A study on the immune response and safety of a combined measles, mumps, rubella, chickenpox vaccine compared to a marketed combined vaccine, given to healthy children 4 to 6 years of age

Overview

Sponsor-declared trial summary

Key facts

Sponsor

GlaxoSmithKline Biologicals, GlaxoSmithKline Biologicals

Participant type

Pediatric, Healthy volunteers

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

31 Jul 2023 → 20 Dec 2024

Decision date (initial)

2023-04-21

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

GlaxoSmithKline Biologicals SA

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Others, Prophylaxis

To evaluate the immune response to the MMRVNS vaccines (formulated with different potencies) and the MMRV vaccine (pooled group) in terms of geometric mean concentration (GMCs) for antibodies to measles, mumps, rubella, and varicella viruses.

Secondary objectives 2

1. To evaluate the immune response to the MMRVNS vaccines (formulated with different potencies) and the MMRV vaccine (pooled group) in terms of seroresponse rates for antibodies to measles, mumps, rubella, and varicella viruses.
2. To evaluate safety and reactogenicity following administration of the MMRVNS vaccines and the MMRV vaccine (pooled group).

Conditions and MedDRA coding

Healthy volunteers (prevention of measles, mumps, rubella and varicella infections)

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

EMA paediatric investigation plan (PIP)

EMEA-003341-PIP01-22

Plan to share IPD

Yes

IPD plan description

IPD for this study will be made available via the Clinical Study Data Request site. IPD will be made available within 6 months of publishing the results of the primary endpoints, a key secondary endpoints and safety data of the study.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Healthy participants as established by medical history and clinical examination before entering into the study.
2. A male or female between, and including, 4 years and 6 years of age (i.e., from 4-year birthday until the day before the 7-year birthday) at the time of study intervention administration, and in accordance with local regulations.
3. Participant who previously received a first dose of varicella-containing vaccine in the second year of life.
4. Participant who previously received a single dose of measles-, mumps-, rubella containing vaccine in the second year of life.
5. Written informed consent obtained from the participants’ parent(s)/legally acceptable representative(s) (LAR[s]) prior to performance of any study-specific procedure (participant informed assent will be obtained from participants in line with local rules and regulations).
6. Participants’ 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 electronic diaries [eDiaries], return for follow-up visits).

Exclusion criteria 19

1. History of any reaction or hypersensitivity likely to be exacerbated by any component of the study interventions including hypersensitivity to neomycin or gelatin.
2. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
3. Hypersensitivity to latex
4. Major congenital defects, as assessed by the investigator
5. History of measles, mumps, rubella, or varicella disease.
6. Recurrent history of or uncontrolled neurological disorders or seizures.
7. Acute disease at the time of enrollment. Acute disease is defined as the presence of a moderate or severe illness with or without fever. Fever is defined as body temperature ≥38.0°C (100.4 degrees Fahrenheit [°F]) by any age-appropriate route. All study interventions can be administered to participants with a minor illness such as diarrhea, mild upper respiratory infection without fever.
8. Participant with history of coronavirus disease 2019 (COVID-19) who is still symptomatic
9. Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study.
10. Use of any investigational or non-registered product (drug, vaccine, or medical device) other than the study interventions during the period beginning 30 days before the dose of study interventions (Day -29 to Day 1), or their planned use during the study period.
11. Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting 90 days prior to the study intervention administration. For corticosteriods, this will mean prednisone equivalent > 0.5 mg/kg/day or 20 mg/day whichever is the maximum dose for pediatric participants. Inhaled and topical steroids are allowed.
12. Administration of immunoglobulins and/or any blood products or plasma derivatives during the period starting 180 days before the dose of study interventions or planned administration during the study period.
13. Administration of long-acting immune-modifying drugs at any time during the study period (e.g., infliximab)
14. Previous vaccination with a second dose of varicella-containing vaccine or measles-, mumps-, rubella-containing vaccine.
15. Administration or planned administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the dose and ending at 43 days after the dose of study interventions administration* (Visit 3), with the exception of: − inactivated influenza (flu) vaccine which may be given at any time during the study and administered at a different location than the study interventions and, − routinely recommended licensed childhood DTPa-containing vaccines which can preferably be co-administered according to the local immunization practices of the participating country. Any other age-appropriate vaccine may be given starting at Visit 3 and anytime thereafter. *In case an emergency mass vaccination for an unforeseen public health threat (e.g., a pandemic) is recommended and/or organized by public health authorities outside the routine immunization program, the time period described above can be reduced if necessary for that vaccine, provided it is used according to the local government recommendations and that GSK/IQVIA is notified accordingly.
16. 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)
17. Child in care
18. Any study personnel's immediate dependents, family, or household members.
19. Participants with the following high-risk individuals in their household: − Immunocompromised individuals (as defined in Section 5.2.1). − Pregnant women without documented history of varicella. − Newborn infants of mothers without documented history of varicella. − Newborn infants born <28 weeks of gestation.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Anti-measles antibody geometric mean concentrations (GMCs) at Day 43.
2. Anti-mumps antibody geometric mean concentrations (GMCs ) at Day 43.
3. Anti-rubella antibody geometric mean concentrations (GMCs) at Day 43.
4. Anti-glycoprotein E (gE) antibody geometric mean concentrations (GMCs) at Day 43.

Secondary endpoints 9

1. Percentage of participants with seroresponse to anti-measles antibodies at Day 43.
2. Percentage of participants with seroresponse to anti-mumps antibodies at Day 43.
3. Percentage of participants with seroresponse to anti-rubella antibodies at Day 43.
4. Percentage of participants with seroresponse to varicella anti-gE antibodies at Day 43.
5. Percentage of participants reporting each solicited administration site event during the 4-day (day of administration and 3 following days) period after the administration of study interventions (administered at Day 1).
6. Percentage of participants reporting each solicited systemic event in terms of drowsiness and loss of appetite during the 4-day (day of administration and 3 following days) period after the administration of study interventions (administered at Day 1)
7. Percentage of participants reporting each solicited systemic event in terms of fever, measles/rubella-like rash, varicella-like rash and other rash (not measles/rubella-like rash or varicella-like rash) during the 43-day period (day of administration and 42 following days) after the administration of study interventions (administered at Day 1).
8. Percentage of participants reporting unsolicited adverse events (AEs) during the 43-day period (day of administration and 42 following days) after the administration of study interventions (administered at Day 1)
9. Percentage of participants reporting serious adverse events (SAEs) throughout the entire study period (From Day 1 to Day 181).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

GlaxoSmithKline Biologicals

Sponsor organisation

GlaxoSmithKline Biologicals

Address

Rue De L'Institut 89

City

Rixensart

Postcode

1330

Country

Belgium

GlaxoSmithKline Biologicals

Sponsor organisation

GlaxoSmithKline Biologicals

Address

Rue De L'institut 89

City

Rixensart

Postcode

1330

Country

Belgium

Scientific contact point

Organisation

GlaxoSmithKline Biologicals

Contact name

Clinical Disclosure Advisor

Public contact point

Organisation

GlaxoSmithKline Biologicals

Contact name

Clinical Disclosure Advisor

Third parties 5

Locations

2 EU/EEA countries · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 3 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications