Efficacy and Immunogenicity of Norovirus GI.1/GII.4 Bivalent Virus-like Particle Vaccine in Adults

Phase 2b, Double-Blind, Randomized, Placebo-Controlled Trial to Evaluate the Efficacy and Immunogenicity of the Intramuscular Norovirus GI.1/GII.4 Bivalent Virus-like Particle Vaccine in Healthy Adults Aged 18 - 49 Years

The purpose of this study is to evaluate the efficacy of the Norovirus (NoV) GI.1/GII.4 bivalent virus-like particle vaccine against moderate or severe acute gastroenteritis (AGE) due to genotype-specific (GI.1 and GII.4) NoV strains.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Biological: NoV Placebo-matching Saline; Biological: NoV GI.1/GII.4 Bivalent VLP Vaccine

Detailed Description

The vaccine being tested in this study is called NoV GI.1/GII.4 bivalent VLP vaccine adjuvanted with aluminum hydroxide. The norovirus vaccine is being tested to prevent AGE due to genotype-specific (GI.1 and GII.4) norovirus strains in healthy participants recruited from a US military training installation. This study will look at the illness rate of AGE occurring > 7 days after dosing due to genotype-specific (GI.1 or GII.4) NoV strains represented in the vaccine.

The study will enroll between 2800 and 8700 patients. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups-which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):

• Norovirus GI.1/GII.4 Bivalent VLP Vaccine
• Placebo (dummy inactive solution) - this is a liquid that looks similar to the study drug but has no active ingredient

All participants will receive one dose of study medication on Day 1 administered via intramuscular injection.

This multi-center trial will be conducted in the United States at select military locations. The overall time to participate in this study is up to 45 days for participants in the navy 53 days for participants in the Air Force, and 72 days for participants in the marines. Participants will make multiple visits to the clinic, including a final visit on the last day of study participation (Day 45, 53 or 72) for a follow-up assessment.

• Study Type: Interventional
• Enrollment (Actual): 4748
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Great Lakes, Illinois, United States, 60088
      • Great Lakes Naval Station

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 49 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Participant 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.
2. Male or female participants, 18 to 49 years of age.
3. Is in good health at the time of entry into the trial as determined by medical history and the clinical judgment of the investigator.
4. Can comply with trial procedures and are available for the duration of follow-up.

Exclusion Criteria:

1. Pregnancy.
2. Has known hypersensitivity to any of the Norovirus (NoV) GI.1/GII.4 bivalent virus-like particle (VLP) vaccine components (including excipients).
3. Has known hypersensitivity or allergy to any of the licensed required concomitant vaccine components to be administered (including excipients of these vaccines).
4. Has any condition or circumstance that the investigator determines would interfere with trial evaluation or interpretation.
5. Has known or suspected impairment or alteration of immune function.
6. Has a history of acute gastroenteritis (AGE) within 14 days of enrollment.
7. Has a history of body temperature of 38.0°C (100.4°F) or higher within 3 days of intended trial vaccination.
8. Has received blood, blood products, and/or plasma derivatives or any parenteral immunoglobulin antibody preparation in the past 3 months.
9. Immunosuppressive therapy within 3 months or systemic (e.g., oral or parenteral) corticosteroid treatment within 60 days prior to investigational trial dose administration.
10. Is participating in any clinical trial with another investigational product 30 days prior to the first trial visit or intending to participate in another clinical trial at any time during the conduct of this trial.
11. Participants who are first-degree relatives of individuals involved in the conduct of the trial.
12. Has any history of progressive or severe neurologic disorder, seizure disorder or neuro-inflammatory disease (e.g. Guillain-Barré syndrome).
13. 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.
14. Has received any other vaccines within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to enrollment in this trial with the exception of routine immunizations as per Military Procedures.

15. 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:

       • Hormonal contraceptive (such as oral, injection, transdermal patch, implant, cervical ring).
       • Barrier (condom with spermicide or diaphragm with spermicide) each and every time during intercourse.
       • Intrauterine device (IUD).
       • Monogamous relationship with vasectomized partner. Partner must have been vasectomized for at least six months prior to the participants' trial entry.
16. If female of childbearing potential and sexually active, refusal to use an "acceptable contraceptive method" from Day 1 through 6 months after the last dose of trial vaccine. In addition, they must be advised not to donate ova during this period.
17. Has any positive or indeterminate pregnancy test.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; NoV placebo-matching 0.5 mL solution for injection, intramuscularly (IM), once, on Day 1.	Biological: NoV Placebo-matching Saline; NoV placebo-matching saline (0.9% sodium chloride).
Experimental: NoV GI.1/GII.4 Bivalent VLP Vaccine; NoV GI.1/GII.4 bivalent virus-like particle (VLP) vaccine, 0.5 mL injection, intramuscularly (IM), once, on Day 1.	Biological: NoV GI.1/GII.4 Bivalent VLP Vaccine; NoV bivalent VLP vaccine, adjuvanted with 500 µg aluminum as Al(OH)3.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Moderate or Severe Acute Gastroenteritis (AGE) Occurring for >7 Days After Dosing Due to GI.1 or GII.4 Norovirus Strains (Excluding Co-infection)	Acute gastroenteritis (AGE) is a sudden inflammation or swelling in the lining of the stomach causing diarrhea and vomiting. A norovirus AGE case was defined as meeting the work-up definition plus a norovirus positive stool sample or vomitus sample confirmed by reverse transcriptase polymerase chain reaction (RT-PCR). The severity of AGE was graded by the investigator as per CTCAE criteria. AGE occurring due to NoV strains excluding co-infection with Salmonella, Shigella or Campylobacter is reported. The Norovirus strains included: GI.1, GI.7a, GII.2 and GII.4.	Up to Day 47

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Moderate or Severe AGE Occurring >7 Days After Dosing Due to Any Norovirus Strain (Excluding Co-infection)	Acute gastroenteritis (AGE) is a sudden inflammation or swelling in the lining of the stomach causing diarrhea and vomiting. A norovirus AGE case was defined as meeting the work-up definition plus a norovirus positive stool sample or vomitus sample confirmed by RT-PCR. The severity of AGE was graded by the investigator as per CTCAE criteria. AGE occurring due to NoV strains excluding co-infection with Salmonella, Shigella or Campylobacter is reported. The Norovirus strains included: GI.1, GI.7a, GII.2 and GII.4.	Up to Day 47
Number of Participants With Moderate or Severe AGE Occurring >7 Days After Dosing Due to Any Norovirus Strain (Including Co-infection)	Acute gastroenteritis (AGE) is a sudden inflammation or swelling in the lining of the stomach causing diarrhea and vomiting. A norovirus AGE case was defined as meeting the work-up definition plus a norovirus positive stool sample or vomitus sample confirmed by RT-PCR. The severity of AGE was graded by the investigator as per CTCAE criteria. AGE occurring due to NoV strains including co-infection with Salmonella, Shigella or Campylobacter is reported. The Norovirus strains included: GI.1, GI.7a, GII.2 and GII.4.	Up to Day 47
Number of Participants With Moderate or Severe AGE Occurring >7 Days After Dosing Due to GI.1 or GII.4 Norovirus Strains (Including Co-infection)	Acute gastroenteritis (AGE) is a sudden inflammation or swelling in the lining of the stomach causing diarrhea and vomiting. A norovirus AGE case was defined as meeting the work-up definition plus a norovirus positive stool sample or vomitus sample confirmed by RT-PCR. The severity of AGE was graded by the investigator as per CTCAE criteria. AGE occurring due to NoV strains including co-infection with Salmonella, Shigella or Campylobacter is reported. The Norovirus strains included: GI.1, GI.7a, GII.2 and GII.4.	Up to Day 47

Collaborators and Investigators

• Sponsor: Takeda

Study record dates

Study Major Dates

• Study Start (Actual): June 14, 2016
• Primary Completion (Actual): June 16, 2018
• Study Completion (Actual): June 16, 2018

Study Registration Dates

• First Submitted: January 27, 2016
• First Submitted That Met QC Criteria: January 27, 2016
• First Posted (Estimate): January 29, 2016

Study Record Updates

• Last Update Posted (Actual): June 10, 2021
• Last Update Submitted That Met QC Criteria: May 14, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Drug therapy
• Other Study ID Numbers: NOR-211; U1111-1175-9077 (Registry Identifier: WHO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No