Clinical trial NCT02475278: Serologic Assay Validation, Proficiency Testing, Safety and Immunogenicity of Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine
Official title: Phase II, Single Arm, Open Label Trial for Serologic Assay Validation, Proficiency Testing, Safety and Immunogenicity of the Intramuscular Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Norovirus
Healthy Participants
Keywords: Drug therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2015-06-18
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: The purpose of this study is to collect serum samples to evaluate serologic assays and to establish proficiency panels for serologic assays used for assessment of post vaccination immune response after intramuscular (IM) vaccination with Norovirus GI.1/GII.4 bivalent virus-like particle (VLP) vaccine.

Detailed description: The vaccine being tested in this study is called Norovirus GI.1/GII.4 bivalent Virus-Like Particle Vaccine (NoV Vaccine). The purpose of this study is to collect serum samples to evaluate serologic assays and to establish proficiency panels for serologic assays used for assessment of post vaccination immune response after intramuscular (IM) vaccination with the NoV vaccine. The validation and proficiency testing of the immunogenicity assays is required to support the NoV Vaccine development program. This study also looked at side effects in people who were administered a single dose of the NoV vaccine.

The study enrolled 50 patients. All participants received one dose of the NoV vaccine via intramuscular injection.

Participants were asked to record any symptoms that may be related to the vaccine or the injection site in a diary card for 7 days after receiving the vaccination.

This single-centre trial was conducted in the United States. The overall time to participate in this study was 183 days. Participants made 4 visits to the clinic, and were contacted by telephone 183 days after last dose of study drug for a follow-up assessment.

Eligibility criteria: Inclusion Criteria:

1. Age 18 to 49 years, inclusive.
2. Is in good health at the time of entry into the trial as determined by medical history, physical examination (including vital signs) and clinical judgment of the investigator.
3. Signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any trial procedures, after the nature of the trial has been explained according to local regulatory requirements.
4. Can comply with trial procedures and are available for the duration of follow-up.
5. Body weight of ≥50kg (110lbs).
6. Body mass index (BMI) \<35.

Exclusion Criteria:

1. Has a history of acute gastroenteritis (AGE) within 14 days of enrollment.
2. Has previously been exposed to an experimental Norovirus (NoV) Vaccine.
3. Has received any inactivated vaccines within 14 days or any live vaccines for 28 days prior to enrollment in this trial or who are planning to receive any vaccine within 28 days of investigational vaccine administration.
4. Has contraindications, warnings and/or precautions to vaccination with the NoV Vaccine as specified within the investigator brochure.
5. Has known hypersensitivity or allergy to any of the NoV Vaccine components (including excipients).
6. Has behavioral or cognitive impairment or psychiatric disease that, in the opinion of the investigator, may interfere with the participant's ability to participate in the trial.
7. Has any history of progressive or severe neurologic disorder, seizure disorder or neuro-inflammatory disease (e.g. Guillain-Barré syndrome).
8. Has history or any illness that, in the opinion of the investigator, might interfere with the results of the trial or pose additional risk to the participants due to participation in the trial.
9. Has known or suspected impairment/alteration of immune function, including:

   1. Chronic use of oral steroids (Equivalent to 20 mg/day prednisone ≥ 12 weeks / ≥ 2 mg/kg body weight / day prednisone ≥ 2 weeks) within 60 days prior to Day 1 (use of inhaled, intranasal, or topical corticosteroids is allowed).
   2. Receipt of parenteral steroids (Equivalent to 20 mg/day prednisone ≥ 12 weeks / ≥ 2 mg/kg body weight / day prednisone ≥ 2 weeks) within 60 days prior to Day 1.
   3. Administration of immunoglobulins and/or any blood products within the three months preceding the first administration of the investigational vaccine or planned administration during the trial (consider whether applicable as an exclusion criterion or criterion for delay).
   4. Receipt of immunostimulants within 60 days prior to Day 1.
   5. Receipt of parenteral, epidural or intra-articular immunoglobulin preparation, blood products, and/or plasma derivates within 3 months prior to Day 1 or planned during the full length of the trial.
   6. Human immunodeficiency virus (HIV) infection or HIV-related disease.
   7. Genetic immunodeficiency.
10. Has abnormalities of splenic or thymic function.
11. Has a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time.
12. Has any serious chronic or progressive disease according to judgment of the investigator (e.g. neoplasm, insulin dependent diabetes, cardiac, renal or hepatic disease).
13. Is participating in any clinical trial with another investigational product 30 days prior to first trial visit or intent to participate in another clinical trial at any time during the conduct of this trial.
14. Is involved in the trial conduct or their first degree relatives.
15. Has history of substance or alcohol abuse within the past 2 years.
16. Females who are pregnant or breastfeeding.
17. If female of childbearing potential, sexually active, and has not used any of the "acceptable contraceptive methods" for at least 2 months prior to trial entry:

    1. Of childbearing potential is defined as status post onset of menarche and not meeting any of the following conditions: menopausal for at least 2 years, status after bilateral tubal ligation for at least 1 year, status after bilateral oophorectomy, or status after hysterectomy.
    2. Acceptable birth control methods are defined as one or more of the following:

    i. Hormonal contraceptive (such as oral, injection, transdermal patch, implant, cervical ring).

    ii. Barrier (condom with spermicide or diaphragm with spermicide) each and every time during intercourse.

    iii. Intrauterine device (IUD). iv. Monogamous relationship with vasectomized partner. Partner must have been vasectomized for at least six months prior to the participants' trial entry.
18. If female of childbearing potential and sexually active, refusal to use an "acceptable contraceptive method" through to 6 months after receipt of investigational vaccine. In addition, they must be advised not to donate ova during this period.
19. Any positive or indeterminate pregnancy test.

Primary outcomes:
measure: Number of Participants With Serum Samples Obtained on Day 8 for Assessment of Seropositivity for Both Anti-NoV GI.1 VLP and GII.4 VLP Antibodies
timeFrame: Day 8
measure: Number of Participants With Serum Samples Obtained on Day 15 for Assessment of Seropositivity for Both Anti-NoV GI.1 VLP and GII.4 VLP Antibodies
timeFrame: Day 15
measure: Number of Participants With Serum Samples Obtained on Day 29 for Assessment of Seropositivity for Both Anti-NoV GI.1 VLP and GII.4 VLP Antibodies
timeFrame: Day 29
Secondary outcomes:
measure: Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) by Maximum Severity
timeFrame: Days 1 through 7
measure: Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Maximum Severity
timeFrame: Days 1 through 7
measure: Percentage of Participants With Elevated Daily Oral Temperature
timeFrame: Days 1 to 7 days after vaccination
measure: Percentage of Participants With Unsolicited Adverse Events (AEs) by Maximum Severity
timeFrame: Days 1 through 28
measure: Percentage of Participants Experiencing Serious Adverse Events
timeFrame: Day 1 up to Day 183
Other outcomes:
Locations:
city: Austin
country: United States
facility: Benchmark Research Austin
state: Texas
Study officials:
affiliation: Takeda
name: Medical Director Clinical Science
role: STUDY_DIRECTOR
References:
citation: Atmar RL, Ettayebi K, Ayyar BV, Neill FH, Braun RP, Ramani S, Estes MK. Comparison of Microneutralization and Histo-Blood Group Antigen-Blocking Assays for Functional Norovirus Antibody Detection. J Infect Dis. 2020 Feb 18;221(5):739-743. doi: 10.1093/infdis/jiz526.
citation: Atmar RL, Cramer JP, Baehner F, Han C, Borkowski A, Mendelman PM. An Exploratory Study of the Salivary Immunoglobulin A Responses to 1 Dose of a Norovirus Virus-Like Particle Candidate Vaccine in Healthy Adults. J Infect Dis. 2019 Jan 9;219(3):410-414. doi: 10.1093/infdis/jiy529.