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

Hepatitis B Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02496897
• Other study ID #: FP02.2_CS_01
• Status: Completed
• Phase: Phase 1
• Start date: July 2015
• Est. completion date: June 5, 2018

Study information

• Verified date: March 2018
• Source: Altimmune, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: June 5, 2018
• Est. primary completion date: October 13, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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 menstral 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.

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B

Intervention

Biological:
• FP-02.2 Vaccine
Synthetic Peptide Hepatitis B Vaccine

Other:
• Placebo
Placebo
• IC31® Adjuvant
IC31® Adjuvant

Locations

Country	Name	City	State
Korea, Republic of	Pusan National University Busan Hospital	Busan
Korea, Republic of	Keimyung University Dongsan Medical Center	Daegu
Korea, Republic of	Kyungpook National University Hospital	Daegu
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Korea University Guro Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Seoul St. Mary's Hospital	Seoul
Korea, Republic of	SMG-SNU Boramae Medical Center	Seoul
Korea, Republic of	Yonsei University Health System Severance Hospital	Seoul
Korea, Republic of	Pusan National University Yangsan Hospital	Yangsan
United Kingdom	University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital	Birmingham
United Kingdom	University Hospitals Bristol	Bristol
United Kingdom	Barts and The London School of Medicine and Dentistry, Blizzard Institiue	London
United Kingdom	Imperial College London - St Mary's Campus	London
United Kingdom	King's College Hospital	London
United Kingdom	Royal Free Hospital	London
United Kingdom	St. George's Hospital and Medical School	London
United Kingdom	Pennine Acute Hospitals	Manchester
United Kingdom	Bradford Teaching Hospitals, Bradford Royal Infirmary	North Yorkshire
United Kingdom	Queen's Medical Centre, Nottingham Hospital	Nottingham

Sponsors (1)

Lead Sponsor	Collaborator
Altimmune, Inc.

Countries where clinical trial is conducted

Korea, Republic of,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety Adverse Events and Clinical Laboratory Abnormalities	Adverse Events and Clinical Laboratory Abnormalities	Throughout the study to day 85
Secondary	Immunological Response	IFN-gamma ELISpot assay specific for FP-02.2 peptides using cryopreserved PBMCs	Throughout the study to day 85