HIVPhase 2/3NCT02434848
A Pilot Study Comparing the Immunogenicity of Fendrix vs. Double-dose Engerix B in HIV-infected Non-responders to Standard Hepatitis B Vaccination Courses
A Phase 2/3 study testing Engerix B and Fendrix in people with HIV and Communicable Diseases, run by Sheffield Teaching Hospitals NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
Hepatitis B virus (HBV) infection can result in a greater risk of adverse outcomes in HIV-infected individuals, including more rapid progression to cirrhosis and associated complications such as hepatocellular carcinoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV, Communicable Diseases, Hepatitis B
- What is being tested?
- Engerix B and Fendrix
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 23 Jul 2015to 10 Jun 2022
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18
- HIV-1 infected
- On antiretroviral therapy
- Viral load undetectable (for at least 6 months, last available measurement within 3 months)
- History of having received at least one complete course of non-Fendrix-based hepatitis B vaccination in the past. Patients who have already received a double-dose Engerix B course in the past will still be eligible.
- HBsAb levels persistently <10IU/L despite vaccination
Who cannot join
- A history of hypersensitivity to any previous hepatitis B vaccination
- A history of hypersensitivity to any components of either Engerix B or Fendrix (see Summary of Product Characteristics).
- Currently undergoing an incomplete course of any hepatitis B vaccination
- Having received at least one vaccination with Fendrix in the past
- Recipient of any other vaccination within the last 2 weeks
- Any previously detectable HBsAb level (≥10)
Show all 12Show fewer
- Pregnant or breastfeeding
- Individuals who have a current severe febrile illness
- Individuals with a known and current history of anaemia or any symptoms (shortness of breath, chronic fatigue, chest pain or pallor) suggestive of possible anaemia or haemoglobin below the lower limit of sex adjusted normal range on a full blood count taken within the last 3 months.
- Current (active) participation in any clinical trial
- Inability to communicate in English or convey willingness to participate
- End Stage Renal Disease undergoing renal replacement therapy
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust
Sheffield, South Yorkshire, S10 2JF
About this study
Hepatitis B virus (HBV) infection can result in a greater risk of adverse outcomes in HIV-infected individuals, including more rapid progression to cirrhosis and associated complications such as hepatocellular carcinoma. For this reason, as well as the shared routes of transmission between the two viruses, UK and International guidance recommends that all HBV-negative HIV-infected individuals be offered vaccination against HBV. Unfortunately, response rates in this population can be as low as 17.5 - 40% to standard vaccination courses. To improve this response, strategies such as the use of double dose of standard vaccines (e.g. Engerix B) is recommended in several guidelines for previous non-responders, although there is currently limited evidence for this approach. An alternative strategy is to use vaccines with novel adjuvants such as Fendrix and observational clinical data in the Investigators HIV cohort suggests that response rates can be as high as 81% of individuals achieving HBV surface antibody (HBsAb) levels >100 in a group that did not respond to previous standard HBV vaccine courses. However, the cost of Fendrix is considerably higher than Engerix B and controlled trials are required to confirm whether this approach is warranted. Furthermore, insights into the potential mechanisms by which Fendrix may elicit better responses would be valuable in optimising future vaccine strategies in this population.
The Investigators propose to conduct a randomised, open label, active-controlled pilot study comparing double dose Engerix B and Fendrix in HIV-infected non-responders to standard HBV vaccine courses, which will provide the necessary data to design and power a larger multicentre randomised controlled trial. Outcome measures will include the proportion of individuals seroconverting with HBsAb levels >100 following each vaccination course, the magnitude and quality of the HBV-specific CD4+ T-cell responses elicited by each vaccine and the durability of the HBsAb response at 1 year following the end of vaccination.
Read the detailed description
To compare the immunological responses in HIV-infected non-responders to standard hepatitis B vaccination courses to immunization with either double-dose Engerix B or Fendrix:
- Investigators will measure the proportion of individuals seroconverting with Hepatitis B surface antibody titres of >100 (and ≥10) IU/ml at 8 weeks after the immunisation course, as well as the durability of this response at 1 year following the completion of the course. The primary aim will be to provide some preliminary data from a head to head study of these two approaches with which to power a larger multi-centre randomized controlled trial.
- Investigators will define the magnitude and quality of the Hepatitis B-specific CD4+ T-cell response following vaccination, thus obtaining key immunological data to fill the knowledge gap in T-cell responses to Hepatitis B vaccination, required to support the rationale design of future multi-centre, randomized study comparing vaccination strategies in HIV-infected non-responders to standard Hepatitis B vaccine courses.
The research is original. There is only one published study to date looking at the efficacy of double-dose Engerix B in HIV-infected non-responders to standard courses1. There is currently anecdotal experience of the use of Fendrix in this group from the Investigators cohort and others. There are no head-to-head comparisons of these two strategies.
- Conditions
- HIV, Communicable Diseases, Hepatitis B, HBV, Infectious Diseases
- Being tested
- Engerix B, Fendrix
- Medical subject headings
- Communicable Diseases, Hepatitis B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Engerix BDrug
Engerix B 20 micrograms/1ml Licensee: GlaxoSmithKline UK Intra-muscular
Prescription and administration:
The vaccine will be stored in the Investigators pharmacy as clinical trial stock and dispensed on a subject by subject basis.
Shelf life and storage The product must be kept refrigerated (2°C - 8°C). Prescriptions will be written and dispensed from pharmacy on the day of consent, screening and vaccination. The shelf life is 3 years.
FendrixDrug
Fendrix suspension for injection GlaxoSmithKline UK
Route of Administration, dose regimen:
Intra-muscular Dose: 0.5ml (20mcg of Hepatitis B Surface Antigen) per vaccination at baseline and weeks 4, 8 and 24.
Prescription and administration:
The vaccine will be stored in the Investigators pharmacy as clinical trial stock and dispensed on a subject by subject basis.
Packaging and labeling The vaccine will have clinical trial labeling. Shelf-life and storage The product must be kept refrigerated (2°C - 8°C).
The shelf life is 3 years.
| Study group | Role | What they receive |
|---|---|---|
| Engerix B | Active comparator | 15 subjects per group (n = 30 in total) Receives: Drug: Engerix B |
| Fendrix | Active comparator | 15 subjects per group (n = 30 in total) Receives: Drug: Fendrix |
What is being measured
The primary outcome is the main question the study is designed to answer.
The proportion of individuals seroconverting with Hepatitis B surface antibody titres of >100 (and ≥10) IU/ml
Measured: 8 weeks
Secondary outcomes (2)
Hepatitis B-specific CD4+ T-cell response at 2 weeks following the first vaccination and 2 weeks following the 3rd vaccination.
Measured: 2 weeks following the first vaccination and 2 weeks following the 3rd vaccination.
The proportion of individuals seroconverting with Hepatitis B surface antibody titres of >100 (and ≥10) IU/ml
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 May 2015 (estimated)
- Study start23 Jul 2015
- Primary completion10 Jun 2022
- Study completion10 Jun 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIVStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sheffield Teaching Hospitals NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02434848
- Sponsor's protocol ID
- STH17302
- Status last verified
- Sep 2022
- First submitted
- 30 Apr 2015
- Last updated
- 29 Sep 2022
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study Comparing the Immunogenicity of Fendrix vs. Double-dose Engerix B in HIV-infected Non-responders to Standard Hepatitis B Vaccination Courses
- ClinicalTrials.gov ID
- NCT02434848
- Acronym / sponsor ID
- STH17302
- Conditions
- HIV, Communicable Diseases, Hepatitis B, HBV, Infectious Diseases
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Sheffield Teaching Hospitals NHS Foundation TrustUniversity, hospital or other
- Study start
- 23 Jul 2015 (actual)
- Primary completion
- 10 Jun 2022 (actual)
- Study completion
- 10 Jun 2022 (actual)
- First posted
- 5 May 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Hepatitis B virus (HBV) infection can result in a greater risk of adverse outcomes in HIV-infected individuals, including more rapid progression to cirrhosis and associated complications such as hepatocellular carcinoma. For this reason, as well as the shared routes of transmission between the two viruses, UK and International guidance recommends that all HBV-negative HIV-infected individuals be offered vaccination against HBV. Unfortunately, response rates in this population can be as low as 17.5 - 40% to standard vaccination courses. To improve this response, strategies such as the use of double dose of standard vaccines (e.g. Engerix B) is recommended in several guidelines for previous non-responders, although there is currently limited evidence for this approach. An alternative strategy is to use vaccines with novel adjuvants such as Fendrix and observational clinical data in the Investigators HIV cohort suggests that response rates can be as high as 81% of individuals achieving HBV surface antibody (HBsAb) levels >100 in a group that did not respond to previous standard HBV vaccine courses. However, the cost of Fendrix is considerably higher than Engerix B and controlled trials are required to confirm whether this approach is warranted. Furthermore, insights into the potential mechanisms by which Fendrix may elicit better responses would be valuable in optimising future vaccine strategies in this population.
The Investigators propose to conduct a randomised, open label, active-controlled pilot study comparing double dose Engerix B and Fendrix in HIV-infected non-responders to standard HBV vaccine courses, which will provide the necessary data to design and power a larger multicentre randomised controlled trial. Outcome measures will include the proportion of individuals seroconverting with HBsAb levels >100 following each vaccination course, the magnitude and quality of the HBV-specific CD4+ T-cell responses elicited by each vaccine and the durability of the HBsAb response at 1 year following the end of vaccination.
Detailed description
To compare the immunological responses in HIV-infected non-responders to standard hepatitis B vaccination courses to immunization with either double-dose Engerix B or Fendrix:
- Investigators will measure the proportion of individuals seroconverting with Hepatitis B surface antibody titres of >100 (and ≥10) IU/ml at 8 weeks after the immunisation course, as well as the durability of this response at 1 year following the completion of the course. The primary aim will be to provide some preliminary data from a head to head study of these two approaches with which to power a larger multi-centre randomized controlled trial.
- Investigators will define the magnitude and quality of the Hepatitis B-specific CD4+ T-cell response following vaccination, thus obtaining key immunological data to fill the knowledge gap in T-cell responses to Hepatitis B vaccination, required to support the rationale design of future multi-centre, randomized study comparing vaccination strategies in HIV-infected non-responders to standard Hepatitis B vaccine courses.
The research is original. There is only one published study to date looking at the efficacy of double-dose Engerix B in HIV-infected non-responders to standard courses1. There is currently anecdotal experience of the use of Fendrix in this group from the Investigators cohort and others. There are no head-to-head comparisons of these two strategies.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Engerix B | Active comparator | Drug: Engerix B15 subjects per group (n = 30 in total) |
| Fendrix | Active comparator | Drug: Fendrix15 subjects per group (n = 30 in total) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age ≥18
- HIV-1 infected
- On antiretroviral therapy
- Viral load undetectable (for at least 6 months, last available measurement within 3 months)
- History of having received at least one complete course of non-Fendrix-based hepatitis B vaccination in the past. Patients who have already received a double-dose Engerix B course in the past will still be eligible.
Key exclusion criteria (12 listed)
- A history of hypersensitivity to any previous hepatitis B vaccination
- A history of hypersensitivity to any components of either Engerix B or Fendrix (see Summary of Product Characteristics).
- Currently undergoing an incomplete course of any hepatitis B vaccination
- Having received at least one vaccination with Fendrix in the past
- Recipient of any other vaccination within the last 2 weeks
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Engerix BEngerix B 20 micrograms/1ml Licensee: GlaxoSmithKline UK Intra-muscular Prescription and administration: The vaccine will be stored in the Investigators pharmacy as clinical trial stock and dispensed on a subject by subject basis. Shelf life and storage The product must be kept refrigerated (2°C - 8°C). Prescriptions will be written and dispensed from pharmacy on the day of consent, screening and vaccination. The shelf life is 3 years. | Drug | Engerix B |
| FendrixFendrix suspension for injection GlaxoSmithKline UK Route of Administration, dose regimen: Intra-muscular Dose: 0.5ml (20mcg of Hepatitis B Surface Antigen) per vaccination at baseline and weeks 4, 8 and 24. Prescription and administration: The vaccine will be stored in the Investigators pharmacy as clinical trial stock and dispensed on a subject by subject basis. Packaging and labeling The vaccine will have clinical trial labeling. Shelf-life and storage The product must be kept refrigerated (2°C - 8°C). The shelf life is 3 years. | Drug | Fendrix |
Primary outcome
The proportion of individuals seroconverting with Hepatitis B surface antibody titres of >100 (and ≥10) IU/ml
Time frame: 8 weeks
2 secondary outcomes
Hepatitis B-specific CD4+ T-cell response at 2 weeks following the first vaccination and 2 weeks following the 3rd vaccination.
Time frame: 2 weeks following the first vaccination and 2 weeks following the 3rd vaccination.
The proportion of individuals seroconverting with Hepatitis B surface antibody titres of >100 (and ≥10) IU/ml
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Engerix B and Fendrix in people with HIV and Communicable Diseases, run by Sheffield Teaching Hospitals NHS Foundation Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The proportion of individuals seroconverting with Hepatitis B surface antibody titres of >100 (and ≥10) IU/ml (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2022.