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

Phase 2

Completed

• Conditions: Norovirus; Healthy Volunteers
• Interventions: Biological: NoV Vaccine

• Registration Number: NCT03039790
• Lead Sponsor: Takeda

Brief Summary

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

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 Timeline

• Study First Submitted: 2017-01-31
• Study First Submitted QC: 2017-01-31
• Study First Posted: 2017-02-01
• Study Start: 2017-02-21
• Primary Completion: 2021-07-22
• Study Completion: 2021-07-22
• Results First Submitted: 2022-07-21
• Results First Submitted QC: 2022-09-08
• Results First Posted: 2022-10-06
• Status Verified: 2022-11
• Last Update Submitted: 2022-11-07
• Last Update Posted: 2022-11-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 528

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
NOR-107: GI.1/GII.4 (50/50/500) μg- MPL 50 μg,1-Dose	NoV Vaccine	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.
NOR-107: GI.1/GII.4 (15/50/500) μg- MPL 50 μg,1-Dose	NoV Vaccine	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.
NOR-107: GI.1/GII.4 (15/50/500) μg,2-Dose	NoV Vaccine	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.
NOR-107: GI.1/GII.4 (15/15/500) μg- MPL 15 μg,1-Dose	NoV Vaccine	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.
NOR-107: GI.1/GII.4 (50/150/500) μg,1-Dose	NoV Vaccine	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.
NOR-107: GI.1/GII.4 (15/50/167) μg,2-Dose	NoV Vaccine	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.
NOR-210: GI.1/GII.4 (15/50/500) µg, 1-Dose	NoV Vaccine	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.
NOR-107: GI.1/GII.4 (50/50/500) μg- MPL 15 μg,1-Dose	NoV Vaccine	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.
NOR-107: GI.1/GII.4 (15/15/500) μg,1-Dose	NoV Vaccine	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.
NOR-107: GI.1/GII.4 (50/150/500) μg,2-Dose	NoV Vaccine	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.
NOR-204: GI.1/GII.4 (15/50/500) µg, 1-Dose (Age: 18-49 yrs)	NoV Vaccine	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.
NOR-107: GI.1/GII.4 (15/15/500) μg- MPL 50 μg,1-Dose	NoV Vaccine	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.
NOR-107: GI.1/GII.4 (15/50/500) μg- MPL 15 μg,1-Dose	NoV Vaccine	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.
NOR-107: GI.1/GII.4 (15/50/500) μg,1-Dose	NoV Vaccine	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.
NOR-107: GI.1/GII.4 (50/50/500) μg,1-Dose	NoV Vaccine	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.
NOR-204: GI.1/GII.4 (15/50/500) µg - MPL 15 µg, 1-Dose	NoV Vaccine	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.
NOR-204: GI.1/GII.4 (15/50/500) µg, 1-Dose (Age: 60-94 yrs)	NoV Vaccine	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.
NOR-107: GI.1/GII.4 (15/50/167) μg,1-Dose	NoV Vaccine	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.
NOR-204: GI.1/GII.4 (15/50/500) µg, 2-Dose	NoV Vaccine	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.
NOR-204: GI.1/GII.4 (15/50/500) µg - MPL 15 µg, 2-Dose	NoV Vaccine	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.

Primary Outcome Measures

Name	Time	Method
Geometric Mean Blocking Titers 50 Percent (%) (GMBT50) of Anti-norovirus GI.1 VLP Antibodies as Measured by Histo-Blood Group Antigen HBGA Blocking Assay	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	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)
Geometric Mean Blocking Titer (GMBT50) of Anti-norovirus GII.4 VLP Antibodies as Measured by HBGA Blocking Assay	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	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) .

Secondary Outcome Measures

Name	Time	Method
Geometric Mean Titers (GMT) of Anti-norovirus GII.4 VLP Antibodies as Measured by Pan-Ig ELISA	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	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).
Geometric Mean Titers (GMT) of Anti-norovirus GI.1 VLP Antibodies as Measured by Total Immunoglobulin (Pan-Ig) Enzyme-linked Immunosorbent Assay (ELISA)	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	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).

Trial Locations

Locations (11)

Simon-Williamson Clinic/Synexus Clinical Research US, Inc; 🇺🇸 Birmingham, Alabama, United States

Synexus Clinical Research US, Inc/Southwest Family Medicine; 🇺🇸 Littleton, Colorado, United States

Miami Research Associates; 🇺🇸 Miami, Florida, United States

Johnson County Clin-Trials; 🇺🇸 Lenexa, Kansas, United States

St. Louis University, School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

University of Rochester; 🇺🇸 Rochester, New York, United States

Benchmark Research Austin; 🇺🇸 Austin, Texas, United States

Universiteit Antwerpen; 🇧🇪 Antwerpen, Belgium

Universitair Ziekenhuis Gent; 🇧🇪 Gent, Belgium

Regional Clinical Research Inc.; 🇺🇸 Endwell, New York, United States

Synexus Clinical Research US, Inc./Fountain Hills Family Practice, P.C.; 🇺🇸 Fountain Hills, Arizona, United States