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Evaluation of Intradermal Hepatitis B Vaccine After IMIQUIMOD's Application, in Cirrhotics Who Did Not Respond to the Usual Vaccine Regimen (IDMODVHB)

Primary Purpose

Cirrhosis, Liver, Vaccination Failure, HBV

Status

Not yet recruiting

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

IMIQUIMOD cream

HEPATITIS B SURFACE ANTIGEN

About this trial

This is an interventional prevention trial for Cirrhosis, Liver

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Adults (> 18 years old)
- Cirrhotic patient, all etiologies except related to chronic HBV infection.
- Cirrhotic patient who did not respond to a 1st conventional hepatitis B vaccination regimen administered intramuscularly (ac Anti HBs < 10 mUI/ml)
- Person affiliated to a social security plan
- Person who received complete information about the organization of the research and who signed informed consent

Exclusion Criteria:

Patients with contraindication to the use of an intramuscular vaccine : Patients on Anticoagulants; Hemophiliac Patients, Patients with Severe Hemostasis Disorder (objectified by TP < 30%; and/or a Thombopenia with platelets < 30G/L)
Patients with end-stage chronic kidney failure defined by DFG <15ml/min/1.73m2 _ Hemodialysised Patients
Patients with a skin condition that does not allow vaccination (intradermal or intra-muscle): Skin sores on both arms: ulcers/abrasions/bubbles ; without healthy skin intervals.
Femme of childbearing age who does not have an effective method of contraception for the duration of the study. Effective contraceptive methods are defined as combined hormonal contraception (containing estrogen and progestin) combined with ovulation inhibition (oral, intravaginal, transdermal); or progestin-only hormonal contraception combined with ovulation inhibition (oral, injectable, implantable); or intrauterine device (IUD); or intrauterine hormone delivery system (IUS); or bilateral tubal occlusion; or a vasectomized partner; or sexual abstinence; Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. Menopause is defined as the absence of menstruation for at least 12 months. According to CTFG recommendations related to contraception and pregnancy testing in clinical trials; version 1.1 of 21/09/2020.
Personne referred to sections L. 1121-5, L. 1121-7 and L1121-8 of the Public Health Code. Pregnant, parturient or breastfeeding mother Minor (unassecipated) An adult subject to a legal protection measure (tutelage, curate, safeguarding of justice) Adult person undying to express consent
Persons deprived of liberty by judicial or administrative decision, persons receiving psychiatric care under sections L. 3212-1 and L. 32131.
Vaccination during the 4 weeks (28 days) prior to the first vaccination in the trial
Previous vaccination with another investigational vaccine
Subjects who have received immunoglobulins, blood or blood derivatives within the last 3 months.
Known or suspected congenital or acquired immunodeficiency; immunosuppressive therapy within the last 6 months, such as cancer chemotherapy or radiotherapy; long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the last 3 months).
Acute respiratory infection or severe acute febrile illness (temperature ≥ 38.0°C), or a systemic reaction that may be of significant risk with vaccination in the month prior to inclusion.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Experimental

Arm Label

Intra-muscular vaccination (Group 1)

Intra-dermal vaccination group without application of IMIQUIMOD cream (Group 2)

Intra-dermal vaccination group with application of IMIQUIMOD cream (Group 3)

Arm Description

This group corresponds to the use of the vaccine as used in the current recommendations.

Administration mode change for Intra-dermal vaccination. ( Instead of Intra-musculaire ) , to have a comparative with the experimental group.

Intra-dermal vaccin administration, with an immunity booster few minutes before by IMIQUIMOD application cream. Experimental group.

Outcomes

Primary Outcome Measures

Proportion of patients in each groups, with HBs antibody levels greater than 10mUI/mL at 1 month of the last injection of vaccine

Describe the proportion of patients with HBs antibody levels greater than 10mUI/mL at 1 month of the last injection of vaccine ; with a M0M1-M6 vaccine regimen using 3 vaccines strategies: After simple intramuscular vaccine (IM) ( Control group , group 1) After simple intradermal vaccine without IMIQUIMOD ( Group 2 ) after IMIQUIMOD's application followed by intradermal vaccine administration ( Group 3 )

Secondary Outcome Measures

Describe the proportion of patients with an anti-HB antibody level greater than 10mUI/mL at 1 month of the first injection (M1) with a vaccine regimen according to the vaccine strategy

Rate of patients with an anti-HB antibody level greater than 10mUI/mL at 1 month of the first injection (M1) with a vaccine regimen according to the vaccine strategy

Describe the proportion of patients with an anti-HB antibody level greater than 10mUI/mL at 6 months of the first injection (M6) with a vaccine regimen according to the vaccine strategy

Rate of patients with an anti-HB antibody level greater than 10mUI/mL at 6 months of the first injection (M6) with a vaccine regimen according to the vaccine strategy

Describe the evolution of the level of anti-HBs antibodies between 2 successive visits according to the vaccine strategy

Anti-HBs Antibodies Level in the first vaccine injection = Day 0 / Month 0 Antibodies Level in the second vaccine injection = 30 days (1 month) after the first injection. Antibodies Level in the third vaccine injection = 180 days (6months) after the first vaccine injection (or 150 days/5months after the second vaccine injection) Antibodies Level at the end of the study : 210 days (7 months) after the first injection ; (or 30 days/1month after the third injection ) ;

Describe the rate of adverse events (by severity level) following the injection of a dose of intradermal vaccine

In each visit ( Month 1 , Month 6 , Month 7 ) we describe the rate of adverse events (by severity level) following the injection of a dose of intradermal vaccine

Describe the rate of adverse events (by severity level) following the injection of an intradermal vaccine dose after prior application of Imiquimod

In each visit ( Month 1 , Month 6 , Month 7 ) we describe the rate of adverse events (by severity level) after injection of an intradermal vaccine dose after prior application of Imiquimod

Full Information

NCT ID

NCT05028322

First Posted

July 6, 2021

Last Updated

August 27, 2021

Sponsor

Central Hospital, Nancy, France

1. Study Identification

Unique Protocol Identification Number

NCT05028322

Brief Title

Evaluation of Intradermal Hepatitis B Vaccine After IMIQUIMOD's Application, in Cirrhotics Who Did Not Respond to the Usual Vaccine Regimen

Acronym

IDMODVHB

Official Title

Effectiveness and Safety of Intra-Dermal Hepatitis B Vaccination After Topical Application of IMIQUIMOD, in Cirrhotics Patients, Who Did Not Respond to the Conventional Vaccine Regimen: a Pilot Study

Study Type

Interventional

2. Study Status

Record Verification Date

June 2021

Overall Recruitment Status

Not yet recruiting

Study Start Date

November 1, 2021 (Anticipated)

Primary Completion Date

December 1, 2024 (Anticipated)

Study Completion Date

December 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Central Hospital, Nancy, France

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

In a population of cirrhotics patients who did not responde to an anti-HBV vaccination according to the recommended vaccination, the goal is to : Describe the proportion of patients with HBs antibody levels greater than 10mUI/mL at 1 month of the last injection of vaccine ; with a M0-M1-M6 vaccine regimen using 3 vaccines strategies : After simple intramuscular vaccine (IM) ( Control group ) After simple intradermal vaccine after IMIQUIMOD's application followed by intradermal vaccine administration The main hypothesis of this study is : IMIQUIMOD acts as an immunity booster, so the combination of IMIQUIMOD with an intra-dermal injection of the anti-HBV vaccine allows better acquisition of post-vaccination immunization.

Detailed Description

This study will be in a population of Cirrhotic patients who have already received a HBV vaccination with a conventional regimen and who have not responded (characterized by a level of antibody Hbs < 10UI/ml at the end of the vaccine regimen). In current recommendations, up to 3 additional injections of HBV vaccine should be injected to obtain an antibody level> 10 mIU / ml. In this study, the investigator will describe the proportion of patients with HBs antibody levels greater than 10mUI/mL at 1 month of the last injection of vaccine ; with a M0-M1-M6 vaccine regimen using 3 vaccines strategies : After simple intramuscular vaccine (IM) ( Control group ) After simple intradermal vaccine after IMIQUIMOD's application followed by intradermal vaccine administration

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cirrhosis, Liver, Vaccination Failure, HBV, Vaccine Reaction

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Intra-muscular vaccination (Group 1)

Arm Type

Active Comparator

Arm Description

This group corresponds to the use of the vaccine as used in the current recommendations.

Arm Title

Intra-dermal vaccination group without application of IMIQUIMOD cream (Group 2)

Arm Type

Active Comparator

Arm Description

Administration mode change for Intra-dermal vaccination. ( Instead of Intra-musculaire ) , to have a comparative with the experimental group.

Arm Title

Intra-dermal vaccination group with application of IMIQUIMOD cream (Group 3)

Arm Type

Experimental

Arm Description

Intra-dermal vaccin administration, with an immunity booster few minutes before by IMIQUIMOD application cream. Experimental group.

Intervention Type

Drug

Intervention Name(s)

IMIQUIMOD cream

Intervention Description

Cream to apply before intra-dermal vaccine injection

Intervention Type

Biological

Intervention Name(s)

HEPATITIS B SURFACE ANTIGEN

Intervention Description

HBV Vaccine

Primary Outcome Measure Information:

Title

Proportion of patients in each groups, with HBs antibody levels greater than 10mUI/mL at 1 month of the last injection of vaccine

Description

Time Frame

1 month of the last injection of vaccine, it means 1 month after the end of the total procedure.

Secondary Outcome Measure Information:

Title

Describe the proportion of patients with an anti-HB antibody level greater than 10mUI/mL at 1 month of the first injection (M1) with a vaccine regimen according to the vaccine strategy

Description

Rate of patients with an anti-HB antibody level greater than 10mUI/mL at 1 month of the first injection (M1) with a vaccine regimen according to the vaccine strategy

Time Frame

1 month of the first vaccine injection (Month 1)

Title

Describe the proportion of patients with an anti-HB antibody level greater than 10mUI/mL at 6 months of the first injection (M6) with a vaccine regimen according to the vaccine strategy

Description

Rate of patients with an anti-HB antibody level greater than 10mUI/mL at 6 months of the first injection (M6) with a vaccine regimen according to the vaccine strategy

Time Frame

6 months of the first vaccine injection (Month 6)

Title

Describe the evolution of the level of anti-HBs antibodies between 2 successive visits according to the vaccine strategy

Description

Time Frame

-Day 0 / Month 0 ; - Day 30 / Month 1 ; - Day 180 / Month 6 ; - Day 210 / Month 7

Title

Describe the rate of adverse events (by severity level) following the injection of a dose of intradermal vaccine

Description

In each visit ( Month 1 , Month 6 , Month 7 ) we describe the rate of adverse events (by severity level) following the injection of a dose of intradermal vaccine

Time Frame

In each visit ( Month 1 , Month 6 , Month 7 )

Title

Describe the rate of adverse events (by severity level) following the injection of an intradermal vaccine dose after prior application of Imiquimod

Description

In each visit ( Month 1 , Month 6 , Month 7 ) we describe the rate of adverse events (by severity level) after injection of an intradermal vaccine dose after prior application of Imiquimod

Time Frame

In each visit ( Month 1 , Month 6 , Month 7 )

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Adults (> 18 years old) Cirrhotic patient, all etiologies except related to chronic HBV infection. Cirrhotic patient who did not respond to a 1st conventional hepatitis B vaccination regimen administered intramuscularly (ac Anti HBs < 10 mUI/ml) Person affiliated to a social security plan Person who received complete information about the organization of the research and who signed informed consent Exclusion Criteria: Patients with contraindication to the use of an intramuscular vaccine : Patients on Anticoagulants; Hemophiliac Patients, Patients with Severe Hemostasis Disorder (objectified by TP < 30%; and/or a Thombopenia with platelets < 30G/L) Patients with end-stage chronic kidney failure defined by DFG <15ml/min/1.73m2 _ Hemodialysised Patients Patients with a skin condition that does not allow vaccination (intradermal or intra-muscle): Skin sores on both arms: ulcers/abrasions/bubbles ; without healthy skin intervals. Femme of childbearing age who does not have an effective method of contraception for the duration of the study. Effective contraceptive methods are defined as combined hormonal contraception (containing estrogen and progestin) combined with ovulation inhibition (oral, intravaginal, transdermal); or progestin-only hormonal contraception combined with ovulation inhibition (oral, injectable, implantable); or intrauterine device (IUD); or intrauterine hormone delivery system (IUS); or bilateral tubal occlusion; or a vasectomized partner; or sexual abstinence; Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. Menopause is defined as the absence of menstruation for at least 12 months. According to CTFG recommendations related to contraception and pregnancy testing in clinical trials; version 1.1 of 21/09/2020. Personne referred to sections L. 1121-5, L. 1121-7 and L1121-8 of the Public Health Code. Pregnant, parturient or breastfeeding mother Minor (unassecipated) An adult subject to a legal protection measure (tutelage, curate, safeguarding of justice) Adult person undying to express consent Persons deprived of liberty by judicial or administrative decision, persons receiving psychiatric care under sections L. 3212-1 and L. 32131. Vaccination during the 4 weeks (28 days) prior to the first vaccination in the trial Previous vaccination with another investigational vaccine Subjects who have received immunoglobulins, blood or blood derivatives within the last 3 months. Known or suspected congenital or acquired immunodeficiency; immunosuppressive therapy within the last 6 months, such as cancer chemotherapy or radiotherapy; long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the last 3 months). Acute respiratory infection or severe acute febrile illness (temperature ≥ 38.0°C), or a systemic reaction that may be of significant risk with vaccination in the month prior to inclusion.

12. IPD Sharing Statement

Learn more about this trial

Evaluation of Intradermal Hepatitis B Vaccine After IMIQUIMOD's Application, in Cirrhotics Who Did Not Respond to the Usual Vaccine Regimen

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