Trial Outcomes & Findings for Safety and Immunogenicity of HBAI20 Hepatitis B Vaccine in Naive Adults and Non-responders (NCT NCT02540538)
NCT ID: NCT02540538
Last Updated: 2018-12-19
Results Overview
Subjects will be given a diary for 4 days after the first and second vaccination. Dairy: Local reactions at injection site: Pain (1 to 4), Impaired movement of injected arm (1 to 4), Redness/erythema (cm), Swelling (cm), Induration (cm) General/Systemic adverse events: Fever (temperature measurement), Headache (1 to 4), Fatigue (1 to 4), Muscle pain (1 to 4), Skin rash (1 to 4), Vomiting (1 to 4), Diarrhea (1 to 4). Record medication taken during the study (up to 7 months after the first vaccination).
COMPLETED
PHASE1
34 participants
Up to 7 months after first vaccination.
2018-12-19
Participant Flow
This phase I study involved two trials: a double-blinded RCT in naïve participants and an open-label study in a cohort of true non-responders. At the first visit, a physical examination was performed and blood and urine sampling were taken, and informed written consent was required to participate in the study.
In RCT, 27 recruits, 3 naïve participants exclusions: * 1 with liver LFTs abnormalities * 1 with anti-HBs-AB \>10 mIU/mL * 1 with suspicion of Cushing's syndrome Thus, 24 healthy participants were included. In the open-label study, 10 true non-responders were screened, then included. All participants were between 18 and 59 years of age.
Participant milestones
| Measure |
HB Vaccine Naive - HBVaxPro
Subjects have never been vaccinated with a Hepatitis B vaccine. Subjects are vaccinated with Hepatitis B vaccine HBVaxPro-10ug at day 0, 30, and 180.
HBVaxPro: 3 vaccinations with HBVaxPro-10ug at 0, 30, and 180 days.
|
HB Vaccine Naive - HBAI20
Subjects have never been vaccinated with a Hepatitis B vaccine. Subjects are vaccinated with Hepatitis B vaccine HBAI20 at day 0 and 30, and Hepatitis B vaccine HBVaxPro-10ug at day 180.
HBAI20: 2 vaccinations with HBAI20 at 0 and 30 days and 1 vaccination with HBVaxPro-10ug at 180 days.
|
Non-responders - HBAI20
Subjects have been vaccinated 6 times with a Hepatitis B vaccine without developing a protective immune response, measured as anti Hepatitis B surface antigen antibodies, superior to 10mIU/ml.
Subjects are vaccinated with Hepatitis B vaccine HBAI20 at day 0 and 30, and Hepatitis B vaccine HBVaxPro-10ug at day 180.
HBAI20: 2 vaccinations with HBAI20 at 0 and 30 days and 1 vaccination with HBVaxPro-10ug at 180 days.
|
|---|---|---|---|
|
Overall Study
STARTED
|
12
|
12
|
10
|
|
Overall Study
COMPLETED
|
12
|
11
|
10
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
0
|
Reasons for withdrawal
| Measure |
HB Vaccine Naive - HBVaxPro
Subjects have never been vaccinated with a Hepatitis B vaccine. Subjects are vaccinated with Hepatitis B vaccine HBVaxPro-10ug at day 0, 30, and 180.
HBVaxPro: 3 vaccinations with HBVaxPro-10ug at 0, 30, and 180 days.
|
HB Vaccine Naive - HBAI20
Subjects have never been vaccinated with a Hepatitis B vaccine. Subjects are vaccinated with Hepatitis B vaccine HBAI20 at day 0 and 30, and Hepatitis B vaccine HBVaxPro-10ug at day 180.
HBAI20: 2 vaccinations with HBAI20 at 0 and 30 days and 1 vaccination with HBVaxPro-10ug at 180 days.
|
Non-responders - HBAI20
Subjects have been vaccinated 6 times with a Hepatitis B vaccine without developing a protective immune response, measured as anti Hepatitis B surface antigen antibodies, superior to 10mIU/ml.
Subjects are vaccinated with Hepatitis B vaccine HBAI20 at day 0 and 30, and Hepatitis B vaccine HBVaxPro-10ug at day 180.
HBAI20: 2 vaccinations with HBAI20 at 0 and 30 days and 1 vaccination with HBVaxPro-10ug at 180 days.
|
|---|---|---|---|
|
Overall Study
Pregnancy
|
0
|
1
|
0
|
Baseline Characteristics
Safety and Immunogenicity of HBAI20 Hepatitis B Vaccine in Naive Adults and Non-responders
Baseline characteristics by cohort
| Measure |
HB Vaccine Naive - HBVaxPro
n=12 Participants
Subjects have never been vaccinated with a Hepatitis B vaccine. Subjects are vaccinated with Hepatitis B vaccine HBVaxPro-10ug at day 0, 30, and 180.
HBVaxPro: 3 vaccinations with HBVaxPro-10ug at 0, 30, and 180 days.
|
HB Vaccine Naive - HBAI20
n=12 Participants
Subjects have never been vaccinated with a Hepatitis B vaccine. Subjects are vaccinated with Hepatitis B vaccine HBAI20 at day 0 and 30, and Hepatitis B vaccine HBVaxPro-10ug at day 180.
HBAI20: 2 vaccinations with HBAI20 at 0 and 30 days and 1 vaccination with HBVaxPro-10ug at 180 days.
|
Non-responders - HBAI20
n=10 Participants
Subjects have been vaccinated 6 times with a Hepatitis B vaccine without developing a protective immune response, measured as anti Hepatitis B surface antigen antibodies, superior to 10mIU/ml.
Subjects are vaccinated with Hepatitis B vaccine HBAI20 at day 0 and 30, and Hepatitis B vaccine HBVaxPro-10ug at day 180.
HBAI20: 2 vaccinations with HBAI20 at 0 and 30 days and 1 vaccination with HBVaxPro-10ug at 180 days.
|
Total
n=34 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
29 Years (IQR)
n=93 Participants
|
29 Years (IQR)
n=4 Participants
|
48 Years (IQR)
n=27 Participants
|
34 Years (IQR)
n=483 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=93 Participants
|
9 Participants
n=4 Participants
|
5 Participants
n=27 Participants
|
22 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
5 Participants
n=27 Participants
|
12 Participants
n=483 Participants
|
|
BMI
|
25 kg/m^2
n=93 Participants
|
23 kg/m^2
n=4 Participants
|
29 kg/m^2
n=27 Participants
|
25 kg/m^2
n=483 Participants
|
|
Anti-HBs Titers < 2 IU/ml
|
12 Participants
n=93 Participants
|
12 Participants
n=4 Participants
|
8 Participants
n=27 Participants
|
32 Participants
n=483 Participants
|
PRIMARY outcome
Timeframe: Up to 7 months after first vaccination.Population: RCT: 27 participants screened, 3 excluded: 1 with LFTs abnormalities, 1 anti-HBs titre \>10 mIU/mL, 1 suspected Cushing's syndrome. 24 included. Open-Label: 10 screened and included.
Subjects will be given a diary for 4 days after the first and second vaccination. Dairy: Local reactions at injection site: Pain (1 to 4), Impaired movement of injected arm (1 to 4), Redness/erythema (cm), Swelling (cm), Induration (cm) General/Systemic adverse events: Fever (temperature measurement), Headache (1 to 4), Fatigue (1 to 4), Muscle pain (1 to 4), Skin rash (1 to 4), Vomiting (1 to 4), Diarrhea (1 to 4). Record medication taken during the study (up to 7 months after the first vaccination).
Outcome measures
| Measure |
HB Vaccine Naive - HBVaxPro
n=12 Participants
Subjects have never been vaccinated with a Hepatitis B vaccine. Subjects are vaccinated with Hepatitis B vaccine HBVaxPro-10ug at day 0, 30, and 180.
HBVaxPro: 3 vaccinations with HBVaxPro-10ug at 0, 30, and 180 days.
|
HB Vaccine Naive - HBAI20
n=12 Participants
Subjects have never been vaccinated with a Hepatitis B vaccine. Subjects are vaccinated with Hepatitis B vaccine HBAI20 at day 0 and 30, and Hepatitis B vaccine HBVaxPro-10ug at day 180.
HBAI20: 2 vaccinations with HBAI20 at 0 and 30 days and 1 vaccination with HBVaxPro-10ug at 180 days.
|
Non-responders - HBAI20
n=10 Participants
Subjects have been vaccinated 6 times with a Hepatitis B vaccine without developing a protective immune response, measured as anti Hepatitis B surface antigen antibodies, superior to 10mIU/ml.
Subjects are vaccinated with Hepatitis B vaccine HBAI20 at day 0 and 30, and Hepatitis B vaccine HBVaxPro-10ug at day 180.
HBAI20: 2 vaccinations with HBAI20 at 0 and 30 days and 1 vaccination with HBVaxPro-10ug at 180 days.
|
|---|---|---|---|
|
Subjects With Local and/or General Adverse Events Irrespective of Severity
Diarrhea
|
2 Participants
|
3 Participants
|
0 Participants
|
|
Subjects With Local and/or General Adverse Events Irrespective of Severity
Pain at the injection site
|
8 Participants
|
9 Participants
|
7 Participants
|
|
Subjects With Local and/or General Adverse Events Irrespective of Severity
Impaired movement of injected arm
|
7 Participants
|
8 Participants
|
4 Participants
|
|
Subjects With Local and/or General Adverse Events Irrespective of Severity
Redness/Erythema
|
6 Participants
|
4 Participants
|
4 Participants
|
|
Subjects With Local and/or General Adverse Events Irrespective of Severity
Swelling
|
3 Participants
|
2 Participants
|
0 Participants
|
|
Subjects With Local and/or General Adverse Events Irrespective of Severity
Induration
|
1 Participants
|
1 Participants
|
4 Participants
|
|
Subjects With Local and/or General Adverse Events Irrespective of Severity
Fever
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Subjects With Local and/or General Adverse Events Irrespective of Severity
Headache
|
4 Participants
|
3 Participants
|
1 Participants
|
|
Subjects With Local and/or General Adverse Events Irrespective of Severity
Fatigue
|
5 Participants
|
3 Participants
|
3 Participants
|
|
Subjects With Local and/or General Adverse Events Irrespective of Severity
Myalgia
|
9 Participants
|
9 Participants
|
7 Participants
|
|
Subjects With Local and/or General Adverse Events Irrespective of Severity
Vomiting
|
0 Participants
|
1 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Up to 7 months after first vaccinationPopulation: RCT: 27 participants screened, 3 excluded: 1 with LFTs abnormalities, 1 anti-HBs titre \>10 mIU/mL, 1 suspected Cushing's syndrome. 24 included. Open-Label: 10 screened and included.
Subjects will be given a diary for 4 days after the first and second vaccination. Dairy: Local reactions at injection site: Pain (1 to 4), Impaired movement of injected arm (1 to 4), Redness/erythema (cm), Swelling (cm), Induration (cm) General/Systemic adverse events: Fever (temperature measurement), Headache (1 to 4), Fatigue (1 to 4), Muscle pain (1 to 4), Skin rash (1 to 4), Vomiting (1 to 4), Diarrhea (1 to 4). Record medication taken during the study (up to 7 months after the first vaccination). The laboratory parameters analysed at day 10, 30, 40, 60, 180, and 210 are: Hematology: Hematocrit, Hemoglobin, RBC count, WBC count, Platelet count, Neutrophils, Eosinophils, Basophils, Lymphocytes, and Monocytes. Biochemistry: Creatinine, Albumin, Alkaline Phosphatase, Total Bilirubin, ALT (GPT), AST (GOT), Gamma-Gt, C-Reactive Protein, and TSH/FT4. Urinalysis (day 10, 40, and 210): Clarity, Color, Specific gravity, Leukocytes, Nitrite, pH, Erythrocytes, Albumin, and Glucose.
Outcome measures
| Measure |
HB Vaccine Naive - HBVaxPro
n=12 Participants
Subjects have never been vaccinated with a Hepatitis B vaccine. Subjects are vaccinated with Hepatitis B vaccine HBVaxPro-10ug at day 0, 30, and 180.
HBVaxPro: 3 vaccinations with HBVaxPro-10ug at 0, 30, and 180 days.
|
HB Vaccine Naive - HBAI20
n=12 Participants
Subjects have never been vaccinated with a Hepatitis B vaccine. Subjects are vaccinated with Hepatitis B vaccine HBAI20 at day 0 and 30, and Hepatitis B vaccine HBVaxPro-10ug at day 180.
HBAI20: 2 vaccinations with HBAI20 at 0 and 30 days and 1 vaccination with HBVaxPro-10ug at 180 days.
|
Non-responders - HBAI20
n=10 Participants
Subjects have been vaccinated 6 times with a Hepatitis B vaccine without developing a protective immune response, measured as anti Hepatitis B surface antigen antibodies, superior to 10mIU/ml.
Subjects are vaccinated with Hepatitis B vaccine HBAI20 at day 0 and 30, and Hepatitis B vaccine HBVaxPro-10ug at day 180.
HBAI20: 2 vaccinations with HBAI20 at 0 and 30 days and 1 vaccination with HBVaxPro-10ug at 180 days.
|
|---|---|---|---|
|
Subjects With Local and/or General SEVERE Adverse Events
Severe pain at injection site
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Subjects With Local and/or General SEVERE Adverse Events
Severe impaired movement of injected arm
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Subjects With Local and/or General SEVERE Adverse Events
Severe redness
|
1 Participants
|
0 Participants
|
1 Participants
|
|
Subjects With Local and/or General SEVERE Adverse Events
Sever swelling
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Subjects With Local and/or General SEVERE Adverse Events
Severe induration
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Subjects With Local and/or General SEVERE Adverse Events
Fever
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Subjects With Local and/or General SEVERE Adverse Events
Headache
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Subjects With Local and/or General SEVERE Adverse Events
Fatigue
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Subjects With Local and/or General SEVERE Adverse Events
Myalgia
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Subjects With Local and/or General SEVERE Adverse Events
Vomiting
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Subjects With Local and/or General SEVERE Adverse Events
Diarrhea
|
0 Participants
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Day 0, 10, 30, 40, 60, 180, and 210Population: RCT: 27 participants screened, 3 excluded: 1 with LFTs abnormalities, 1 anti-HBs titre \>10 mIU/mL, 1 suspected Cushing's syndrome. 24 included. Open-Label: 10 screened and included.
Seroprotection at visit number 7, one month after the third vaccination. Anti-HBs antibodies were assayed from serum using a routine chemiluminescence assay (Anti-HBs, Cobas 8000, Roche, Germany). Titres \>10 mIU/mL were considered to be seroprotective.
Outcome measures
| Measure |
HB Vaccine Naive - HBVaxPro
n=12 Participants
Subjects have never been vaccinated with a Hepatitis B vaccine. Subjects are vaccinated with Hepatitis B vaccine HBVaxPro-10ug at day 0, 30, and 180.
HBVaxPro: 3 vaccinations with HBVaxPro-10ug at 0, 30, and 180 days.
|
HB Vaccine Naive - HBAI20
n=12 Participants
Subjects have never been vaccinated with a Hepatitis B vaccine. Subjects are vaccinated with Hepatitis B vaccine HBAI20 at day 0 and 30, and Hepatitis B vaccine HBVaxPro-10ug at day 180.
HBAI20: 2 vaccinations with HBAI20 at 0 and 30 days and 1 vaccination with HBVaxPro-10ug at 180 days.
|
Non-responders - HBAI20
n=10 Participants
Subjects have been vaccinated 6 times with a Hepatitis B vaccine without developing a protective immune response, measured as anti Hepatitis B surface antigen antibodies, superior to 10mIU/ml.
Subjects are vaccinated with Hepatitis B vaccine HBAI20 at day 0 and 30, and Hepatitis B vaccine HBVaxPro-10ug at day 180.
HBAI20: 2 vaccinations with HBAI20 at 0 and 30 days and 1 vaccination with HBVaxPro-10ug at 180 days.
|
|---|---|---|---|
|
Number of Participants With Seroprotection
Day 10
|
0 Participants
|
0 Participants
|
3 Participants
|
|
Number of Participants With Seroprotection
Day 30
|
1 Participants
|
2 Participants
|
1 Participants
|
|
Number of Participants With Seroprotection
Day 40
|
7 Participants
|
11 Participants
|
6 Participants
|
|
Number of Participants With Seroprotection
Day 60
|
9 Participants
|
10 Participants
|
6 Participants
|
|
Number of Participants With Seroprotection
Day 180
|
10 Participants
|
9 Participants
|
7 Participants
|
|
Number of Participants With Seroprotection
Day 210
|
12 Participants
|
12 Participants
|
9 Participants
|
Adverse Events
HB Vaccine Naive - HBVaxPro
HB Vaccine Naive - HBAI20
Non-responders - HBAI20
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
HB Vaccine Naive - HBVaxPro
n=12 participants at risk
Subjects have never been vaccinated with a Hepatitis B vaccine. Subjects are vaccinated with Hepatitis B vaccine HBVaxPro-10ug at day 0, 30, and 180.
HBVaxPro: 3 vaccinations with HBVaxPro-10ug at 0, 30, and 180 days.
|
HB Vaccine Naive - HBAI20
n=12 participants at risk
Subjects have never been vaccinated with a Hepatitis B vaccine. Subjects are vaccinated with Hepatitis B vaccine HBAI20 at day 0 and 30, and Hepatitis B vaccine HBVaxPro-10ug at day 180.
HBAI20: 2 vaccinations with HBAI20 at 0 and 30 days and 1 vaccination with HBVaxPro-10ug at 180 days.
|
Non-responders - HBAI20
n=10 participants at risk
Subjects have been vaccinated 6 times with a Hepatitis B vaccine without developing a protective immune response, measured as anti Hepatitis B surface antigen antibodies, superior to 10mIU/ml.
Subjects are vaccinated with Hepatitis B vaccine HBAI20 at day 0 and 30, and Hepatitis B vaccine HBVaxPro-10ug at day 180.
HBAI20: 2 vaccinations with HBAI20 at 0 and 30 days and 1 vaccination with HBVaxPro-10ug at 180 days.
|
|---|---|---|---|
|
General disorders
Unsolicited symptoms
|
16.7%
2/12 • Up to 7 months after first vaccination
|
33.3%
4/12 • Up to 7 months after first vaccination
|
50.0%
5/10 • Up to 7 months after first vaccination
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place