einer Injektionslösung in einer Fertigspritze
Masern-Mumps-Röteln-Lebendimpfstoff | Comparator | PULVER UND LÖSUNGSMITTEL ZUR HERSTELLUNG EINER INJEKTIONSLÖSUNG IN EINER FERTIGSPRITZE | SUBCUTANEOUS | 0.5 | 1 | PRD344350 |