Hepatitis B
Conditions
Brief summary
This study evaluates the safety and immunogenicity of FP-02.2, a new therapeutic Hepatitis B vaccine, administered as an add-on therapy to entecavir or tenofovir.
Detailed description
This study evaluates the safety and immunogenicity of FP-02.2, a new therapeutic Hepatitis B vaccine, administered as an add-on therapy to entecavir or tenofovir. HBeAg-negative subjects will be randomized to receive low or high dose vaccine, in the presence or absence of IC31® adjuvant, or to receive placebo or IC31® adjuvant alone.
Interventions
BIOLOGICALFP-02.2 Vaccine
Synthetic Peptide Hepatitis B Vaccine
OTHERPlacebo
Placebo
OTHERIC31® Adjuvant
IC31® Adjuvant
Sponsors
Altimmune, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Male and female subjects aged 18-65 years. 2. Diagnosed with chronic hepatitis B defined as HBsAg positive for at least 24 months. 3. Subject has received entecavir or tenofovir for at least 2 years with a stable dose for at least 6 months prior to screening. 4. HBeAg negative for at least 2 years prior to inclusion in the study. 5. HBV DNA \<50 IU/mL for ≥ 12 months 6. ALT/AST ≤ 1.5 x ULN via the local laboratory at the Screening Visit 7. Able to give written informed consent to participate 8. Females should fulfil one of the following criteria: 1. At least one year menopausal 2. Surgically sterile 3. Same-sex relationship 4. WOCBP not surgically sterilized or with laboratory confirmed menopausal status are required to use a highly effective contraceptive measure with low used dependency from screening until one menstrual cycle after the last dose of IMP (Day 58) such as: * Combined (oestrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation * Progestogen-only hormonal contraception implants associated with inhibition of ovulation * Intrauterine device (IUD) * Intrauterine hormone-releasing system (IUS) * Bilateral tubal occlusion * Vasectomised partner - must have had medical assessment of successful surgery. From screening until one menstrual cycle after the last dose of IMP (day 57). Subjects who practice true abstinence or who exclusively have same sex partners need not use contraception, provided it is in line with their preferred and usual lifestyle. Periodic abstinence (eg calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Should any such subject stop practicing true abstinence, they must use contraception as described above. Males should fulfil one of the following criteria: * Surgically sterile * Willing to abstain from sexual intercourse or use a reliable form of contraception (e.g. condom), if having sex with a pregnant or non-pregnant woman of childbearing potential, from screening until 3 months after the final dose of IMP. * Surgically sterilised or post-menopausal female partner or same-sex relationship.
Exclusion criteria
1. Liver disease other than chronic hepatitis B (a diagnosis of steatosis is permitted providing inclusion criterion 6 is met). 2. Evidence of Liver cirrhosis on Fibroscan screening (Liver cirrhosis is defined as a Fibroscan measurement of \>11.5 KPa), or previous history or evidence of cirrhosis on radiological imaging, Fibroscan or liver biopsy. 3. Positive serology for HIV-1 or HIV-2 or HCV or HDV antibodies. 4. Immunodeficient or autoimmune conditions due to disease or medication e.g. systemic steroids within previous 12 weeks. (Topical or inhaled steroids are permissible). 5. Clinically relevant co-morbidity, e.g. autoimmune disease. 6. Clinically relevant anaemia or leukopenia in the opinion of the investigator. 7. Cancer or treatment for cancer within 3 years prior to screening excluding basal cell carcinoma of the skin, which is allowed. 8. Known or suspected intolerance or hypersensitivity to the IMP or closely related compounds or any of the stated ingredients. 9. Receipt of any IMP within 90 days prior to screening or currently receiving IMP or intent to receive IMP. 10. Current substance or alcohol abuse that in the opinion of the Investigator would interfere with compliance or with interpretation of study results. 11. Any condition that in the opinion of the Investigator might interfere with study objectives. 12. Pregnant or breastfeeding. 13. Subjects should not have received, during the 6 month period prior to screening, any medications or other treatments that may adversely affect the immune system such as allergy injections, immunoglobulins, interferons, cytotoxic drugs or other drugs known to be frequently associated with significant major organ toxicity, or systemic corticosteroids (oral or injectable). Immunosuppressive treatment such as azathioprine or mercaptopurine is not permitted 6 months prior to screening. 14. Administration of live vaccines (such as live influenza vaccinations or live travel vaccinations) from 10 days prior to the screening visit until Day 85.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Throughout the study to Day 85 | Incidences of all TEAEs, IP related TEAEs, severe TEAEs, TEAEs leading to discontinuation of IP, and serious TEAEs, |
| Number of Subjects With Local Injection Site Reactions | Days 1 through 64 | Incidence of local injection site reactions occurring up to 7 days after each injection |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immunological Response | Change from baseline to Day 85 | IFN-gamma ELISpot assay specific for FP-02.2 peptides using cryopreserved PBMCs |
Countries
South Korea, United Kingdom
Participant flow
Recruitment details
Phase 1, randomised, double-blind, placebo-controlled clinical trial to evaluate the safety, tolerability, and immunogenicity of Vaccine FP-02.2 in hepatitis B e-antigen (HBeAg)-negative patients chronically infected with HBV aged 18 to 65 years who had been receiving entecavir or tenofovir for ≥ 2 years
Pre-assignment details
Subjects who met all inclusion and no exclusion criteria and provided written informed consent were enrolled within 28 days of Screening. Approximately 10 subjects were enrolled in each of 6 treatment groups in 3 sequential cohorts
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo component administered by IM injection on Days 1, 29, and 57
Placebo: Placebo | 10 |
| IC31® Adjuvant IC31® Adjuvant alone administered by IM injection on Days 1, 29, and 57
IC31® Adjuvant: IC31® Adjuvant | 10 |
| FP-02.2 Low Dose A low dose (150 µg/peptide) of the FP-02.2 vaccine administered by IM injection on Days 1, 29, and 57
FP-02.2 Vaccine: Synthetic Peptide Hepatitis B Vaccine | 10 |
| FP-02.2 Low Dose With IC31® Adjuvant A low dose (150 µg/peptide) of the FP-02.2 vaccine with IC31® Adjuvant administered by IM injection on Days 1, 29, and 57
FP-02.2 Vaccine: Synthetic Peptide Hepatitis B Vaccine
IC31® Adjuvant: IC31® Adjuvant | 10 |
| FP-02.2 High Dose A high dose (500 µg/peptide) of the FP-02.2 vaccine administered by IM injection on Days 1, 29, and 57
FP-02.2 Vaccine: Synthetic Peptide Hepatitis B Vaccine | 10 |
| FP-02.2 High Dose With IC31® Adjuvant A high dose (500 µg/peptide) of the FP-02.2 vaccine with IC31® Adjuvant administered by IM injection on Days 1, 29, and 57
FP-02.2 Vaccine: Synthetic Peptide Hepatitis B Vaccine
IC31® Adjuvant: IC31® Adjuvant | 11 |
| Total | 61 |
Baseline characteristics
| Characteristic | Placebo | Total | FP-02.2 High Dose With IC31® Adjuvant | FP-02.2 High Dose | FP-02.2 Low Dose With IC31® Adjuvant | FP-02.2 Low Dose | IC31® Adjuvant |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 47.7 years STANDARD_DEVIATION 9.62 | 47.8 years STANDARD_DEVIATION 8.41 | 48.9 years STANDARD_DEVIATION 9.8 | 47.6 years STANDARD_DEVIATION 6.96 | 50.0 years STANDARD_DEVIATION 7.63 | 41.5 years STANDARD_DEVIATION 6.75 | 50.9 years STANDARD_DEVIATION 7.61 |
| Body Mass Index | 27.1 kg/m^2 STANDARD_DEVIATION 4.87 | 25.9 kg/m^2 STANDARD_DEVIATION 3.73 | 23.7 kg/m^2 STANDARD_DEVIATION 1.99 | 26.6 kg/m^2 STANDARD_DEVIATION 3.89 | 26.8 kg/m^2 STANDARD_DEVIATION 3.48 | 26.6 kg/m^2 STANDARD_DEVIATION 3.35 | 24.6 kg/m^2 STANDARD_DEVIATION 3.91 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 60 Participants | 10 Participants | 10 Participants | 10 Participants | 10 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Liver stiffness by Fibroscan | 5.8 kPa STANDARD_DEVIATION 1.32 | 5.2 kPa STANDARD_DEVIATION 1.57 | 4.6 kPa STANDARD_DEVIATION 1.06 | 6.1 kPa STANDARD_DEVIATION 2.25 | 5.4 kPa STANDARD_DEVIATION 1.34 | 4.9 kPa STANDARD_DEVIATION 1.41 | 4.2 kPa STANDARD_DEVIATION 1.24 |
| Race Asian | 3 Participants | 42 Participants | 11 Participants | 7 Participants | 7 Participants | 5 Participants | 9 Participants |
| Race Black or African American | 1 Participants | 6 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants | 0 Participants |
| Race Multiple | 4 Participants | 7 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race Other | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race White | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Region of Enrollment South Korea | 2 participants | 30 participants | 11 participants | 4 participants | 5 participants | 0 participants | 8 participants |
| Region of Enrollment United Kingdom | 8 participants | 31 participants | 0 participants | 6 participants | 5 participants | 10 participants | 2 participants |
| Sex: Female, Male Female | 1 Participants | 13 Participants | 3 Participants | 3 Participants | 0 Participants | 1 Participants | 5 Participants |
| Sex: Female, Male Male | 9 Participants | 48 Participants | 8 Participants | 7 Participants | 10 Participants | 9 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 11 |
| other Total, other adverse events | 9 / 10 | 3 / 10 | 7 / 10 | 7 / 10 | 4 / 10 | 5 / 11 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 10 | 1 / 11 |
Outcome results
Primary
Number of Subjects With Local Injection Site Reactions
Incidence of local injection site reactions occurring up to 7 days after each injection
Time frame: Days 1 through 64
Population: Safety population (all subjects who received IP)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Subjects With Local Injection Site Reactions | Pain/tenderness (on pressure) | 2 Participants |
| Placebo | Number of Subjects With Local Injection Site Reactions | Any injection site reaction | 2 Participants |
| Placebo | Number of Subjects With Local Injection Site Reactions | Erythema/redness | 2 Participants |
| Placebo | Number of Subjects With Local Injection Site Reactions | Wheal(s) | 1 Participants |
| Placebo | Number of Subjects With Local Injection Site Reactions | Induration/hardening | 2 Participants |
| Placebo | Number of Subjects With Local Injection Site Reactions | Pain (without pressure) | 1 Participants |
| Placebo | Number of Subjects With Local Injection Site Reactions | Swelling | 2 Participants |
| Placebo | Number of Subjects With Local Injection Site Reactions | Burning sensation | 1 Participants |
| IC31® Adjuvant | Number of Subjects With Local Injection Site Reactions | Swelling | 0 Participants |
| IC31® Adjuvant | Number of Subjects With Local Injection Site Reactions | Erythema/redness | 0 Participants |
| IC31® Adjuvant | Number of Subjects With Local Injection Site Reactions | Wheal(s) | 0 Participants |
| IC31® Adjuvant | Number of Subjects With Local Injection Site Reactions | Burning sensation | 0 Participants |
| IC31® Adjuvant | Number of Subjects With Local Injection Site Reactions | Any injection site reaction | 1 Participants |
| IC31® Adjuvant | Number of Subjects With Local Injection Site Reactions | Pain/tenderness (on pressure) | 0 Participants |
| IC31® Adjuvant | Number of Subjects With Local Injection Site Reactions | Pain (without pressure) | 0 Participants |
| IC31® Adjuvant | Number of Subjects With Local Injection Site Reactions | Induration/hardening | 1 Participants |
| FP-02.2 Low Dose | Number of Subjects With Local Injection Site Reactions | Pain (without pressure) | 6 Participants |
| FP-02.2 Low Dose | Number of Subjects With Local Injection Site Reactions | Swelling | 2 Participants |
| FP-02.2 Low Dose | Number of Subjects With Local Injection Site Reactions | Wheal(s) | 0 Participants |
| FP-02.2 Low Dose | Number of Subjects With Local Injection Site Reactions | Any injection site reaction | 6 Participants |
| FP-02.2 Low Dose | Number of Subjects With Local Injection Site Reactions | Burning sensation | 0 Participants |
| FP-02.2 Low Dose | Number of Subjects With Local Injection Site Reactions | Erythema/redness | 0 Participants |
| FP-02.2 Low Dose | Number of Subjects With Local Injection Site Reactions | Induration/hardening | 0 Participants |
| FP-02.2 Low Dose | Number of Subjects With Local Injection Site Reactions | Pain/tenderness (on pressure) | 5 Participants |
| FP-02.2 Low Dose With IC31® Adjuvant | Number of Subjects With Local Injection Site Reactions | Swelling | 0 Participants |
| FP-02.2 Low Dose With IC31® Adjuvant | Number of Subjects With Local Injection Site Reactions | Burning sensation | 3 Participants |
| FP-02.2 Low Dose With IC31® Adjuvant | Number of Subjects With Local Injection Site Reactions | Induration/hardening | 0 Participants |
| FP-02.2 Low Dose With IC31® Adjuvant | Number of Subjects With Local Injection Site Reactions | Any injection site reaction | 6 Participants |
| FP-02.2 Low Dose With IC31® Adjuvant | Number of Subjects With Local Injection Site Reactions | Wheal(s) | 0 Participants |
| FP-02.2 Low Dose With IC31® Adjuvant | Number of Subjects With Local Injection Site Reactions | Pain (without pressure) | 3 Participants |
| FP-02.2 Low Dose With IC31® Adjuvant | Number of Subjects With Local Injection Site Reactions | Pain/tenderness (on pressure) | 4 Participants |
| FP-02.2 Low Dose With IC31® Adjuvant | Number of Subjects With Local Injection Site Reactions | Erythema/redness | 1 Participants |
| FP-02.2 High Dose | Number of Subjects With Local Injection Site Reactions | Induration/hardening | 1 Participants |
| FP-02.2 High Dose | Number of Subjects With Local Injection Site Reactions | Any injection site reaction | 5 Participants |
| FP-02.2 High Dose | Number of Subjects With Local Injection Site Reactions | Pain/tenderness (on pressure) | 5 Participants |
| FP-02.2 High Dose | Number of Subjects With Local Injection Site Reactions | Pain (without pressure) | 3 Participants |
| FP-02.2 High Dose | Number of Subjects With Local Injection Site Reactions | Swelling | 0 Participants |
| FP-02.2 High Dose | Number of Subjects With Local Injection Site Reactions | Erythema/redness | 0 Participants |
| FP-02.2 High Dose | Number of Subjects With Local Injection Site Reactions | Wheal(s) | 0 Participants |
| FP-02.2 High Dose | Number of Subjects With Local Injection Site Reactions | Burning sensation | 2 Participants |
| FP-02.2 High Dose With IC31® Adjuvant | Number of Subjects With Local Injection Site Reactions | Any injection site reaction | 5 Participants |
| FP-02.2 High Dose With IC31® Adjuvant | Number of Subjects With Local Injection Site Reactions | Induration/hardening | 0 Participants |
| FP-02.2 High Dose With IC31® Adjuvant | Number of Subjects With Local Injection Site Reactions | Erythema/redness | 1 Participants |
| FP-02.2 High Dose With IC31® Adjuvant | Number of Subjects With Local Injection Site Reactions | Pain/tenderness (on pressure) | 1 Participants |
| FP-02.2 High Dose With IC31® Adjuvant | Number of Subjects With Local Injection Site Reactions | Burning sensation | 0 Participants |
| FP-02.2 High Dose With IC31® Adjuvant | Number of Subjects With Local Injection Site Reactions | Wheal(s) | 0 Participants |
| FP-02.2 High Dose With IC31® Adjuvant | Number of Subjects With Local Injection Site Reactions | Pain (without pressure) | 4 Participants |
| FP-02.2 High Dose With IC31® Adjuvant | Number of Subjects With Local Injection Site Reactions | Swelling | 0 Participants |
Primary
Number of Subjects With Treatment Emergent Adverse Events (TEAEs)
Incidences of all TEAEs, IP related TEAEs, severe TEAEs, TEAEs leading to discontinuation of IP, and serious TEAEs,
Time frame: Throughout the study to Day 85
Population: Safety population (all subjects who received IP)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | TEAE leading to IP discontinuation | 0 Participants |
| Placebo | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Possibly treatment related TEAE | 3 Participants |
| Placebo | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Any treatment emergent adverse event (TEAE) | 9 Participants |
| Placebo | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Severe TEAE | 0 Participants |
| Placebo | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Serious adverse event | 0 Participants |
| IC31® Adjuvant | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Severe TEAE | 0 Participants |
| IC31® Adjuvant | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | TEAE leading to IP discontinuation | 0 Participants |
| IC31® Adjuvant | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Possibly treatment related TEAE | 1 Participants |
| IC31® Adjuvant | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Serious adverse event | 0 Participants |
| IC31® Adjuvant | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Any treatment emergent adverse event (TEAE) | 3 Participants |
| FP-02.2 Low Dose | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Possibly treatment related TEAE | 5 Participants |
| FP-02.2 Low Dose | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Serious adverse event | 0 Participants |
| FP-02.2 Low Dose | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | TEAE leading to IP discontinuation | 0 Participants |
| FP-02.2 Low Dose | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Severe TEAE | 0 Participants |
| FP-02.2 Low Dose | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Any treatment emergent adverse event (TEAE) | 7 Participants |
| FP-02.2 Low Dose With IC31® Adjuvant | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Severe TEAE | 1 Participants |
| FP-02.2 Low Dose With IC31® Adjuvant | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Serious adverse event | 0 Participants |
| FP-02.2 Low Dose With IC31® Adjuvant | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Possibly treatment related TEAE | 5 Participants |
| FP-02.2 Low Dose With IC31® Adjuvant | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Any treatment emergent adverse event (TEAE) | 7 Participants |
| FP-02.2 Low Dose With IC31® Adjuvant | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | TEAE leading to IP discontinuation | 0 Participants |
| FP-02.2 High Dose | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | TEAE leading to IP discontinuation | 0 Participants |
| FP-02.2 High Dose | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Any treatment emergent adverse event (TEAE) | 4 Participants |
| FP-02.2 High Dose | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Possibly treatment related TEAE | 1 Participants |
| FP-02.2 High Dose | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Severe TEAE | 0 Participants |
| FP-02.2 High Dose | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Serious adverse event | 0 Participants |
| FP-02.2 High Dose With IC31® Adjuvant | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Possibly treatment related TEAE | 1 Participants |
| FP-02.2 High Dose With IC31® Adjuvant | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Any treatment emergent adverse event (TEAE) | 6 Participants |
| FP-02.2 High Dose With IC31® Adjuvant | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | TEAE leading to IP discontinuation | 1 Participants |
| FP-02.2 High Dose With IC31® Adjuvant | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Serious adverse event | 1 Participants |
| FP-02.2 High Dose With IC31® Adjuvant | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Severe TEAE | 0 Participants |
Secondary
Immunological Response
IFN-gamma ELISpot assay specific for FP-02.2 peptides using cryopreserved PBMCs
Time frame: Change from baseline to Day 85
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Immunological Response | 166.7 spot forming units/ 10^6 PBMC |
| IC31® Adjuvant | Immunological Response | 1683.3 spot forming units/ 10^6 PBMC |
| FP-02.2 Low Dose | Immunological Response | 900 spot forming units/ 10^6 PBMC |
| FP-02.2 Low Dose With IC31® Adjuvant | Immunological Response | 5608.3 spot forming units/ 10^6 PBMC |
| FP-02.2 High Dose | Immunological Response | 1433.3 spot forming units/ 10^6 PBMC |
| FP-02.2 High Dose With IC31® Adjuvant | Immunological Response | 4804.2 spot forming units/ 10^6 PBMC |