Investigational Vaccine for Chickenpox

Recruiting at 38 trial locations

Overseen By EU GSK Clinical Trials Call Center

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: GlaxoSmithKline

Must not be taking: Immune-modifying drugs, Corticosteroids

Disqualifiers: Immunosuppressive conditions, Neurological disorders, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The purpose of this study is to assess how well-tolerated GSK's investigational varicella vaccine (VNS Vaccine) is, in comparison to an already approved varicella vaccine (VV) known as Varivax. The study will be conducted on healthy children aged 12 to 15 months, and who have neither contracted varicella nor received a varicella vaccination.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking current medications, but it does exclude participants using certain immune-modifying drugs or investigational products within specific time frames before the study. It's best to discuss your current medications with the study team to see if they affect your eligibility.

What data supports the effectiveness of the investigational varicella vaccine treatment for chickenpox?

Research shows that the varicella vaccine is effective in preventing chickenpox, with one study indicating it was 84.5% effective in preventing all cases and 100% effective in preventing severe cases. Additionally, it has been successfully used in immunocompromised children, like those with leukemia, with full immunization observed in seronegative patients. ^{1 2 3 4 5}

Is the investigational varicella vaccine generally safe for humans?

The varicella vaccine has been widely used and studied, with serious side effects being rare. Most reported side effects are mild, like injection site reactions, and the vaccine is considered safe for most people, although those with certain health conditions may experience more serious effects. ^{6 7 8 9 10}

How is the investigational varicella vaccine different from other treatments for chickenpox?

The investigational varicella vaccine is unique because it is a live attenuated vaccine, meaning it uses a weakened form of the virus to stimulate the immune system without causing the disease. This approach is different from antiviral drugs like acyclovir, which are used to treat severe complications in high-risk groups, and from zoster hyperimmunoglobulin, which provides protection during the incubation period. ^{3 11 12 13 14}

Eligibility Criteria

This trial is for healthy children aged 12 to 15 months who have never had chickenpox or the chickenpox vaccine. They must not have received any other vaccines within four weeks before the study starts and should not be planning to receive any during the study.

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 the study

Exclusion Criteria

I have had chickenpox in the past.

Previous vaccination against measles, mumps, and rubella

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)

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive 1 dose of either the investigational VNS vaccine or the marketed VV, along with MMR, HAV, and PCV vaccines on Day 1

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness, including reporting of systemic events and adverse events

26 weeks

Treatment Details

Interventions

• Investigational varicella vaccine (Cancer Vaccine)

Trial Overview The trial is testing a new investigational varicella (chickenpox) vaccine against an already approved one, Varivax. It will compare how well each vaccine works and how safe they are when given to young children.

Participant Groups

Group I: VNS Group Experimental Treatment 6 Interventions

Participants receive 1 dose of a VNS vaccine, 1 dose of measles, mumps, and rubella (MMR) vaccine, 1 dose of hepatitis A (HAV) vaccine, and 1 dose of PCV (either PCV 13 or Vaxneuvance or PCV 20) on Day 1.

Group II: VV Group Active Control 6 Interventions

Participants receive 1 dose of a marketed VV, 1 dose of MMR vaccine, 1 dose of HAV vaccine, and 1 dose of PCV (either PCV 13 or Vaxneuvance or PCV 20) on Day 1.

Who Is Running the Clinical Trial?

GlaxoSmithKline

Lead Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Findings from Research

In a trial involving 37 leukemic children, the live attenuated OKA varicella vaccine successfully fully immunized all 20 seronegative patients, demonstrating its efficacy in this vulnerable population.

The vaccine was well-tolerated with only a few side effects and no cases of generalized vaccinal infection, suggesting it is a safe option for immunocompromised patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study of tolerance and effectiveness of a varicella vaccine in leukemic children. Bancillon, A., Leblanc, T., Baruchel, A., et al.[2007]

The varicella vaccine used as post-exposure prophylaxis (PEP) for chickenpox in pediatric patients is cost-effective, saving an average of USD 611 per patient while also reducing the quality-adjusted life-year (QALY) loss compared to not using the vaccine.

In a decision analysis involving local epidemiology and medical literature, the study found that PEP with the varicella vaccine resulted in lower costs (USD 320 vs USD 731) and less QALY loss (0.00423 vs 0.01122) when compared to no PEP, demonstrating its effectiveness in preventing chickenpox after exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness analysis of varicella vaccine as post-exposure prophylaxis in Hong Kong. Chui, KS., Wu, HL., You, JH.[2013]

The live attenuated varicella vaccine demonstrated an efficacy of 87.1% in preventing varicella in a study of 5997 children aged 1 to 12 years, with only six cases in the vaccine group compared to 46 in the placebo group.

The vaccine was found to be safe, with no significant difference in adverse reactions between the vaccine and placebo groups, and a high seroconversion rate of 97.1%, indicating strong immune response in vaccinated children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, safety and immunogenicity of live attenuated varicella vaccine in healthy children in China: double-blind, randomized, placebo-controlled clinical trial. Hao, B., Chen, Z., Zeng, G., et al.[2019]

The varicella vaccine (Varivax) is 84.5% effective in preventing all cases of chickenpox when given before exposure, and it is 100% effective in preventing severe cases, based on a review of 19 studies.

When given after exposure to the virus, the varicella vaccine is also highly effective in preventing or reducing the severity of the disease, but a two-dose schedule is now recommended to improve effectiveness and prevent outbreaks in high-contact environments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Varicella vaccine effectiveness in the US vaccination program: a review. Seward, JF., Marin, M., Vázquez, M.[2022]

In a study of 181 healthy children vaccinated with a reformulated varicella vaccine, the overall seroconversion rate was 99%, indicating high efficacy of the vaccine.

Risk factors for breakthrough varicella included being vaccinated at 14 months or younger, having household contact with varicella, and receiving a low titre vaccine, which suggests that vaccination strategies may need to be adjusted to reduce these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk factors for breakthrough varicella in healthy children. Lim, YJ., Chew, FT., Tan, AY., et al.[2019]

Between 1995 and 2005, nearly 48 million doses of the varicella vaccine were distributed, with 25,306 adverse events reported, indicating a low incidence of serious adverse events at 2.6 per 100,000 doses.

While some adverse events, such as meningitis, were linked to the vaccine strain of varicella-zoster virus, serious complications remain rare and are outweighed by the significant benefits of vaccination, highlighting the importance of ongoing safety monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of varicella vaccine after licensure in the United States: experience from reports to the vaccine adverse event reporting system, 1995-2005. Chaves, SS., Haber, P., Walton, K., et al.[2022]

In a study of over 1.1 million children who received the varicella vaccine, there was no significant increase in the risk of serious adverse events like idiopathic thrombocytopenic purpura (ITP), meningitis, encephalitis, or ischemic stroke following vaccination.

A slight increase in the risk of pneumonia was observed during the 6th week post-vaccination, but this was not seen for other serious conditions, indicating that the varicella vaccine is generally safe with minimal risk of severe side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of pre-specified adverse events following varicella vaccine: A population-based self-controlled risk interval study. Liu, CH., Yeh, YC., Huang, WT., et al.[2021]

The live-virus varicella vaccine (Varivax) was licensed in 1995 and initially showed minimal adverse events, but rare risks have been identified since its widespread use.

A case study of an HIV-infected boy revealed that he developed a severe reaction, including dissemination of the vaccine strain of varicella zoster, highlighting potential risks in immunocompromised individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Disseminated vaccine strain varicella as the acquired immunodeficiency syndrome-defining illness in a previously undiagnosed child. Kramer, JM., LaRussa, P., Tsai, WC., et al.[2019]

Varilrix, the first refrigerator-stable varicella vaccine, has been used safely and effectively in over 10,000 individuals across clinical trials and mass vaccination programs, demonstrating its immunogenicity and efficacy against chickenpox.

With 16 years of clinical and postmarketing experience, Varilrix is indicated for high-risk groups and healthy individuals, highlighting its importance in preventing varicella in various populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sixteen years of global experience with the first refrigerator-stable varicella vaccine (Varilrix). Kreth, HW., Lee, BW., Kosuwon, P., et al.[2019]

The VAR-PE process for the varicella vaccine demonstrated 100% seroconversion in healthy children aged 12 to 23 months, showing that it is as effective as the commercial varicella vaccine (VAR) in inducing an immune response.

While both vaccines had similar rates of injection-site adverse events, VAR-PE was associated with higher instances of pyrexia and otitis media, indicating some differences in safety profiles, but overall, the incidence of adverse events decreased after the second dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind, randomized, multicenter, controlled study to evaluate the immunogenicity, safety, and tolerability of varicella vaccine (VARIVAX™) passage extension 34 (PE34) process administered concomitantly with measles, mumps, and rubella vaccine (M-M-R™ II). Silas, PE., Zissman, EN., Gardner, J., et al.[2021]

The varicella vaccine is effective in preventing chickenpox in immunocompromised children, such as those with acute leukemia or solid tumors, and also benefits healthy seronegative siblings.

Acyclovir, an antiviral drug, effectively reduces severe complications from chickenpox in at-risk groups, and the use of zoster hyperimmunoglobulin provides additional protection during the incubation period, suggesting that with these interventions, chickenpox will become less of a medical concern even for vulnerable populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Results of virostatic treatment of varicella with various severity]. Stary, A.[2013]

In a study of 505 healthy children aged 1 to 12 years, the thermostable varicella vaccine was found to be well tolerated, with most side effects being mild and temporary, resolving within the follow-up period.

Only two subjects experienced severe symptoms, but no serious adverse events were reported, indicating a strong safety profile for the vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reactogenicity to a live attenuated varicella vaccine in Canadian children. Diaz-Mitoma, F., Halperin, SA., Scheifele, D.[2020]

Children who experienced breakthrough varicella after being vaccinated had significantly fewer total and vesicular lesions compared to those with natural varicella, indicating a milder form of the disease.

Breakthrough varicella was associated with a lower incidence of fever and a shorter duration of illness, suggesting that the live attenuated vaccine effectively modifies the clinical severity of chickenpox.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical survey of natural varicella compared with breakthrough varicella after immunization with live attenuated Oka/Merck varicella vaccine. Bernstein, HH., Rothstein, EP., Watson, BM., et al.[2010]

The Advisory Committee on Immunization Practices (ACIP) has issued its first recommendations for the use of the live, attenuated varicella virus vaccine (VARIVAX), which is approved for healthy individuals aged 12 months and older.

These recommendations also update previous guidelines on the use of varicella zoster immune globulin (VZIG) for preventing chickenpox, highlighting the importance of vaccination in managing varicella outbreaks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention of varicella: Recommendations of the Advisory Committee on Immunization Practices (ACIP). Centers for Disease Control and Prevention. [2017]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Study of tolerance and effectiveness of a varicella vaccine in leukemic children. [2007]

2. England pubmed.ncbi.nlm.nih.gov

Cost-effectiveness analysis of varicella vaccine as post-exposure prophylaxis in Hong Kong. [2013]

3. England pubmed.ncbi.nlm.nih.gov

Efficacy, safety and immunogenicity of live attenuated varicella vaccine in healthy children in China: double-blind, randomized, placebo-controlled clinical trial. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Varicella vaccine effectiveness in the US vaccination program: a review. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Risk factors for breakthrough varicella in healthy children. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Safety of varicella vaccine after licensure in the United States: experience from reports to the vaccine adverse event reporting system, 1995-2005. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Assessment of pre-specified adverse events following varicella vaccine: A population-based self-controlled risk interval study. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Disseminated vaccine strain varicella as the acquired immunodeficiency syndrome-defining illness in a previously undiagnosed child. [2019]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Sixteen years of global experience with the first refrigerator-stable varicella vaccine (Varilrix). [2019]

10. United States pubmed.ncbi.nlm.nih.gov

A double-blind, randomized, multicenter, controlled study to evaluate the immunogenicity, safety, and tolerability of varicella vaccine (VARIVAX™) passage extension 34 (PE34) process administered concomitantly with measles, mumps, and rubella vaccine (M-M-R™ II). [2021]

11. Germany pubmed.ncbi.nlm.nih.gov

[Results of virostatic treatment of varicella with various severity]. [2013]

12. Canada pubmed.ncbi.nlm.nih.gov

Reactogenicity to a live attenuated varicella vaccine in Canadian children. [2020]

13. United States pubmed.ncbi.nlm.nih.gov

Clinical survey of natural varicella compared with breakthrough varicella after immunization with live attenuated Oka/Merck varicella vaccine. [2010]

14. United States pubmed.ncbi.nlm.nih.gov

Prevention of varicella: Recommendations of the Advisory Committee on Immunization Practices (ACIP). Centers for Disease Control and Prevention. [2017]