Phase I Safety and Immunogenicity of FP-02.2 in Chronic Hepatitis B

A Phase I, Randomized, Double-blind, Placebo-controlled, Multi-centre, Ascending-dose Trial to Evaluate the Safety, Tolerability and Immunogenicity of Vaccine FP-02.2 in HBeAg-negative Hepatitis B Patients as an add-on Treatment to Entecavir or Tenofovir.

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.

Study Overview

• Status: Completed
• Conditions: Hepatitis B
• Intervention / Treatment: Other: Placebo; Biological: FP-02.2 Vaccine; Other: IC31® Adjuvant

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.

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Busan, Korea, Republic of, 49241
    • Pusan National University Busan Hospital
  • Daegu, Korea, Republic of, 41944
    • Kyungpook National University Hospital
  • Daegu, Korea, Republic of, 41931
    • Keimyung University Dongsan Medical Center
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 03722
    • Yonsei University Health System Severance Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 07061
    • SMG-SNU Boramae Medical Center
  • Seoul, Korea, Republic of, 06591
    • Seoul St. Mary'S Hospital
  • Seoul, Korea, Republic of, 152703
    • Korea University Guro Hospital
  • Yangsan, Korea, Republic of, 50612
    • Pusan National University Yangsan Hospital
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital
  • Bristol, United Kingdom, BS1 3NU
    • University Hospitals Bristol
  • London, United Kingdom, Nw3 2QG
    • Royal Free Hospital
  • London, United Kingdom, SW17 0QT
    • St. George's Hospital and Medical School
  • London, United Kingdom, E1 2AT
    • Barts and The London School of Medicine and Dentistry, Blizzard Institiue
  • London, United Kingdom, E1 2AT
    • King's College Hospital
  • London, United Kingdom, W2 1NY
    • Imperial College London - St Mary's Campus
  • Manchester, United Kingdom, M8 5RB
    • Pennine Acute Hospitals
  • North Yorkshire, United Kingdom, BD9 6RJ
    • Bradford Teaching Hospitals, Bradford Royal Infirmary
  • Nottingham, United Kingdom, NG7 2UH
    • Queen's Medical Centre, Nottingham Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Biological: FP-02.2 Vaccine; Synthetic Peptide Hepatitis B Vaccine
Experimental: 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.	Biological: FP-02.2 Vaccine; Synthetic Peptide Hepatitis B Vaccine
Experimental: 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.	Biological: FP-02.2 Vaccine; Synthetic Peptide Hepatitis B Vaccine; Other: IC31® Adjuvant; IC31® Adjuvant
Experimental: 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.	Biological: FP-02.2 Vaccine; Synthetic Peptide Hepatitis B Vaccine; Other: IC31® Adjuvant; IC31® Adjuvant
Placebo Comparator: Placebo; Placebo administered by IM injection on Days 1, 29, and 57.	Other: Placebo; Placebo
Experimental: IC31® Adjuvant; IC31® Adjuvant alone administered by IM injection on Days 1, 29, and 57.	Other: IC31® Adjuvant; IC31® Adjuvant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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,	Throughout the study to Day 85
Number of Subjects With Local Injection Site Reactions	Incidence of local injection site reactions occurring up to 7 days after each injection	Days 1 through 64

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunological Response	IFN-gamma ELISpot assay specific for FP-02.2 peptides using cryopreserved PBMCs	Change from baseline to Day 85

Collaborators and Investigators

• Sponsor: Altimmune, Inc.
• Investigators: Principal Investigator: Mark Thursz, MD, Imperial College London

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2015
• Primary Completion (Actual): October 13, 2017
• Study Completion (Actual): June 5, 2018

Study Registration Dates

• First Submitted: July 6, 2015
• First Submitted That Met QC Criteria: July 13, 2015
• First Posted (Estimated): July 14, 2015

Study Record Updates

• Last Update Posted (Actual): May 22, 2025
• Last Update Submitted That Met QC Criteria: May 21, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Blood-Borne Infections; Infections; RNA Virus Infections; Virus Diseases; Digestive System Diseases; Liver Diseases; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Communicable Diseases; DNA Virus Infections; Hepadnaviridae Infections; Hepatitis A; Hepatitis; Hepatitis B
• Other Study ID Numbers: FP02.2_CS_01