Effectiveness and Safety of Intra-Dermal Hepatitis B Vaccination after a local application of cream, called IMIQUIMOD, in cirrhotic patients who did not respond to the conventional (intra-muscular) vaccine regimen.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

CHRU De Nancy

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

8 Jul 2022 → 22 Jan 2025

Decision date (initial)

2024-06-26

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

CHRU de Nancy

External identifiers

EU CT number

2024-514605-61-00

EudraCT number

2021-000644-22

ClinicalTrials.gov

NCT05028322

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Pharmacodynamic

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

Secondary objectives 5

1. 1) 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
2. 2) Describe the proportion of patients with an anti-HB antibody level XML File Identifier: 4OFx7yPD7y2aMzwWhccyURJR8r4= Page 18/31 greater than 10mUI/mL at 6 months of the first injection (M6) with a vaccine regimen according to the vaccine strategy
3. 3) Describe the evolution of the level of anti-HBs antibodies between 2 successive visits according to the vaccine strategy;
4. 4) Describe the rate of adverse events (by severity level) following the injection of a dose of intradermal vaccine
5. 5) Describe the rate of adverse events (by severity level) following the injection of an intradermal vaccine dose after prior application of Imiquimod

Conditions and MedDRA coding

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)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 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 1

1. 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. Verification of the absence of a current pregnancy will be carried out by a urinary Beta HCG assay. It should be noted that the vast majority of cirrhotic patients followed up in hepatology consultations are women over 60 years of age and menopausal. 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. 3213- 1. - 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. For each vaccine strategy: proportion of patients with an anti-HBs antibody level greater than 10mUI/mL at M7 from the initial injection.

Secondary endpoints 5

1. 1) For each vaccine strategy: proportion of patients for whom an anti- HBs antibody level greater than 10mUI/mL is found at M1 from the initial injection.
2. 2) For each vaccine strategy: proportion of patients for whom an anti- HBs antibody level greater than 10mUI/mL is found at M6 from the initial injection.
3. 3) For each vaccine strategy, the evolution of the HB antibody title (in mUI/mL) will be considered: - Between dosages made at M0 and M1 (before versus 1 month of the first injection) - Between dosages at M1 and M6 (before versus 5 months of the 2nd injection) - Between dosages at M6 and M7 (before versus 1 month of the 3rd injection)
4. 4) In patients who received the intradermal vaccine without prior application of Imiquimod: number of side effects and sevre side effects immediately or delayed at the injection site in relation to the number of intradermal injections performed in these patients;
5. 5) In patients who received the intradermal vaccine after prior application of Imiquimod: the number of side effects and severe side effects immediately or delayed at the Imiquimod application area and injection site in relation to the number of intradermal injections after prior application of Imiquimod in these patients.

Investigational products

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

Test 2

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

CHRU De Nancy

Sponsor organisation

CHRU De Nancy

Address

Co N°34, 29 Avenue Du Mal De Lattre De Tassigny, Bp 60034 29 Avenue Du Mal De Lattre De Tassigny Bp 60034

City

Nancy Cedex

Postcode

54035

Country

France

Scientific contact point

Organisation

CHRU De Nancy

Contact name

BERNARD Yohann

Public contact point

Organisation

CHRU De Nancy

Contact name

BERNARD Yohann

Locations

1 EU/EEA country · 1 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 2 files

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

Application history

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