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Safety Study of Hepatitis E Vaccine (HEV239)

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ClinicalTrials.gov Identifier: NCT03827395
Recruitment Status : Recruiting
First Posted : February 1, 2019
Last Update Posted : May 8, 2020
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Tracking Information
First Submitted Date  ICMJE January 31, 2019
First Posted Date  ICMJE February 1, 2019
Last Update Posted Date May 8, 2020
Actual Study Start Date  ICMJE April 11, 2019
Estimated Primary Completion Date April 30, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 31, 2019)
  • Number of clinical safety laboratory adverse events (AE) [ Time Frame: Day 188 ]
  • Number of clinical safety laboratory adverse events (AE) [ Time Frame: Day 37 ]
  • Number of clinical safety laboratory adverse events (AE) [ Time Frame: Day 9 ]
  • Number of solicited local reactogenicity events [ Time Frame: From Day 1 through Day 9 ]
  • Number of solicited local reactogenicity events [ Time Frame: From Day 180 through Day 188 ]
  • Number of solicited local reactogenicity events [ Time Frame: From Day 29 through Day 37 ]
  • Number of solicited systemic reactogenicity events [ Time Frame: From Day 1 through Day 9 ]
  • Number of solicited systemic reactogenicity events [ Time Frame: From Day 180 through Day 188 ]
  • Number of solicited systemic reactogenicity events [ Time Frame: From Day 29 through Day 37 ]
  • Number of subjects showing > / = 4 fold rise in serum HEV IgG concentration by ELISA from the baseline [ Time Frame: Day 15 ]
  • Number of subjects showing > / = 4 fold rise in serum HEV IgG concentration by ELISA from the baseline [ Time Frame: Day 187 ]
  • Number of subjects showing > / = 4 fold rise in serum HEV IgG concentration by ELISA from the baseline [ Time Frame: Day 194 ]
  • Number of subjects showing > / = 4 fold rise in serum HEV IgG concentration by ELISA from the baseline [ Time Frame: Day 208 ]
  • Number of subjects showing > / = 4 fold rise in serum HEV IgG concentration by ELISA from the baseline [ Time Frame: Day 29 ]
  • Number of subjects showing > / = 4 fold rise in serum HEV IgG concentration by ELISA from the baseline [ Time Frame: Day 36 ]
  • Number of subjects showing > / = 4 fold rise in serum HEV IgG concentration by ELISA from the baseline [ Time Frame: Day 360 ]
  • Number of subjects showing > / = 4 fold rise in serum HEV IgG concentration by ELISA from the baseline [ Time Frame: Day 43 ]
  • Number of subjects showing > / = 4 fold rise in serum HEV IgG concentration by ELISA from the baseline [ Time Frame: Day 57 ]
  • Number of subjects showing > / = 4 fold rise in serum HEV IgG concentration by ELISA from the baseline [ Time Frame: Day 8 ]
  • Number of vaccine-related serious adverse events (SAE) [ Time Frame: Day 1 through Day 360 ]
  • Number of vaccine-related unsolicited adverse events (AE) [ Time Frame: From Day 1 through Day 30 ]
  • Number of vaccine-related unsolicited adverse events (AE) [ Time Frame: From Day 180 through Day 209 ]
  • Number of vaccine-related unsolicited adverse events (AE) [ Time Frame: From Day 29 through Day 58 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 31, 2019)
  • HEV IgG Geometric Mean Concentrations (GMCs) by ELISA [ Time Frame: Day 1 ]
  • HEV IgG Geometric Mean Concentrations (GMCs) by ELISA [ Time Frame: Day 15 ]
  • HEV IgG Geometric Mean Concentrations (GMCs) by ELISA [ Time Frame: Day 180 ]
  • HEV IgG Geometric Mean Concentrations (GMCs) by ELISA [ Time Frame: Day 187 ]
  • HEV IgG Geometric Mean Concentrations (GMCs) by ELISA [ Time Frame: Day 194 ]
  • HEV IgG Geometric Mean Concentrations (GMCs) by ELISA [ Time Frame: Day 208 ]
  • HEV IgG Geometric Mean Concentrations (GMCs) by ELISA [ Time Frame: Day 29 ]
  • HEV IgG Geometric Mean Concentrations (GMCs) by ELISA [ Time Frame: Day 36 ]
  • HEV IgG Geometric Mean Concentrations (GMCs) by ELISA [ Time Frame: Day 360 ]
  • HEV IgG Geometric Mean Concentrations (GMCs) by ELISA [ Time Frame: Day 43 ]
  • HEV IgG Geometric Mean Concentrations (GMCs) by ELISA [ Time Frame: Day 57 ]
  • HEV IgG Geometric Mean Concentrations (GMCs) by ELISA [ Time Frame: Day 8 ]
  • Number of subjects with HEV IgG seroconversion by ELISA [ Time Frame: Day 15 ]
  • Number of subjects with HEV IgG seroconversion by ELISA [ Time Frame: Day 180 ]
  • Number of subjects with HEV IgG seroconversion by ELISA [ Time Frame: Day 187 ]
  • Number of subjects with HEV IgG seroconversion by ELISA [ Time Frame: Day 194 ]
  • Number of subjects with HEV IgG seroconversion by ELISA [ Time Frame: Day 208 ]
  • Number of subjects with HEV IgG seroconversion by ELISA [ Time Frame: Day 29 ]
  • Number of subjects with HEV IgG seroconversion by ELISA [ Time Frame: Day 36 ]
  • Number of subjects with HEV IgG seroconversion by ELISA [ Time Frame: Day 360 ]
  • Number of subjects with HEV IgG seroconversion by ELISA [ Time Frame: Day 43 ]
  • Number of subjects with HEV IgG seroconversion by ELISA [ Time Frame: Day 57 ]
  • Number of subjects with HEV IgG seroconversion by ELISA [ Time Frame: Day 8 ]
  • Number of subjects with HEV IgM seroconversion by ELISA [ Time Frame: Day 15 ]
  • Number of subjects with HEV IgM seroconversion by ELISA [ Time Frame: Day 180 ]
  • Number of subjects with HEV IgM seroconversion by ELISA [ Time Frame: Day 187 ]
  • Number of subjects with HEV IgM seroconversion by ELISA [ Time Frame: Day 194 ]
  • Number of subjects with HEV IgM seroconversion by ELISA [ Time Frame: Day 208 ]
  • Number of subjects with HEV IgM seroconversion by ELISA [ Time Frame: Day 29 ]
  • Number of subjects with HEV IgM seroconversion by ELISA [ Time Frame: Day 36 ]
  • Number of subjects with HEV IgM seroconversion by ELISA [ Time Frame: Day 360 ]
  • Number of subjects with HEV IgM seroconversion by ELISA [ Time Frame: Day 43 ]
  • Number of subjects with HEV IgM seroconversion by ELISA [ Time Frame: Day 57 ]
  • Number of subjects with HEV IgM seroconversion by ELISA [ Time Frame: Day 8 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety Study of Hepatitis E Vaccine (HEV239)
Official Title  ICMJE A Phase 1, Double-Blinded, Placebo Controlled, Clinical Trial to Evaluate the Safety, Reactogenicity, and Immunogenicity of HEV-239 (Hecolin(R)) in a Healthy US Adult Population
Brief 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.
Detailed Description 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. The secondary objectives are to; 1) Assess the number of subjects with HEV immunoglobulin M (IgM) seroconversion at any time after vaccination; 2) Assess the number of subjects with HEV IgG seroconversion at any time after vaccination; and 3) Assess the HEV IgG geometric mean concentrations (GMCs) at any time after vaccination.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Condition  ICMJE
  • Hepatitis E
  • Immunisation
Intervention  ICMJE
  • Biological: HEV 239
    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.
  • Other: Placebo
    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]).
Study Arms  ICMJE
  • Experimental: HEV-239
    0.5 mL of HEV-239 administered intramuscularly into the deltoid muscle as a single injection on Days 1, 29, and 180. N=20
    Intervention: Biological: HEV 239
  • Placebo Comparator: Placebo
    0.5 mL of HEV-239 placebo administered intramuscularly into the deltoid muscle as a single injection on Days 1, 29, and 180. N=5
    Intervention: Other: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 31, 2019)
25
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 30, 2020
Estimated Primary Completion Date April 30, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Evan Anderson 14047129033 evanderson@emory.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03827395
Other Study ID Numbers  ICMJE 15-0108
HHSN272201300018I
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Institute of Allergy and Infectious Diseases (NIAID)
Study Sponsor  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account National Institute of Allergy and Infectious Diseases (NIAID)
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP