NCT02475278

Serologic Assay Validation, Proficiency Testing, Safety and Immunogenicity of Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine

Completed Phase 2 Results posted Last updated 22 February 2018

What this trial tests

Phase 2 trial testing NoV GI.1/GII.4 Bivalent VLP Vaccine in Norovirus in 50 participants. Completed in 9 September 2015.

Timeline

26 February 2015

Primary endpoint
7 April 2015

9 September 2015

Quick facts

Lead sponsor	Takeda
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	other
Enrollment	50
Start date	26 February 2015
Primary completion	7 April 2015
Estimated completion	9 September 2015
Sites	1 location across United States

Drugs / interventions tested

• NoV GI.1/GII.4 Bivalent VLP Vaccine — full drug profile →

Conditions studied

• Norovirus — all drugs for Norovirus →
• Healthy Participants — all drugs for Healthy Participants →

Sponsor

Takeda — full company profile →

Who can join

Adults 18 to 49, any sex, with Norovirus or Healthy Participants. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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 Primary · Day 8

Serum samples were obtained for assay validation of the pan-Ig enzyme-linked immuno-sorbent assay (ELISA) and the histoblood group antigen (HBGA) binding assay. The number of participants with assessments for both the GI.1 VLP and GII.4 VLP antibodies and by both the pan-Ig ELISA and the HBGA binding assay, and with values available at Baseline and Day 8 are reported.

Group	Value	95% CI
NoV Vaccine	48

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 Primary · Day 15

Serum samples were obtained to establish proficiency panels for the pan-Ig ELISA and the HBGA binding assay. The number of participants with assessments for both the GI.1 VLP and GII.4 VLP antibodies and by both the pan-Ig ELISA and the HBGA binding assay, and with values available at Baseline and Day 15 are reported.

Group	Value	95% CI
NoV Vaccine	48

Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) by Maximum Severity Secondary · Days 1 through 7

Safety assessment included collection of solicited local AEs for 7 days following vaccination (including the day of vaccination) by using diary cards. Solicited local injection site AEs are defined as pain, erythema (redness), induration and swelling. Pain is summarized as either none or any, where 'any' will be broken down into the following severity categories: mild, moderate, severe. Erythema, swelling and induration are recorded as yes or no, where the definition of 'yes' is any area ≥2.5 cm; and 'yes' is further broken down into the following severity categories: ≥2.5 cm - ≤5.0 cm (mild i

Pain, Any

Group	Value	95% CI
NoV Vaccine	54.0

Pain, Mild

Group	Value	95% CI
NoV Vaccine	44.0

Pain, Moderate

Group	Value	95% CI
NoV Vaccine	10.0

Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Maximum Severity Secondary · Days 1 through 7

Safety assessment included collection of solicited systemic AEs for 7 days following vaccination (including the day of vaccination) by using diary cards. Solicited systemic AEs are defined as headache, fatigue, myalgia, arthralgia, vomiting and diarrhea and are summarized as either none or any, where 'any' will be broken down into the following severity categories: mild, moderate, severe. Solicited systemic AEs are presented as the percentage of participants experiencing a solicited systemic AE, by AE, overall and by severity, using the participant's worst reported severity grade. Only categor

Headache, Any

Group	Value	95% CI
NoV Vaccine	24.0

Headache, Mild

Group	Value	95% CI
NoV Vaccine	18.0

Headache, Moderate

Group	Value	95% CI
NoV Vaccine	6.0

Fatigue, Any

Group	Value	95% CI
NoV Vaccine	34.0

Fatigue, Mild

Group	Value	95% CI
NoV Vaccine	30.0

Fatigue, Moderate

Group	Value	95% CI
NoV Vaccine	4.0

Myalgia, Any

Group	Value	95% CI
NoV Vaccine	12.0

Myalgia, Mild

Group	Value	95% CI
NoV Vaccine	12.0

Percentage of Participants With Elevated Daily Oral Temperature Secondary · Days 1 to 7 days after vaccination

Safety assessment included measurement of body temperature for 7 days following vaccination (including the day of vaccination) by using diary cards. Participants recorded the highest body temperature observed each day in a daily diary. The highest body temperature measurement per participant across Day 1 to Day 7 was categorized as fever present (≥100.4ºF, ≥38ºC) or fever absent (\<100.4ºF, \<38ºC).

Group	Value	95% CI
NoV Vaccine	0.0

Percentage of Participants With Unsolicited Adverse Events (AEs) by Maximum Severity Secondary · Days 1 through 28

An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. Unsolicited AEs are any AEs that are not solicited local or systemic AEs, as defined by this study. Unsolicited AEs are presented as the percentage of participants experiencing at least one AE, overall and by severity, using the participant's worst reported severity grade. Only categories for which there was at least 1 participant are reported.

Unsolicited Adverse Events, Any

Group	Value	95% CI
NoV Vaccine	22.0

Unsolicited Adverse Events, Mild

Group	Value	95% CI
NoV Vaccine	14.0

Unsolicited Adverse Events, Moderate

Group	Value	95% CI
NoV Vaccine	6.0

Unsolicited Adverse Events, Severe

Group	Value	95% CI
NoV Vaccine	2.0

Percentage of Participants Experiencing Serious Adverse Events Secondary · Day 1 up to Day 183

A serious adverse event (SAE) is any untoward medical occurrence or effect that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability / incapacity, is a congenital anomaly / birth defect or is medically important due to other reasons than the above mentioned criteria.

Group	Value	95% CI
NoV Vaccine	2.0

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 Primary · Day 29

Serum samples were obtained to establish proficiency panels for the pan-Ig ELISA and the HBGA binding assay. The number of participants with assessments for both the GI.1 VLP and GII.4 VLP antibodies and by both the pan-Ig ELISA and the HBGA binding assay, and with values available at Baseline and Day 29 are reported.

Group	Value	95% CI
NoV Vaccine	46

Adverse events — posted to ClinicalTrials.gov

Time frame: Unsolicited AEs 28 days after vaccination (Day 1 to 28) and Serious Adverse Events (SAEs) throughout the trial (Up to Day 183).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

NoV Vaccine

Serious: 1/50 (2%)

Deaths: —

Serious adverse events (1 terms)

Reaction	System	NoV Vaccine
Unevaluable event	General disorders	—

Other adverse events (1 terms — click to expand)

Reaction	System	NoV Vaccine
Rhinitis	Infections and infestations	—

Most-reported serious reactions: Unevaluable event.

Data from ClinicalTrials.gov NCT02475278 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Comparison of Microneutralization and Histo-Blood Group Antigen-Blocking Assays for Functional Norovirus Antibody Detection.
   Atmar RL, Ettayebi K, Ayyar BV, Neill FH, et al · · 2020 · cited 52× · PMID 31613328 · DOI 10.1093/infdis/jiz526
2. Norovirus replication, host interactions and vaccine advances.
   Prasad BVV, Atmar RL, Ramani S, Palzkill T, et al · · 2025 · cited 33× · PMID 39824927 · DOI 10.1038/s41579-024-01144-9
3. Prophylactic vaccine delivery systems against epidemic infectious diseases.
   Pan C, Yue H, Zhu L, Ma GH, et al · · 2021 · cited 28× · PMID 34280513 · DOI 10.1016/j.addr.2021.113867
4. Epidemiology and evolution of Norovirus in China.
   Wei N, Ge J, Tan C, Song Y, et al · · 2021 · cited 20× · PMID 34495811 · DOI 10.1080/21645515.2021.1961465
5. An Exploratory Study of the Salivary Immunoglobulin A Responses to 1 Dose of a Norovirus Virus-Like Particle Candidate Vaccine in Healthy Adults.
   Atmar RL, Cramer JP, Baehner F, Han C, et al · · 2019 · cited 19× · PMID 30203081 · DOI 10.1093/infdis/jiy529
6. In Depth Breadth Analyses of Human Blockade Responses to Norovirus and Response to Vaccination.
   Haynes J, Perry V, Benson E, Meeks A, et al · · 2019 · cited 11× · PMID 31035476 · DOI 10.3390/v11050392
7. Virus-like Particles for TEM Regulation and Antitumor Therapy.
   Yang Z, Chi Y, Bao J, Zhao X, et al · · 2022 · cited 4× · PMID 36547564 · DOI 10.3390/jfb13040304
8. Persistence of the Immune Response to an Intramuscular Bivalent (GI.1/GII.4) Norovirus Vaccine in Adults.
   Leroux-Roels G, Atmar RL, Cramer JP, Escudero I, et al · · 2025 · cited 3× · PMID 39852862 · DOI 10.3390/vaccines13010082