A single-center, double-blind, randomized, phase I/II dose escalating study to assess the safety, tolerability and immunogenicity of three doses of the therapeutic synthetic long peptide (SLP) vaccine (ISA104) in patients with chronic hepatitis B (cHBV).

Recruitment & Eligibility

Status: Pending

Sex: Not specified

Target Recruitment: 24

Inclusion Criteria

• Chronic HBV.
• Receiving treatment at the time of study entry and for greater than or equal
to 12 months prior to study entry with HBV-active nucleos(t)ides, with
tenofovir- or entecavir-containing therapy: tenofovir disoproxil fumarate
(TDF), tenofovir alafenamide (TAF), or entecavir.
• Positive HBsAg for more than 6 months before screening.
• Negative for HBeAg for more than 6 months before screening.
• HBV DNA < limit of quantification (20 IU/ml; CAP-CTM Roche Cobas).
• Available serum ALT values (within 1x ULN) for 2 different time points 14
days apart during the six months before the first dose of study drug with at
least one of the determinations obtained during the screening period.
• Available liver biopsy or fibroscan within 12 months before inclusion
indicating F0-F1 fibrosis.
• Willing to comply with effective contraception during the study if subject is
male or woman of child bearing potential, up to 12 months after the vaccine
administration.
• Patients must be >= 18 and <= 55 years of age and must be able to give written
informed consent.
• Body mass index (BMI) >= 18.0 and < 32.0 kg/m2.
• Ability to return to the hospital for adequate follow-up as required by this
protocol.
• The ability to communicate well with the Investigator in the Dutch or English
language.
• Written informed consent according to ICH-GCP.
• Willing to comply with the study restrictions.

Exclusion Criteria

• Co-infection with HCV, HIV, HDV, HEV.
• Immune-compromised (known or expected immune deficiency, disease, or use of
medication that may affect the immune system).
• History or other evidence of chronic airway or cardiac disease.
• History of a severe seizure disorder or current anticonvulsant use and
clinically unstable disease.
• Unstable ongoing severe psychiatric disease, especially depression (stable
patients can be included).
• Evidence of an active or suspected cancer or a history of malignancy where
the risk of recurrence is >20% within 5 years.
• Current chronic, acute , or recurrent bacterial, fungal, or viral infection
that is - in the opinion of the treating MD- serious and requires systemic
therapy (within 30 days prior to screening).
• Major organ transplantation.
• Previously received any systemic anti-viral, anti-neoplastic,
immunosuppressive or immuno-modulatory treatment other than Tamiflu, acyclovir
for herpetic lesions or NUC (including supraphysiologic doses of steroids or
radiation) within 3 months prior to inclusion or the expectation that such
treatment will be needed at any time during the study.
• History of HDV, HAV, HIV. Determined as positive within 12 months before
start of study for anti-HDV, anti-HAV IgM, anti-HIV.
• Patients who are expected to need systemic antiviral therapy other than that
provided by the study or Tamiflu at any time during their participation in the
study. Exception: patients who have had a limited (<7 day) course of acyclovir
for herpetic lesions more than 1 month prior to inclusion are not excluded.
• Evidence of liver cirrhosis (Child Pugh A-B-C).
• Serum total bilirubin > 2xULN at screening.
• History or other evidence of bleeding from oesophageal varices or other
conditions consistent with decompensated liver disease.
• History or other evidence of a medical condition associated with chronic
liver disease other than HBV (e.g., hemochromatosis, autoimmune hepatitis,
metabolic liver diseases including Wilson's disease and alfa1-antitrypsin
deficiency, alcoholic liver disease, toxin exposures, thalassemia).
• Hepatic steatosis on ultrasound in the absence of conditions mentioned above
and in the absence of liver fibrosis (histology or fibroscan F0-F1) and with
elevated serum ALT.
• Women with ongoing pregnancy or who are breast feeding.
• Neutrophil count <1.500 cells/mm3 or platelet count <80.000 cells/mm3 at
screening.
• Hemoglobin <7.1 mmol/L (<11.5 g/dL) for females and <7.8 mmol/L (<12.5 g/dL)
for men at screening.
• Serum creatinine level >1.5xULN at screening.
• Patients with a value of alfa-fetoprotein >2xULN, unless stability (less than
10% increase) has been documented over at least the previous 3 months.
• Evidence of current hard drug(s) use and/or alcohol abuse (>20g/day for women
and >30g/day for men)
• No other routine vaccination, nor booster vaccination, within 14 days before
any treatment day or 14 days after a treatment day.
• Participation in an investigational drug, vaccine or device study* within 3
months prior to screening or more than 4 times a year.*Excluding studies
comprising donation of body materials for biobanking or research only.
• Documented allergy to the vaccine or one of its components.
• History or other evidence of severe illness or any other conditions

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Safety:<br /><br>Safety assessments will be performed as specified in the Schedule of<br /><br>Assessments (Table 1, page ..), and will include monitoring and recording of<br /><br>AEs, including SAEs; measurement of protocol specified laboratory assessments<br /><br>and vital signs; and other protocol-specified tests that are deemed critical<br /><br>for the safety evaluation of the study. NCI-CTCAE version 5.0 will be used.</p><br>

Secondary Outcome Measures