Safety Study of Hepatitis E Vaccine (HEV239)
Condition: Hepatitis E; Immunisation
MeSH terms: Hepatitis A; Hepatitis E; Hepatitis
Intervention: HEV 239; Placebo
Intervention description: Hepatitis E vaccine against HEV genotypes 1 and 4. The HEV 239 vaccine is a 26 kDa recombinant polypeptide corresponding to amino acid residues 368-606 of the capsid protein of a genotype 1 HEV strain. The vaccine is expressed in Escherichia coli (E. coli) and vaccine doses contain 30 µg of the purified antigen in 0.5 mL buffered saline adsorbed to 0.8 mg aluminium hydroxide.; 0.9% Sodium Chloride Injection, USP (Normal Saline) is a sterile, nonpyrogenic, isotonic solution of sodium chloride and water for injection (WFI). Each mL contains sodium chloride 9 mg and may contain HCl or NaOH for pH adjustment (pH 5.3 [4.5 - 7.0]).
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Adult; Healthy; Hecolin; Hepatitis E; HEV239; Immunogenicity; Placebo; Population; Reactogenicity; Route; Safety; Vaccine

Summary:

      This is a Phase I double-blind, randomized, placebo controlled trial (1:4 ratio of placebo to
      vaccine) of Hepatitis E virus vaccine containing a 239 amino acid subfragment of Hecolin(R)
      (HEV-239) in 25 US males and non-pregnant females ages 18 - 45 (inclusive) to assess the
      safety, reactogenicity, and immunogenicity of HEV-239. Subjects will receive 3 doses of study
      product on Days 1, 29, and 180. Subjects will remain in the study for up to 13 months
      (including screening). The study duration will be approximately 15 months. Subjects will be
      observed for 30 minutes after vaccination. The occurrence of solicited injection site and
      systemic reactogenicity events will be measured from the time of study vaccination through
      Day 8 after each vaccination. These will be ascertained through use of an electronic memory
      (e-memory) aid, a telephone call on day 4 after each dose of vaccine, a Day 8 clinic visit,
      and potentially at the Day 15 clinic visit after each dose of vaccine. Unsolicited adverse
      events will be collected from vaccination through Day 29 after each vaccination. Serious
      adverse events will be collected from the time of the first study vaccination through the
      last study visit (Day 360). The study includes multiple phlebotomy time points for
      immunogenicity and blood collection for future use at visit 1 and Days 8, 15, and 29 after
      each vaccination. The durability of the immune response and future use collection will be
      assessed at 5 months after the first boost (Day 180) and at 6 months after the second boost
      (Day 360). The primary objectives of the study are to; 1) assess the safety and
      reactogenicity of HEV-239 following delivery of each vaccine dose; and 2) assess the number
      of subjects with > / = 4 fold rise in Hepatitis E virus (HEV) immunoglobulin G (IgG) at any
      time after vaccination.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subject must provide written informed consent.

          2. Subject must be able to comprehend and willing to comply with all study visits and
             procedures (up to 13 months from enrollment).

          3. Subject must be a man or a non-pregnant woman* aged 18-45 years (inclusive).

             *Females of childbearing potential must have a negative serum human chorionic
             gonadotropin (beta-HCG) pregnancy test at screening and negative urine beta-HCG
             pregnancy test within 24 hours prior to (each) vaccination.

          4. Subject must be in good general health as determined by medical history, vital signs*,
             body mass index (BMI)**, physical examination, and clinical judgment of the
             investigator.

             *Oral temp < 38.0 Degrees Celsius /100.4 Degrees Fahrenheit; pulse 51 to 100 bpm;
             systolic blood pressure 90 to 140 mm Hg, and diastolic blood pressure 55 to 90 mm Hg.

             **BMI > / = 18.5 and < 35 kg/m^2.

          5. Subject's screening laboratory values*,** must be within site normal limits*** within
             28 days of enrollment.

             *Screening labs will include: White blood cell (WBC) count; Hemoglobin (HgB);
             Platelets; Absolute neutrophil count (ANC); Absolute eosinophil count (AEC);
             Creatinine; Glucose (random, must be < 140); Alanine Aminotransferase (ALT); HIV 1/2
             antibody/antigen test, Hepatitis B surface antigen (HBsAg), and Hepatitis C virus
             (HCV) antibody.

             **Minor abnormalities are considered acceptable if not clinically significant (e.g.,
             Mean Corpuscular Volume (MCV)). Repeating the screening tests once is permitted for
             out-of-range values provided there is an alternative explanation for the out-of-range
             value. The alternative explanation for the out-of-range value should be documented in
             the subject's source documents.

             ***Creatinine, glucose, and ALT values lower than the normal range may be acceptable
             if the PI or a designated licensed clinician determines that these laboratory findings
             are not clinically significant. The HIV 1/2 antibody/antigen test, Hepatitis B surface
             antigen (HBsAg), and Hepatitis C virus (HCV) antibody must be non-reactive.

          6. Subject's Hepatitis E Virus (HEV) - specific Immunoglobulin G (IgG) and Immunoglobulin
             M (IgM) are negative by ELISA at screening.

          7. Subject agrees to not to participate in another clinical trial during the study
             period.

          8. Subject agrees not to donate blood from screening through Day 270.

          9. Female subjects must be of non-childbearing potential* OR must use an acceptable
             method of contraception** from 28 days before prime vaccination until at least 3
             months after the last vaccination.

             *Surgically sterile via tubal ligation, bilateral oophorectomy, hysterectomy or
             postmenopausal for > / = 1 year.

             **Abstinence (defined as refraining from heterosexual intercourse), monogamous
             relationship with vasectomized partner, barrier methods such as male or female condoms
             with spermicide or diaphragms with spermicide, intrauterine devices, and licensed
             hormonal methods (such as birth control pills, skin patches, Implanon(R),
             Nexplanon(R), DepoProvera(R), or NuvaRing(R)).

         10. Male subjects must be surgically sterile via vasectomy OR must use an acceptable
             method of contraception* from prime vaccination until at least 3 months after the last
             boost vaccination.

               -  Abstinence (defined as refraining from heterosexual intercourse), or condoms with
                  spermicide.

         11. Subjects must have consistent access to the internet to perform electronic data entry.

        Exclusion Criteria:

          1. Has a previous HEV infection or chronic liver disease.

          2. Has received any experimental agent* within 30 days prior to first vaccination, or the
             expected recipient of any experimental agent during this trial-reporting period.

             *Including vaccines, drugs, biologics, devices, and/or blood products.

          3. Female subject is pregnant (or has a positive pregnancy test prior to vaccination) or
             breast feeding, or planning to become pregnant within 3 months after the last boost
             vaccination.

          4. Fever (> / = 38.0 Degrees Celsius / 100.4 Degrees Fahrenheit) or other acute illness
             within 3 days prior to first vaccination.

          5. Infection requiring systemic antibiotics or antiviral treatment within the 7 days
             prior to first vaccination.

          6. Has a positive urine drug screen for amphetamines*, cocaine, opiates, or
             phencyclidine.

             *Prescription amphetamines are not exclusionary.

          7. Chronic, clinically significant medical or psychiatric conditions* that, in the
             opinion of the investigator, may pose additional risk to the subject if she/he
             participates in the study.

             *Permissible conditions include but are not limited to mild, well-controlled asthma,
             well-controlled depression, well-controlled anxiety, seasonal allergies, and
             well-controlled hypertension.

          8. Receipt of immunosuppressive drugs*,**,*** or biologic agents within the 30 days prior
             to enrollment.

             *This includes use of oral or parental prednisone. This also includes allergy
             desensitization injections from 14 days prior to each vaccination through 14 days
             after each vaccination. The use of topical steroids for mild uncomplicated dermatitis
             permissible after therapy is completed. Over-the-counter (OTC) corticosteroid nasal
             sprays for allergic rhinitis are permissible. The use of low or moderate dose inhaled
             steroids is permissible. Doses are defined as per age as using inhaled high-dose per
             reference chart in the National Heart, Lung and Blood Institute Guidelines for the
             Diagnosis and Management of Asthma (EPR-3) or other lists published in UPTODATE.

             **Receipt of systemic, prescription medications for the treatment of chronic medical
             conditions or variations of normal physiologic functions may be permissible if, in the
             opinion of the investigator, they are used for conditions that are not clinically
             significant and would not impact the safety of the subject or the safety and
             immunogenicity outcomes of the protocol.

             ***Use of systemic, over-the-counter medications and PRN systemic, prescription
             medication may be allowed if, in the opinion of the investigator, they pose no
             additional risk to subject safety or assessment of immunogenicity/reactogenicity.

          9. Has known neoplastic disease* anticancer therapy, or radiation therapy within 3 years
             prior to first study vaccination.

             *Excluding non-melanoma skin cancer, such as squamous cell skin cancer or basal cell
             skin cancer, cured by surgical excision.

         10. Has a history of any hematologic malignancy at any time.

         11. Has a known or suspected congenital or acquired disease that impairs the immune
             system, including functional asplenia or immunosuppression as a result of underlying
             illness or treatment.

         12. Has prior organ and/or stem cell transplant.

         13. Has a history of abuse of alcohol or drugs that, in the opinion of the investigator,
             may interfere with the subject's ability to comply with the protocol.

         14. Has behavioral or cognitive impairment or psychiatric conditions that, in the opinion
             of the investigator, may interfere with the subject's ability to participate in the
             trial.

         15. Has received blood products or immunoglobulin within six months prior to vaccination.

         16. Travel to Asia, the Middle East, Africa, or Central America or to an area with an
             active Hepatitis E outbreak* within the last 90 days or intention to travel to such
             areas during the study.

             *Outbreaks within the last 3 years.

         17. Receipt of any inactivated vaccine from 2 weeks prior to each vaccination through 2
             weeks after each vaccination.

         18. Receipt of any live vaccine from 4 weeks prior to each vaccination through 4 weeks
             after each vaccination.

         19. Known hypersensitivity or allergy to aluminum, any component of the vaccine, or other
             serious adverse reactions to vaccines or vaccine products.

         20. Subject who, in the opinion of the investigator, is unlikely to adhere to the
             requirements of the study.

         21. Any condition that, in the opinion of the investigator, might interfere with assessing
             the study objectives.