Long-Term Immunogenicity of the Norovirus GI.1/GII.4 Bivalent Virus-like Particle (VLP) Vaccine (NoV Vaccine) in Adults

A Phase 2, Long-Term Immunogenicity Follow-up Trial of Adult and Elderly Subjects Who Have Previously Received an Intramuscular Injection of Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine

The purpose of this study is to evaluate descriptively the long-term immunogenicity of at least 1 NoV vaccine administration.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers; Norovirus
• Intervention / Treatment: Biological: NoV Vaccine

Detailed Description

Results prepared and posted by Takeda on behalf of Hillevax, the IND holder.

The drug being tested in this study is called NoV vaccine. NoV vaccine is being tested for protection against acute gastroenteritis (AGE) due to norovirus.

The study will enroll maximum of approximately 575 participants. Participants who previously received NoV vaccine in studies NOR-107, NOR-210 and NOR-204 will be enrolled. Participants from study NOR-107 will enter the study at the time of their 3rd year post-primary vaccination, and from studies NOR-210 and NOR-204, at their 2nd year post-primary vaccination. The duration of participation in the study will be different for each participant.

This multi-center trial will be conducted in Belgium and the United States. The overall time to participate in this study is maximum 5 years after primary NoV vaccination. Participants will have a maximum of 4 visits over 3 years

• Study Type: Interventional
• Enrollment (Actual): 528
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Antwerpen, Belgium, 2610
    • Universiteit Antwerpen
  • Gent, Belgium, 9000
    • Universitair Ziekenhuis Gent
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35211
      • Simon-Williamson Clinic/Synexus Clinical Research US, Inc
  • Arizona
    • Fountain Hills, Arizona, United States, 85268
      • Synexus Clinical Research US, Inc./Fountain Hills Family Practice, P.C.
  • Colorado
    • Littleton, Colorado, United States, 80127
      • Synexus Clinical Research US, Inc/Southwest Family Medicine
  • Florida
    • Miami, Florida, United States, 33143
      • Miami Research Associates
  • Kansas
    • Lenexa, Kansas, United States, 66219
      • Johnson County Clin-Trials
  • Missouri
    • Saint Louis, Missouri, United States, 63106
      • St. Louis University, School of Medicine
  • New York
    • Endwell, New York, United States, 13760
      • Regional Clinical Research Inc.
    • Rochester, New York, United States, 14642
      • University of Rochester
  • Texas
    • Austin, Texas, United States, 78705
      • Benchmark Research Austin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male and female participants who previously received at least 1 dose of NoV vaccine in trials NOR-107 (NCT02038907), NOR-210 (NCT02475278) and NOR-204 (NCT02661490), have baseline and post-vaccination data, and completed the primary vaccination trial protocol as initially described.

Exclusion Criteria:

1. Participation in any clinical trial is allowed, on condition that no investigational product is administered within 30 days prior to blood sampling.
2. In the opinion of the investigator, the participant is not medically eligible to provide blood specimens.
3. Individuals with 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

20

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NOR-107: GI.1/GII.4 (15/15/500) μg- MPL 50 μg,1-Dose; Eligible participants who received Hepatitis A vaccine, intramuscular (IM), on Day 1, followed by norovirus bivalent virus like particle (VLP) vaccine (15 µg of GI.1 norovirus virus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 50 µg monophosphoryl lipid A (MLP) and 500 µg aluminium hydroxide, IM on Day 28 in previous study NOR-107 were enrolled at 3rd year post-primary vaccination in this study.	Biological: NoV Vaccine; NoV vaccine injection administered.
Experimental: NOR-107: GI.1/GII.4 (15/50/500) μg- MPL 50 μg,1-Dose; Eligible NOR-107 participants who had received Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MPL and 500 µg aluminium hydroxide, on Day 28 were enrolled at 3rd year post-primary vaccination in NOR-213 study.	Biological: NoV Vaccine; NoV vaccine injection administered.
Experimental: NOR-107: GI.1/GII.4 (50/50/500) μg- MPL 50 μg,1-Dose; Eligible NOR-107 participants who had received Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (50 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MPL and 500 µg aluminium hydroxide, on Day 28 were enrolled at 3rd year post-primary vaccination in NOR-213 study.	Biological: NoV Vaccine; NoV vaccine injection administered.
Experimental: NOR-107: GI.1/GII.4 (15/15/500) μg- MPL 15 μg,1-Dose; Eligible NOR-107 participants who had received Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 15 µg MPL and 500 µg aluminium hydroxide, on Day 28 were enrolled at 3rd year post-primary vaccination in NOR-213 study.	Biological: NoV Vaccine; NoV vaccine injection administered.
Experimental: NOR-107: GI.1/GII.4 (15/50/500) μg- MPL 15 μg,1-Dose; Eligible NOR-107 participants who had received IM hepatitis A vaccine on Day 1, followed by IM norovirus bivalent vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 15 µg MPL and 500 µg aluminium hydroxide, on Day 28 were enrolled at 3rd year post-primary vaccination in NOR-213 study.	Biological: NoV Vaccine; NoV vaccine injection administered.
Experimental: NOR-107: GI.1/GII.4 (50/50/500) μg- MPL 15 μg,1-Dose; Eligible NOR-107 participants who had received Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (50 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 15 µg MPL and 500 µg aluminium hydroxide, on Day 28 were enrolled at 3rd year post-primary vaccination in NOR-213 study.	Biological: NoV Vaccine; NoV vaccine injection administered.
Experimental: NOR-107: GI.1/GII.4 (15/15/500) μg,1-Dose; Eligible NOR-107 participants who had received Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminium hydroxide, on Day 28 were enrolled at 3rd year post-primary vaccination in NOR-213 study.	Biological: NoV Vaccine; NoV vaccine injection administered.
Experimental: NOR-107: GI.1/GII.4 (15/50/500) μg,1-Dose; Eligible NOR-107 participants who had received Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminium hydroxide, on Day 28 were enrolled at 3rd year post-primary vaccination in NOR-213 study.	Biological: NoV Vaccine; NoV vaccine injection administered.
Experimental: NOR-107: GI.1/GII.4 (50/50/500) μg,1-Dose; Eligible NOR-107 participants who had received Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (50 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminium hydroxide, on Day 28 were enrolled at 3rd year post-primary vaccination in NOR-213 study.	Biological: NoV Vaccine; NoV vaccine injection administered.
Experimental: NOR-107: GI.1/GII.4 (50/150/500) μg,1-Dose; Eligible NOR-107 participants who had received Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (50 µg of GI.1 norovirus VLP and 150 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminium hydroxide, on Day 28 were enrolled at 3rd year post-primary vaccination in NOR-213 study.	Biological: NoV Vaccine; NoV vaccine injection administered.
Experimental: NOR-107: GI.1/GII.4 (15/50/167) μg,1-Dose; Eligible NOR-107 participants who had received Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 167 µg aluminium hydroxide, on Day 28 were enrolled at 3rd year post-primary vaccination in NOR-213 study.	Biological: NoV Vaccine; NoV vaccine injection administered.
Experimental: NOR-107: GI.1/GII.4 (15/50/500) μg,2-Dose; Eligible NOR-107 participants who had received Norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminium hydroxide, IM, on Day 1 and Day 28 were enrolled at 3rd year post-primary vaccination in NOR-213 study.	Biological: NoV Vaccine; NoV vaccine injection administered.
Experimental: NOR-107: GI.1/GII.4 (50/150/500) μg,2-Dose; Eligible NOR-107 participants who had received Norovirus bivalent VLP vaccine (50 µg of GI.1 norovirus VLP and 150 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminium hydroxide, IM, on Day 1 and Day 28 were enrolled at 3rd year post-primary vaccination in NOR-213 study.	Biological: NoV Vaccine; NoV vaccine injection administered.
Experimental: NOR-107: GI.1/GII.4 (15/50/167) μg,2-Dose; Eligible NOR-107 participants who had received Norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 167 µg aluminium hydroxide, IM, on Day 1 and Day 28 were enrolled at 3rd year post-primary vaccination in NOR-213 study.	Biological: NoV Vaccine; NoV vaccine injection administered.
Experimental: NOR-210: GI.1/GII.4 (15/50/500) µg, 1-Dose; Eligible NOR-210 participants who had received Norovirus GI.1/GII.4 bivalent VLP vaccine NoV Vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP, adjuvanted with 500 µg aluminium hydroxide), IM injection, once on Day 1 were enrolled at 2nd year post-primary vaccination in NOR-213 study.	Biological: NoV Vaccine; NoV vaccine injection administered.
Experimental: NOR-204: GI.1/GII.4 (15/50/500) µg - MPL 15 µg, 1-Dose; Eligible NOR-204 participants who had received Norovirus bivalent placebo-matching vaccine, intramuscularly (IM), on Day 1, followed by norovirus (NoV) [15 μg of GI.1 and 50 μg of GII.4 bivalent virus-like particle (VLP)] adjuvanted with 500 µg aluminium hydroxide and 15 μg of monophosphoryl lipid A (MPL) (Composition B), on Day 29 were enrolled at 2nd year post-primary vaccination in NOR-213 study.	Biological: NoV Vaccine; NoV vaccine injection administered.
Experimental: NOR-204: GI.1/GII.4 (15/50/500) µg, 1-Dose (Age: 60-94 yrs); Eligible NOR-204 participants of age 60-94 years who had received Norovirus bivalent placebo-matching vaccine, IM, on Day 1, followed by norovirus (NoV) [15 μg of GI.1 and 50 μg of GII.4 bivalent virus-like particle (VLP)] adjuvanted with 500 µg aluminium hydroxide (Composition A), on Day 29 were enrolled at 2nd year post-primary vaccination in NOR-213 study.	Biological: NoV Vaccine; NoV vaccine injection administered.
Experimental: NOR-204: GI.1/GII.4 (15/50/500) µg, 1-Dose (Age: 18-49 yrs); Eligible NOR-204 participants of age 18-49 years who had received Norovirus bivalent placebo-matching vaccine, IM, on Day 1, followed by norovirus (NoV) [15 μg of GI.1 and 50 μg of GII.4 bivalent virus-like particle (VLP)] adjuvanted with 500 µg aluminium hydroxide (Composition A), on Day 29 were enrolled at 2nd year post-primary vaccination in NOR-213 study.	Biological: NoV Vaccine; NoV vaccine injection administered.
Experimental: NOR-204: GI.1/GII.4 (15/50/500) µg - MPL 15 µg, 2-Dose; Eligible NOR-204 participants who had received Norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminium hydroxide and 15 μg of MPL (Composition B), IM, on Day 1 and Day 29 were enrolled at 2nd year post-primary vaccination in NOR-213 study.	Biological: NoV Vaccine; NoV vaccine injection administered.
Experimental: NOR-204: GI.1/GII.4 (15/50/500) µg, 2-Dose; Eligible NOR-204 participants who had received Norovirus bivalent placebo-matching vaccine (15 μg of GI.1 50 μg of GII.4 bivalent VLP) adjuvanted with 500 µg aluminium hydroxide (Composition A) IM, on Day 1 and Day 29 were enrolled at 2nd year post-primary vaccination in NOR-213 study.	Biological: NoV Vaccine; NoV vaccine injection administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Blocking Titers 50 Percent (%) (GMBT50) of Anti-norovirus GI.1 VLP Antibodies as Measured by Histo-Blood Group Antigen HBGA Blocking Assay	GMBT50 of anti-norovirus GI. VLP antibody titers as measured by the histo-blood group antigen (HBGA) blocking assay. Data reported for up to Year 5 was collected at Baseline (NOR-107, NOR-210, NOR-204) , at Days 28 (NOR-107), 29 (NOR-204 and NOR-210), Day 36 (NOR-204), Day 56 (NOR-107) and Day 57 (NOR-204), Day 208 (NOR-107) and Day 211 (NOR-204), Year 2 (NOR-204 and NOR-210) Years 3, 4 and 5 (NOR-107, NOR-210, NOR-204)	Baseline up to Year 2 post-primary vaccination of initial study NOR-107, NOR-210 NOR-204 and up to Year 5 of this extension study
Geometric Mean Blocking Titer (GMBT50) of Anti-norovirus GII.4 VLP Antibodies as Measured by HBGA Blocking Assay	GMBT50 of anti-norovirus GII.4 VLP antibody titers as measured by the HBGA blocking assay. Data reported for up to Year 5 was collected at Baseline (NOR-107, NOR-210, NOR-204), at Days 28 (NOR-107), 29 (NOR-204 and NOR-210), Day 36 (NOR-204), Day 56 (NOR-107) and Day 57 (NOR-204), Day 208 (NOR-107) and Day 211 (NOR-204), Year 2 (NOR-204 and NOR-210) Years 3 4 and 5 (NOR-107,NOR-210, NOR-204) .	Baseline up to Year 2 post-primary vaccination of initial study NOR-107, NOR-210 NOR-204 and up to Year 5 of this extension study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Titers (GMT) of Anti-norovirus GI.1 VLP Antibodies as Measured by Total Immunoglobulin (Pan-Ig) Enzyme-linked Immunosorbent Assay (ELISA)	GMT of anti-norovirus GI.1 VLP antibody titers as measured by total immunoglobulin (pan-Ig) enzyme-linked immunoassay (ELISA). Data reported for up to Year 5 was collected at Baseline (NOR-107, NOR-210, NOR-204), at Days 28 (NOR-107), 29 (NOR-204 and NOR-210), Day 36 (NOR-204), Day 56 (NOR-107) and Day 57 (NOR-204), Day 208 (NOR-107) and Day 211 (NOR-204), Year 2 (NOR-204 and NOR-210) Years 3, 4 and 5(NOR-107,NOR-210, NOR-204).	Baseline up to Year 2 post-primary vaccination of initial study NOR-107, NOR-210 NOR-204 and up to Year 5 of this extension study
Geometric Mean Titers (GMT) of Anti-norovirus GII.4 VLP Antibodies as Measured by Pan-Ig ELISA	GMT of anti-norovirus GII.4 VLP antibody titers as measured by pan-Ig ELISA. Data reported for up to Year 5 was collected at Baseline (NOR-107,NOR-210, NOR-204), at Days 28 (NOR-107), 29 (NOR-204 and NOR-210), Day 36 (NOR-204), Day 56 (NOR-107) and Day 57 (NOR-204), Day 208 (NOR-107) and Day 211 (NOR-204), Year 2 (NOR-204 and NOR-210) Years 3, 4 and 5 (NOR-107,NOR-210, NOR-204).	Baseline up to Year 2 post-primary vaccination of initial study NOR-107, NOR-210 NOR-204 and up to Year 5 of this extension study

Collaborators and Investigators

• Sponsor: Takeda

Study record dates

Study Major Dates

• Study Start (Actual): February 21, 2017
• Primary Completion (Actual): July 22, 2021
• Study Completion (Actual): July 22, 2021

Study Registration Dates

• First Submitted: January 31, 2017
• First Submitted That Met QC Criteria: January 31, 2017
• First Posted (Estimate): February 1, 2017

Study Record Updates

• Last Update Posted (Actual): November 9, 2022
• Last Update Submitted That Met QC Criteria: November 7, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Drug Therapy
• Other Study ID Numbers: NOR-213; 2016-004288-37 (EudraCT Number); U1111-1189-7907 (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; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (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