Evaluation of Immunogenicity and Safety of GSKVX000000025896 Compared to Varicella Virus Oka/Merck Strain in Healthy Pediatric Subjects
- Trial ID
- 2024-516635-27-00
- Protocol
- 214002 (VNS 20-004)
- Sponsor
- GlaxoSmithKline Biologicals
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to assess the **non-inferiority** of the immune response elicited by two doses of the investigational varicella (VNS) vaccine compared to two doses of the Varivax (VV) vaccine. This evaluation focuses on the seroresponse rate to the **Varicella zoster virus (VZV)** at Day 43 following the second dose. Additionally, the study aims to compare the Geometric Mean Concentration (GMC) for VZV at the same time point. The clinical relevance of this objective lies in determining whether the investigational vaccine can provide an immune response that is not inferior to the established Varivax vaccine, which is crucial for ensuring effective protection against varicella in pediatric populations.
Secondary objectives include:
- Evaluating the immune response of a second dose of the VNS vaccine following a first dose of VV in terms of seroresponse rate and GMC for VZV at Day 43 post-Dose 2.
- Assessing the safety and reactogenicity following the administration of each dose of the VNS vaccine and VV in different study groups when co-administered with measles, mumps, and rubella (MMR) vaccine, hepatitis A virus (HAV) vaccine, and, if applicable, pneumococcal conjugate vaccine (PCV).
Participants
The clinical trial involves a total of **521 participants** who are being evaluated for their immune response to a varicella vaccine. The study population consists of both **male and female** subjects, specifically healthy children aged **12 to 15 months**. Participants were selected based on their ability to comply with the study protocol, as determined by their parent(s) or legally acceptable representative(s). The trial includes children from countries where the pneumococcal conjugate vaccine (PCV) is recommended at this age, and who have completed the primary series of PCV in their first year of life, with the last dose administered at least 60 days prior to study entry. The participants are considered a vulnerable population due to their young age. The study does 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**, and **controlled** study to evaluate the **immunogenicity** and safety of an investigational varicella vaccine compared to Varivax when administered as a second dose to healthy children. The trial aims to assess the non-inferiority of the immune response of two doses of the investigational varicella vaccine compared to two doses of the Varivax vaccine in terms of seroresponse rate and **geometric mean concentration** for **Varicella zoster virus** at Day 43 post the second dose. The study is expected to commence recruitment on July 15, 2025, and conclude by December 16, 2026.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, health status, and prior vaccination history. The inclusion visit will ensure that participants are healthy, aged between 12 to 15 months, and have received the primary series of **pneumococcal conjugate vaccine** if applicable. Following the initial dose, participants will return for a second dose three months later. Follow-up visits will be conducted to monitor the immune response and any adverse events, with specific time frames for solicited administration site and systemic events. The end-of-study visit will occur on Day 271, marking the completion of the participant's involvement in the trial.
The expected duration of participant involvement is approximately nine months, from the first dose to the end-of-study visit. Conditions that may lead to early termination from the study include non-compliance with the protocol, withdrawal of consent by the participant's parent or legally acceptable representative, or any adverse event that, in the opinion of the investigator, warrants discontinuation for the safety of the participant. The trial 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 two experimental medications, both of which are **biological** vaccines intended for the prevention of varicella. The first experimental medication is the **VARIVAX®** vaccine, which is a **suspension for injection** containing the **varicella virus Oka/Merck strain (live, attenuated)**. This vaccine is provided as a powder and solvent for the preparation of an injection suspension in a pre-filled syringe. The maximum daily dose is 0.5 ml, administered subcutaneously, with a maximum treatment period of one day. The vaccine is not a pediatric formulation and is produced by MSD Sharp & Dohme GmbH. The administration of this vaccine is intended to evaluate its immunogenicity and safety when given as a second dose to healthy children.
The second experimental medication is another formulation of the **VARIVAX®** vaccine, which also serves as a **suspension for injection**. This formulation contains the **varicella virus Oka/Merck strain, (live, attenuated) produced in human diploid (MRC-5) cells**. Similar to the first formulation, it is provided as a powder and solvent for the preparation of an injection suspension in a pre-filled syringe. The dosage and administration route are identical, with a maximum daily dose of 0.5 ml administered subcutaneously, and a maximum treatment period of one day. This formulation is also not a pediatric formulation and is produced by MSD Sharp & Dohme GmbH. The trial aims to compare the immune response of this formulation to the investigational vaccine.
The investigational vaccine, identified by the sponsor product code **GSKVx000000061721**, is a **suspension for injection** containing the active substance **GSKVX000000025896**. This vaccine is also a **biological** product and is produced by GlaxoSmithKline Biologicals S.A. The investigational vaccine is administered subcutaneously with a maximum daily dose of 0.5 ml and a maximum treatment period of one day. The investigational vaccine is being evaluated for its immunogenicity and safety when given as a second dose to healthy children, in comparison to the VARIVAX® vaccine formulations.
Throughout the trial, participant compliance with the dosing schedule will be monitored to ensure accurate assessment of the vaccine's efficacy and safety. The trial's main objective is to evaluate the non-inferiority of the immune response of two doses of the investigational vaccine compared to two doses of the VARIVAX® vaccine in terms of seroresponse rate and geometric mean concentration for the **varicella zoster virus (VZV)** at Day 43 post-Dose 2.
Efficacy
The efficacy of the investigational varicella vaccine will be assessed by evaluating the **seroresponse** rate and the **Geometric Mean Concentration (GMC)** of anti-Varicella Zoster Virus (VZV) glycoprotein E (gE) IgG antibodies. The primary endpoints include the percentage of participants with a seroresponse to VZV gE IgG and the GMC of anti-VZV gE IgG for two doses of the investigational varicella vaccine compared to two doses of the Varivax vaccine. These measurements will be taken at Day 133, which is 43 days post the second dose.
Secondary endpoints will further evaluate the seroresponse and GMC in a group receiving a combination of Varivax and the investigational vaccine. Additionally, the trial will monitor the percentage of participants reporting solicited administration site and systemic events, as well as unsolicited adverse events (AEs) and medically attended adverse events (MAAEs) over specified time frames. The schedule for these assessments includes various time points, such as Day 1 to Day 4, Day 91 to Day 94, and up to Day 271 for serious adverse events (SAEs). The data collection will involve validated laboratory tests and patient-reported outcomes to ensure comprehensive evaluation of the vaccine's efficacy.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Participant’s parent(s)/Legally acceptable representative (LAR)(s), who, in the opinion of the investigator, can and will comply with the requirements of the protocol
- 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 the first 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.
- Planned administration of a vaccine in the period starting 30 days before the first dose and ending 43 days after the second dose of study interventions administration* (Visit 3), 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.
- 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 immunemodifying 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).
- 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 first dose of study interventions (Day -29 to Day 1), or their planned use during the study period.
- Child in care.
- Any study personnel’s immediate dependents, family, or household members.
- Participants with the following high-risk individuals in their household: i) Immunocompromised individuals. ii) Pregnant women without documented history of varicella. iii) Newborn infants of mothers without documented history of varicella. iv) Newborn infants born less than (<) 28 weeks of gestation.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Denmark | Not Yet Recruiting | 15 Jul 2025 | 61 |
 Norway | Not Yet Recruiting | 15 Jul 2025 | 18 |
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 |