Inflammatory Bowel DiseasesPhase 2/3NCT04083157
Intra-dermal With Topical Imiquimod Pretreatment Versus Intra-muscular Hepatitis B Vaccination in IBD Patients
A Phase 2/3 study testing Intradermal hepatitis B vaccine with imiquimod and Intramuscular hepatitis B vaccine with aqueous cream in people with Inflammatory Bowel Diseases and Hepatitis B, run by The University of Hong Kong at 1 site in China.
Trial summary
Inflammatory bowel disease (IBD) has witnessed a rising incidence globally and in Hong Kong, an area where chronic hepatitis B (CHB) remains endemic. IBD patients are usually immunocompromised due to the disease itself and secondary to the use of medications including immunosuppressants and biologics, predisposing… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Inflammatory Bowel Diseases, Hepatitis B
- What is being tested?
- Intradermal hepatitis B vaccine with imiquimod and Intramuscular hepatitis B vaccine with aqueous cream
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 104 participants
- Where
- 1 siteChina
- Study dates
- 12 Aug 2019to 30 Dec 2021
- 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
- Adults aged over 18 years old
- Confirmed IBD diagnosis (Ulcerative colitis, Crohns disease or IBD-Unclassified)
- HBsAg -ve / anti-HBs / antiHBc -ve
- Subjects must give written informed consent
- Subjects must be available to complete the study and comply with study procedures
Who cannot join
- Inability or unwilling to follow all required study procedures
- History of allergy or severe adverse reaction to the study vaccines, their components, topical imiquimod or aqueous cream
- Pregnant or lactating women
- HBsAg / anti-HBs / anti-HBc +ve
- Confirmed hepatitis C virus (HCV) (anti-HCV +ve) infection
- Fever (axillary temperature ≥ 38°C or oral temperature ≥ 38.5°C within 3 days of intended study vaccination, subjects can be recruited after the febrile episode subsides
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- Have an active neoplastic disease
- Have any condition which the investigator believes may prevent successful completion of the study or interfere with results of the study
- Received an experimental agent (vaccine, drug, biologic, medication) within 1 month prior to vaccination or expect to receive an experimental agent during the study period
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Intra-dermal With Topical Imiquimod Pretreatment Versus Intra-muscular Hepatitis B Vaccination in IBD Patients - a Double-blind Randomized Controlled Trial
Inflammatory bowel disease (IBD) has witnessed a rising incidence globally and in Hong Kong, an area where chronic hepatitis B (CHB) remains endemic. IBD patients are usually immunocompromised due to the disease itself and secondary to the use of medications including immunosuppressants and biologics, predisposing them to various opportunistic infection including hepatitis. Vaccination against hepatitis B virus (HBV) is recommended to prevent CHB and its related complications including flare up of acute hepatitis, cirrhosis and hepatocellular carcinoma. However, it is reported that efficacy with conventional intramuscular hepatitis B vaccination in IBD patients is suboptimal, especially among those receiving biologic therapies. Various strategies in boosting vaccine immunogenicity including the utilization of higher vaccination dose, shorter dosing interval, or alternate route of vaccine administration have been studied.6
Intradermal route of vaccination has been recently shown to be an effective way in augmenting immune response in specific patient groups who are known poor responders, including elderly and immunocompromised patients. In addition, topical imiquimod, a synthetic agonist of toll-like receptor 7 (TLR7), has been shown to further boost up the immunogenicity response when applied to the site before intradermal vaccination. The proposed study is the first clinical trial comparing the efficacy of intradermal hepatitis B vaccination with adjuvant topical application of imiquimod cream with the conventional intramuscular hepatitis B vaccination in IBD patients.
Read the detailed description
Aim of study To compare the efficacy of intradermal hepatitis B vaccination with adjuvant topical imiquimod with conventional intramuscular hepatitis B vaccination in IBD patients.
Methodology Patient recruitment IBD patients newly referred to or currently followed up at Department of Medicine, Queen Mary Hospital will be screened for CHB status (HBsAg/Anti-HBs/Anti-HBc). Patients without CHB infection and evidence of prior HBV vaccination i.e. HBsAg -ve /Anti-HBc-ve/ Anti-HBs -ve will be recruited into the study. Eligible patients will be randomized to receive either intradermal vaccination with Engerix B with topical imiquimod or intramuscular vaccination with Engerix-B with topical aqueous cream as the control arm.
Randomization Eligible patients will be randomized in 1:1 ratio to receive intradermal hepatitis B vaccination (Engerix B) with topical imiquimod cream (as the study arm) or intramuscular hepatitis B vaccination (Engerix-B) with topical aqueous cream (as the control arm). Computer generated random number is used for randomization. Randomization sequences will be kept in opaque envelope and kept by a research staff not directly involved in this study. Once the patient has consented to the study, that research staff will open the envelope and notified the study nurse only of the vaccine allocation. In case of medical emergency or severe adverse reaction to the study medication, unblinding can be performed after notification of the principal investigator who will break the randomization code by revealing the randomization sequence assigned to the concerned study subject.
Vaccine administration Vaccination schedule is identical between the two arms with 3 doses given at 0, 1, 6 month. Participants in the study arm will receive 20 mcg intradermal Engerix-B at two separate sites (10 mcg/0.5 ml) with topical imiquimod ointment pre-treatment 5 minutes before injection. Participants in the control arm will receive 20 mcg intramuscular Engerix-B at two separate sites (10 mcg/ 0.5 ml) with topical placebo aqueous cream pretreatment 5 minutes before injection. The topical treatment will be given in a 4x4cm2 marked at the deltoid on each arm. Vaccination will be administered at clinic by dedicated study nurse, who is not involved in subsequent management of the participants. Both the investigators and the participants will be blinded to the result of randomization as only the study nurse know the route of administration.
Follow up Follow up visits will be arranged at 1,6,12 month after first dose of vaccine. Blood will be taken during each follow up visits for anti-HBs titres.
- Conditions
- Inflammatory Bowel Diseases, Hepatitis B
- Being tested
- Intradermal hepatitis B vaccine with imiquimod, Intramuscular hepatitis B vaccine with aqueous cream
- Medical subject headings
- Inflammatory Bowel Diseases, Hepatitis B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intradermal hepatitis B vaccine with imiquimodBiological
Intradermal hepatitis B vaccine with topical imiquimod pretreatment
Intramuscular hepatitis B vaccine with aqueous creamBiological
Intramuscular hepatitis B vaccine with topical aqueous cream pretreatment
| Study group | Role | What they receive |
|---|---|---|
| Intradermal hepatitis B vaccine with imiquimod | Experimental | Subjects in the study arm will receive 20 mcg intradermal Engerix-B at two separate sites (10 mcg/0.5 ml) with topical imiquimod ointment pre-treatment 5 minutes before injection. Receives: Biological: Intradermal hepatitis B vaccine with imiquimod |
| Intramuscular hepatitis B vaccine with aqueous cream | Active comparator | Subjects in the control arm will receive 20 mcg intramuscular Engerix-B at two separate sites (10 mcg/ 0.5 ml) with topical placebo aqueous cream pretreatment 5 minutes before injection. Receives: Biological: Intramuscular hepatitis B vaccine with aqueous cream |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sero-protection rate to HBV
Percentage of recruited subjects with anti-HBs titre ≥ 10 IU/L
Measured: 12 months after first dose of vaccine
Secondary outcomes (5)
Injection site adverse effect of intradermal hepatitis B vaccine in IBD patients
Injection site adverse effect recorded as following, with left and right arm recorded separately:
Pain - 0 = no pain / 1 = pain on touch / 2 = pain during arm raising / 3 = pain on arm movement Presence or absence of the following Itching Swelling Hot sensation Bruise
Measured: up to 7 days after each dose of vaccination
Systemic adverse effect of intradermal hepatitis B vaccine in IBD patients
Presence of absence of systemic adverse effect recorded as following:
Fever Malaise Headache Myalgia Arthralgia Nausea Diarrhoea
Measured: up to 7 days after each dose of vaccination
Sero-protection rate to HBV at 1 and 6 months after dose of vaccine
Measured: 1 and 6 month after first dose of vaccine
Percentage of good responder defined as anti-HBs ≥ 100 IU/L
Measured: 12 month after first dose of vaccine
Geometric mean concentration of anti-HBs at 1, 6 and 12 months after first dose of vaccine
Measured: 1, 6 and 12 month after first dose of vaccine
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2019
- Study start12 Aug 2019
- Primary completion30 Dec 2020
- Study completion30 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Inflammatory Bowel DiseasesStudies of the same condition, open and under way.
- More trials run by The University of Hong KongThe sponsor's other registered studies.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 104 participants (actual)
Sponsor and investigators
- Lead sponsor
- The University of Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Wai Keung Leung, MD, Study director, The University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04083157
- Sponsor's protocol ID
- IBDHepBVaccine
- Status last verified
- May 2022
- First submitted
- 2 Sep 2019
- Last updated
- 18 May 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Ko KL, Lam YF, Cheung KS, Hung IF, Leung WK. Clinical trial: intra dermal hepatitis B vaccination with topical imiquimod versus intra muscular hepatitis B vaccination in patients with inflammatory bowel disease. Aliment Pharmacol Ther. 2022 Jul;56(2):301-309. doi: 10.1111/apt.16970. Epub 2022 May 11.
PubMed 35546255
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intra-dermal With Topical Imiquimod Pretreatment Versus Intra-muscular Hepatitis B Vaccination in IBD Patients - a Double-blind Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT04083157
- Acronym / sponsor ID
- IBDHepBVaccine
- Conditions
- Inflammatory Bowel Diseases, Hepatitis B
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 104 participants (actual)
- Lead sponsor
- The University of Hong KongUniversity, hospital or other
- Study start
- 12 Aug 2019 (actual)
- Primary completion
- 30 Dec 2020 (actual)
- Study completion
- 30 Dec 2021 (actual)
- First posted
- 10 Sep 2019 (actual)
- 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.
Inflammatory bowel disease (IBD) has witnessed a rising incidence globally and in Hong Kong, an area where chronic hepatitis B (CHB) remains endemic. IBD patients are usually immunocompromised due to the disease itself and secondary to the use of medications including immunosuppressants and biologics, predisposing them to various opportunistic infection including hepatitis. Vaccination against hepatitis B virus (HBV) is recommended to prevent CHB and its related complications including flare up of acute hepatitis, cirrhosis and hepatocellular carcinoma. However, it is reported that efficacy with conventional intramuscular hepatitis B vaccination in IBD patients is suboptimal, especially among those receiving biologic therapies. Various strategies in boosting vaccine immunogenicity including the utilization of higher vaccination dose, shorter dosing interval, or alternate route of vaccine administration have been studied.6
Intradermal route of vaccination has been recently shown to be an effective way in augmenting immune response in specific patient groups who are known poor responders, including elderly and immunocompromised patients. In addition, topical imiquimod, a synthetic agonist of toll-like receptor 7 (TLR7), has been shown to further boost up the immunogenicity response when applied to the site before intradermal vaccination. The proposed study is the first clinical trial comparing the efficacy of intradermal hepatitis B vaccination with adjuvant topical application of imiquimod cream with the conventional intramuscular hepatitis B vaccination in IBD patients.
Detailed description
Aim of study To compare the efficacy of intradermal hepatitis B vaccination with adjuvant topical imiquimod with conventional intramuscular hepatitis B vaccination in IBD patients.
Methodology Patient recruitment IBD patients newly referred to or currently followed up at Department of Medicine, Queen Mary Hospital will be screened for CHB status (HBsAg/Anti-HBs/Anti-HBc). Patients without CHB infection and evidence of prior HBV vaccination i.e. HBsAg -ve /Anti-HBc-ve/ Anti-HBs -ve will be recruited into the study. Eligible patients will be randomized to receive either intradermal vaccination with Engerix B with topical imiquimod or intramuscular vaccination with Engerix-B with topical aqueous cream as the control arm.
Randomization Eligible patients will be randomized in 1:1 ratio to receive intradermal hepatitis B vaccination (Engerix B) with topical imiquimod cream (as the study arm) or intramuscular hepatitis B vaccination (Engerix-B) with topical aqueous cream (as the control arm). Computer generated random number is used for randomization. Randomization sequences will be kept in opaque envelope and kept by a research staff not directly involved in this study. Once the patient has consented to the study, that research staff will open the envelope and notified the study nurse only of the vaccine allocation. In case of medical emergency or severe adverse reaction to the study medication, unblinding can be performed after notification of the principal investigator who will break the randomization code by revealing the randomization sequence assigned to the concerned study subject.
Vaccine administration Vaccination schedule is identical between the two arms with 3 doses given at 0, 1, 6 month. Participants in the study arm will receive 20 mcg intradermal Engerix-B at two separate sites (10 mcg/0.5 ml) with topical imiquimod ointment pre-treatment 5 minutes before injection. Participants in the control arm will receive 20 mcg intramuscular Engerix-B at two separate sites (10 mcg/ 0.5 ml) with topical placebo aqueous cream pretreatment 5 minutes before injection. The topical treatment will be given in a 4x4cm2 marked at the deltoid on each arm. Vaccination will be administered at clinic by dedicated study nurse, who is not involved in subsequent management of the participants. Both the investigators and the participants will be blinded to the result of randomization as only the study nurse know the route of administration.
Follow up Follow up visits will be arranged at 1,6,12 month after first dose of vaccine. Blood will be taken during each follow up visits for anti-HBs titres.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intradermal hepatitis B vaccine with imiquimod | Experimental | Biological: Intradermal hepatitis B vaccine with imiquimodSubjects in the study arm will receive 20 mcg intradermal Engerix-B at two separate sites (10 mcg/0.5 ml) with topical imiquimod ointment pre-treatment 5 minutes before injection. |
| Intramuscular hepatitis B vaccine with aqueous cream | Active comparator | Biological: Intramuscular hepatitis B vaccine with aqueous creamSubjects in the control arm will receive 20 mcg intramuscular Engerix-B at two separate sites (10 mcg/ 0.5 ml) with topical placebo aqueous cream pretreatment 5 minutes before injection. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Adults aged over 18 years old
- Confirmed IBD diagnosis (Ulcerative colitis, Crohns disease or IBD-Unclassified)
- HBsAg -ve / anti-HBs / antiHBc -ve
- Subjects must give written informed consent
- Subjects must be available to complete the study and comply with study procedures
Key exclusion criteria (9 listed)
- Inability or unwilling to follow all required study procedures
- History of allergy or severe adverse reaction to the study vaccines, their components, topical imiquimod or aqueous cream
- Pregnant or lactating women
- HBsAg / anti-HBs / anti-HBc +ve
- Confirmed hepatitis C virus (HCV) (anti-HCV +ve) infection
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 |
|---|---|---|
| Intradermal hepatitis B vaccine with imiquimodIntradermal hepatitis B vaccine with topical imiquimod pretreatment | Biological | Intradermal hepatitis B vaccine with imiquimod |
| Intramuscular hepatitis B vaccine with aqueous creamIntramuscular hepatitis B vaccine with topical aqueous cream pretreatment | Biological | Intramuscular hepatitis B vaccine with aqueous cream |
Primary outcome
Sero-protection rate to HBV
Time frame: 12 months after first dose of vaccine
Percentage of recruited subjects with anti-HBs titre ≥ 10 IU/L
5 secondary outcomes
Injection site adverse effect of intradermal hepatitis B vaccine in IBD patients
Time frame: up to 7 days after each dose of vaccination
Systemic adverse effect of intradermal hepatitis B vaccine in IBD patients
Time frame: up to 7 days after each dose of vaccination
Sero-protection rate to HBV at 1 and 6 months after dose of vaccine
Time frame: 1 and 6 month after first dose of vaccine
Percentage of good responder defined as anti-HBs ≥ 100 IU/L
Time frame: 12 month after first dose of vaccine
Geometric mean concentration of anti-HBs at 1, 6 and 12 months after first dose of vaccine
Time frame: 1, 6 and 12 month after first dose of vaccine
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 18 May 2022.
- Derived from this study: PubMed 35546255Ko KL, Lam YF, Cheung KS, Hung IF, Leung WK. Clinical trial: intra dermal hepatitis B vaccination with topical imiquimod versus intra muscular hepatitis B vaccination in patients with inflammatory bowel disease. Aliment Pharmacol Ther. 2022 Jul;56(2):301-309. doi: 10.1111/apt.16970. Epub 2022 May 11.
- Individual participant dataSharing planned: Undecided
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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.
Wai Keung Leung, MD study director
The University of Hong Kong
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 Intradermal hepatitis B vaccine with imiquimod and Intramuscular hepatitis B vaccine with aqueous cream in people with Inflammatory Bowel Diseases and Hepatitis B, run by The University of Hong Kong at 1 site in China.
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 5 inclusion and 9 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 18 May 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 China. 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?
Sero-protection rate to HBV (time frame: 12 months after first dose of vaccine). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04083157, which also lists 1 linked publication.
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 18 May 2022.