To determine if the Shingrix vaccine is immunogenic for people living with HIV who are aged 50 and over or have perinatally acquired HIV infection and are aged 18 or over

Plain English Summary

Background and study aims
People living with HIV have a higher risk of developing Herpes Zoster infection (otherwise known as Shingles), than other age-matched populations. Being aged over 60 years is a risk factor for the general population, but people living with HIV are not eligible to be vaccinated against Shingles until they are 70 years old. People living with HIV may have less protection from infections and have more associated illnesses or infections than the general population. Studies involving other vaccines have shown that people living with HIV have a less robust response to vaccination than people without HIV.
HZ/Su (SHINGRIX) is the first vaccine of this type developed to protect against shingles and is licensed for use in the USA and the EU, among other regions. The efficacy against and immune responses to Shingles is durable and suggests that the clinical benefit in older adults is sustained for at least 7 years after vaccination. Data in all age groups and in HIV-infected people for the SHINGRIX vaccine is limited. From July 2021, the vaccine has been approved for use in immunocompromised people aged 18 and over and this includes individuals with HIV infection.
This trial addresses the question of, does the Shingrix vaccine produce an immune response in people living with HIV, who are either 50 years and over or adults who acquired HIV at birth.

Who can participate?
People living with HIV aged 50 years and over and adults aged 18 years and over who acquired HIV at birth

What does the study involve?
Participants will receive an initial dose of the vaccine followed by a second dose 2 months later. Participants will be on the trial for a total of 48 weeks and have blood samples taken at 3-month intervals to check their immune response to the vaccine. Any participant who has suspected Shingles will have a swab taken for analysis and treated clinically.

What are the possible benefits and risks of participating?
This trial is relevant to people living with HIV as the vaccine is not currently within UK treatment guidelines for these people. This trial will inform the guidelines regarding whether it should be included for these two groups. The possible benefits of participating in this trial are that participants will get a shingles vaccine sooner than they would according to UK guidelines. The information collected in this trial may help inform vaccine guidelines for people living with HIV.
There is a potential for some discomfort and bruising at the blood sample site. Staff are all trained and experienced in venepuncture, so this should be minimal. The quantity of blood being taken is above that of standard of care, but participants will be seated on a reclinable clinic couch and refreshments will be made available, to minimize the likelihood of light-headedness or other side effects as a result of blood taking.
There is a potential for discomfort, redness and/or some swelling at the vaccination site. After vaccination, participants will be monitored for 15 minutes to assess any vaccine reactions or side effects and address them accordingly. Delegated research staff will be trained and experienced in giving vaccinations. Adverse events, including any reactions to vaccination, will be monitored throughout the trial. The participant information sheet contains information about potential side effects of the vaccine and participants will have the opportunity to discuss with the trial investigator both before enrolling and throughout the trial. Any individual who has had an allergic reaction to any vaccine in the past will be excluded from the trial.
The number of research visits are above that of standard of care, however, participants will be reimbursed for their time and travel. The window periods for each visit are long enough to arrange a convenient appointment for the participant, limiting inconvenience and burden. Other than four additional visits to what they would routinely experience over the trial period, there are no additional lifestyle changes required.
In addition to the above, all routine clinic support services will be made available to participants throughout the trial, should they require them.
The survey comprises five brief questions regarding the participant's knowledge of shingles and shingles vaccines. No sensitive questions will be asked.

Where is the study run from?
Guy's and St Thomas' NHS Foundation Trust (UK)

When is the study starting and how long is it expected to run for?
September 2023 to May 2025

Who is funding the study?
GlaxoSmithKline (UK)

Who is the main contact?
Dr Julie Fox, Julie.fox@kcl.ac.uk

Study website

Type

Scientific

Contact name

Dr Amy Holton

ORCID ID

Contact details

16th Floor
Tower Wing
Guy's Hospital
Great Maze Pond
London
SE1 9RT
United Kingdom
+44 (0)7703469925
amy.holton@kcl.ac.uk

Type

Scientific

Contact name

Dr Julie Fox

ORCID ID

Contact details

2nd Floor
Southwark Wing
Guy's Hospital
Great Maze Pond
London
SE1 9RT
United Kingdom
+44 (0)20 71887188
julie.fox@kcl.ac.uk

Type

Principal Investigator

Contact name

Dr Julie Fox

ORCID ID

Contact details

Guy's Hospital
Great Maze Pond
London
SE1 0RT
United Kingdom
+44 (0)20 71887188
julie.fox@kcl.ac.uk

EudraCT/CTIS number

Nil known

IRAS number

1004647

ClinicalTrials.gov number

Nil known

Protocol/serial number

3636 - SAGE, IRAS 1004647

Scientific title

The immunogenicity of Shingrix vaccination in people living with HIV at risk of shingles infection (SAGE)

Acronym

SAGE

Study hypothesis

Primary objectives:
To determine if the Shingrix vaccine is immunogenic for people living with HIV who are aged 50 years and over OR have perinatally acquired HIV infection and are aged 18 years and over.

Secondary objectives:
1. Detailed characterization of cell-mediated and humoral responses to the candidate vaccine
2. Impact of current CD4, nadir CD4, CD4: CD8 on immunogenicity.
3. Impact of vaccination on HIV reservoirs.
4. To explore BCR and TCR repertoires in response to vaccination.
5. To investigate the sequences of viruses from individuals who develop shingles after vaccination.
6. To assess the safety of the Shingrix vaccine in people living with HIV aged above 50 years and those born with HIV, who are 18 years and over.

Ethics approval(s)

Ethics approval not required

Ethics approval additional information

Approved 11/12/2023, Wales REC 2 (Health and Care Research Wales, Castlebridge 5, 15-19 Cowbridge Road East, Cardiff, CF11 9AB, United Kingdom; +44 (0)2922941119; Wales.REC2@wales.nhs.uk), ref: 23/WA/0283

Study design

Open-label single-arm interventional trial

Primary study design

Interventional

Secondary study design

Non randomised study

Study setting(s)

Hospital

Study type

Prevention

Patient information sheet

Not available in web format, please use the contact details to request a participant information sheet

Condition

Herpes zoster (shingles) in people living with HIV

Intervention

This is an open-label, single-arm, interventional trial involving HZ/Su (SHINGRIX), with a vaccination schedule consisting of two doses of 0.5 ml each: an initial dose followed by a second dose 2 months later.

Intervention type

Drug

Pharmaceutical study type(s)

Not Applicable

Phase

Phase IV

Drug/device/biological/vaccine name(s)

Shingrix powder and suspension for suspension for injection, Herpes zoster vaccine [varicella-zoster virus]

Primary outcome measure

1. Total VZV-specific cell-mediated response measured using ELISPOT in peripheral blood mononuclear cells (PBMCs) from baseline to week 12 (4 weeks after the second vaccine dose)
2. Total VZV-specific antibody measured using ELISA in plasma from baseline to week 12 (4 weeks after the second vaccine dose)

Secondary outcome measures

1. Evolution of VZV-specific cell-mediated response over the study period, measured at baseline (first vaccine dose), week 4, week 8, week 12, week 24 and week 48 (PBMCs)
2. Evolution of VZV-specific antibody over the study period, measured at baseline (first vaccine dose), week 4, week 8, week 12, week 24 and week 48 (plasma)
3. Occurrence of adverse events of Grade 2 or higher severity (from Electronic Data Capture [EDC]) between screening and week 48
4. Viral sequence of shingles infections (in swabs) measured using nucleic acid magnetic bead extraction and real-time RT-PCR (reverse transcription and polymerase chain reaction) to determine the presence of viral genes, viral titres and viral sequence at week 48

Overall study start date

15/09/2023

Overall study end date

31/05/2025

Reason abandoned (if study stopped)

Participant inclusion criteria

1. Able and willing to comply with the requirements of the protocol
2. Able and willing to provide fully informed consent
3. Male or non-pregnant, non-lactating females
4. People living with HIV >50 years and over OR have perinatally acquired HIV (any CD4) and are aged 18 years and over
5. If female, of child-bearing age, not sterilised and participating in sexual intercourse that could result in pregnancy, using at least one acceptable method of contraception when engaging in sexual activities that can result in pregnancy, beginning at screening through month 4. Acceptable methods of contraception include the following:
5.1. Hormonal contraception
5.2. Male or female condom
5.3. Diaphragm or cervical cap with a spermicide
5.4. Intrauterine device

Participant type(s)

Patient

Age group

Adult

Lower age limit

18 Years

Sex

Both

Target number of participants

70

Participant exclusion criteria

1. Active herpes zoster disease in past 6 months preceding the first dose of study vaccine
2. If female, planning to get pregnant, currently pregnant (evidence from positive serum or urine pregnancy test), or breastfeeding
3. Used any investigational or non-registered product other than the study vaccine within 30 days preceding the first dose of study vaccine or planned use during the study period
4. Vaccinated within the 12 months preceding the first dose of study vaccine or planned to be vaccinated during the study with a (non-study) vaccine against herpes zoster or varicella zoster virus
5. History of any reaction or hypersensitivity likely to be exacerbated by any vaccine component
6. Received or planned to receive a live vaccine in the period starting 30 days before the first dose of study vaccine and ending 30 days after the last dose of study vaccine or had received or planned to receive a non-replicating vaccine within 8 days before or within 14 days after either dose of study vaccine
7. Acute disease and/or fever at the time of enrolment. Fever is defined as temperature ≥ 37.5°C (99.5°F) on oral, axillary or tympanic setting. The preferred route for recording temperature in this study will be oral. Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may, be enrolled at the discretion of the investigator.
8. Chronic administration (defined as more than 15 consecutive days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. For corticosteroids, this will mean prednisone < 20 mg/day, or equivalent, is allowed. Inhaled and topical steroids are allowed. Drugs include: chemotherapeutic drugs, immunomodulators and systemic immunosuppressive treatments, oral glucocorticoids >20 mg/day, cyclosporine, methotrexate, interleukins and/or cytokines, immunotherapies (including TNF blockers).
9. Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the subject due to participation in the study
10. History of potential immune-mediated disease (pIMD). Note: If the subject has any condition on the list of pIMDs specified in the protocol, they must be excluded unless the aetiology is clearly documented to be non-immune mediated

Recruitment start date

18/03/2024

Recruitment end date

01/08/2024

Countries of recruitment

England, United Kingdom

Study participating centre

Guys Hospital
Guys Hospital
Great Maze Pond
London
SE1 9RT
United Kingdom

Study participating centre

St Mary's Hospital
Praed St
London
W2 1NY
United Kingdom

Study participating centre

Churchill Hospital
Churchill Hospital
Old Road
Headington
Oxford
OX3 7LE
United Kingdom

Organisation

Guy's and St Thomas' NHS Foundation Trust

Sponsor details

Department of Genitourinary Medicine
Guys Hospital
Great Maze Pond
London
SE1 9RT
England
United Kingdom
+44 (0)7703469925
amy.holton@kcl.ac.uk

Sponsor type

Hospital/treatment centre

Website

http://www.guysandstthomas.nhs.uk/Home.aspx

ROR

https://ror.org/00j161312

Funder type

Industry

Funder name

GlaxoSmithKline

Alternative name(s)

GlaxoSmithKline plc., GSK plc., GSK

Funding Body Type

government organisation

Funding Body Subtype

For-profit companies (industry)

Location

United Kingdom

Publication and dissemination plan

1. Peer-reviewed scientific journals
2. Conference presentation
3. Submission to regulatory authorities
4. Chief Investigator contact details will be available on a public database, together with the trial results
5. Requests for access to anonymised datasets will be considered by the Chief Investigator on a case-by-case basis.

Intention to publish date

31/05/2026

Individual participant data (IPD) sharing plan

The data-sharing plans for the current study are unknown and will be made available at a later date

IPD sharing plan summary

Data sharing statement to be made available at a later date

Study outputs

• ISRCTN34192276 SAGE Protocol V1.1 23Oct2023.pdf