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NCT02142504

Safety and Immunogenicity of Norovirus Bivalent Virus-Like Particle Vaccine in Healthy Adults

Completed Phase 2 Results posted Last updated 21 August 2017
What this trial tests

Phase 2 trial testing Norovirus Bivalent VLP Vaccine in Norovirus Prevention in 454 participants. Completed in 6 January 2016.

Timeline
15 May 2014
Primary endpoint
6 January 2016
6 January 2016

Quick facts

Lead sponsorTakeda
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposeprevention
Enrollment454
Start date15 May 2014
Primary completion6 January 2016
Estimated completion6 January 2016
Sites10 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Takeda — full company profile →

Who can join

Adults 18 to 49, any sex, with Norovirus Prevention. 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.

Percentage of Participants With Solicited Local Adverse Events (AEs) at Injection Site After the First Injection Primary · Days 1 through 7

Solicited local AEs at injection site are defined as: pain, erythema, induration, and swelling that occurred within 7 days after the primary injection.

Any Solicited Local AEs
GroupValue95% CI
Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)7.8
GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)64.1
GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)72.7
Pain
GroupValue95% CI
Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)7.8
GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)64.1
GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)72.7
Erythema
GroupValue95% CI
Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)0
GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)0
GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)0.6
Induration
GroupValue95% CI
Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)0
GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)1.4
GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)1.3
Swelling
GroupValue95% CI
Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)0
GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)2.1
GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)0.6
Percentage of Participants With Solicited Systemic Adverse Events (AEs) After the First Injection Primary · Days 1 through 7

Solicited systemic AEs are defined as: headache, fatigue, myalgia, arthralgia, vomiting, and diarrhea that occurred within 7 days after the primary injection.

Any Solicited Systemic AEs
GroupValue95% CI
Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)26.8
GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)33.1
GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)45.5
Headache
GroupValue95% CI
Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)16.3
GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)15.9
GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)18.2
Fatigue
GroupValue95% CI
Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)17.0
GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)15.9
GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)16.2
Myalgia
GroupValue95% CI
Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)7.2
GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)19.3
GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)25.3
Arthralgia
GroupValue95% CI
Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)3.3
GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)4.8
GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)7.8
Vomiting
GroupValue95% CI
Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)1.3
GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)1.4
GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)1.9
Diarrhea
GroupValue95% CI
Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)7.8
GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)7.6
GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)10.4
Percentage of Participants With Elevated Daily Oral Temperature (Fever) After the First Injection Primary · Days 1 through 7

Fever is defined as greater than or equal to 38°C (100.4°F). Oral body temperature measurement was performed using the thermometer provided by the site for 7 days after each injection. The highest body temperature observed each day was recorded on the Diary Card also provided by the site.

GroupValue95% CI
Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)0
GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)0.7
GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)0
Percentage of Participants With Unsolicited Adverse Events (AEs) After the First Injection Primary · Days 1 through 28

Unsolicited AEs are any AEs that are not solicited local or systemic AEs, as defined by this study.

GroupValue95% CI
Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)23.5
GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)16.6
GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)21.4
Percentage of Participants With Serious Adverse Events (SAEs) After the First Injection Primary · From first injection (Day 1) to second injection pre-dose (Up to Day 365)

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.

GroupValue95% CI
Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)1.3
GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)2.1
GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)3.2
Percentage of Participants With Serious Adverse Events (SAEs) After the Second Injection Primary · From second injection (Day 365) to 6 months after second injection (Up to Day 545)

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.

GroupValue95% CI
Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)1.6
GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)0.9
GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)0.9
Percentage of Participants With Adverse Events of Special Interest (AESI) After the First Injection Primary · From first injection (Day 1) to second injection pre-dose (Up to Day 365)

AESIs are AEs that are not solicited local or systemic AEs, they are predefined AEs that required close monitoring and prompt reporting to the sponsor. AESI included protocol specified Cardiac Disorders, Gastrointestinal Disorders, Immune System Disorders, Infections and Infestations, Musculoskeletal and Connective Tissue Diseases, Neuroinflammatory Disorders, Renal and Urinary Disorders, Skin Disorders, Thyroid Disorders, Vascular Disorders and Other Disorders.

GroupValue95% CI
Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)1.3
GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)2.1
GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)1.3
Percentage of Participants With Adverse Events of Special Interest (AESI) After the Second Injection Primary · From second injection (Day 365) to 6 months after second injection (Up to Day 545)

AESIs are AEs that are not solicited local or systemic AEs, they are predefined AEs that required close monitoring and prompt reporting to the sponsor. AESI included protocol specified Cardiac Disorders, Gastrointestinal Disorders, Immune System Disorders, Infections and Infestations, Musculoskeletal and Connective Tissue Diseases, Neuroinflammatory Disorders, Renal and Urinary Disorders, Skin Disorders, Thyroid Disorders, Vascular Disorders and Other Disorders.

GroupValue95% CI
Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)3.2
GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)0
GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)0.9
Percentage of Participants With Any Adverse Event (AE) Leading to Withdrawal From the Study Primary · Unsolicited AEs 28 days after each injection (Days 1 to 28 and Days 365 to 393), and Serious Adverse Events (SAEs) throughout the trial (Up to Day 545)

Withdrawal due to an AE occurred if the participant experienced an AE that required early termination because continued participation imposed an unacceptable risk to the participant's health or the participant was unwilling to continue because of the AE.

GroupValue95% CI
Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)1.3
GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)1.4
GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)2.6
Percentage of Participants With Solicited Local Adverse Events (AEs) at Injection Site After the Second Injection Secondary · Days 365 through 371

Solicited local AEs at injection site are defined as: pain, erythema, induration, and swelling that occurred within 7 days after the vaccination on Day 365.

Any Solicited Local AEs
GroupValue95% CI
Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)41.3
GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)41.3
GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)44.0
Pain
GroupValue95% CI
Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)41.3
GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)41.3
GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)44.0
Erythema
GroupValue95% CI
Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)0.8
GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)0.9
GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)0
Induration
GroupValue95% CI
Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)0
GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)0
GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)0
Swelling
GroupValue95% CI
Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)0
GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)2.8
GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)0
Percentage of Participants With Solicited Systemic Adverse Events (AEs) After the Second Injection Secondary · Days 365 through 371

Solicited systemic AEs are defined as: headache, fatigue, myalgia, arthralgia, vomiting, and diarrhea that occurred within 7 days after the vaccination on Day 365.

Any Solicited Systemic AEs
GroupValue95% CI
Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)28.6
GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)25.7
GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)31.9
Headache
GroupValue95% CI
Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)11.9
GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)11.0
GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)14.7
Fatigue
GroupValue95% CI
Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)11.1
GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)14.7
GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)17.2
Myalgia
GroupValue95% CI
Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)15.1
GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)15.6
GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)14.7
Arthralgia
GroupValue95% CI
Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)0.8
GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)7.3
GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)6.0
Vomiting
GroupValue95% CI
Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)2.4
GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)1.8
GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)1.7
Diarrhea
GroupValue95% CI
Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)4.0
GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)7.3
GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)8.6
Percentage of Participants With Elevated Daily Oral Temperature (Fever) After the Second Injection Secondary · Days 365 through 371

Fever is defined as greater than or equal to 38°C (100.4°F). Oral body temperature measurement was performed using the thermometer provided by the site for 7 days after each vaccination. The highest body temperature observed each day was recorded on the Diary Card also provided by the site.

GroupValue95% CI
Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)0
GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)0.9
GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)2.6

Adverse events — posted to ClinicalTrials.gov

Time frame: Unsolicited AEs 28 days after each injection (Days 1 to 28 and Days 365 to 393), and Serious Adverse Events (SAEs) throughout the trial (Up to Day 545). Reporting threshold: 2%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)
Serious: 4/153 (3%)
Deaths:
GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)
Serious: 4/145 (3%)
Deaths:
GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)
Serious: 6/154 (4%)
Deaths:

Serious adverse events (19 terms)

ReactionSystemSaline Placebo + GI.1/GII.…GI.1/GII.4 15/50 μg - MPL …GI.1/GII.4 50/50 μg - MPL …
Cardiac arrestCardiac disorders
Basedow's diseaseEndocrine disorders
Retinal detachmentEye disorders
Injection site painGeneral disorders
Kidney infectionInfections and infestations
SepsisInfections and infestations
Urinary tract infectionInfections and infestations
Hip fractureInjury, poisoning and procedural complications
Intentional overdoseInjury, poisoning and procedural complications
Pelvic fractureInjury, poisoning and procedural complications
Rib fractureInjury, poisoning and procedural complications
Road traffic accidentInjury, poisoning and procedural complications
Musculoskeletal painMusculoskeletal and connective tissue disorders
MigraineNervous system disorders
Neuralgic amyotrophyNervous system disorders
Abortion spontaneousPregnancy, puerperium and perinatal conditions
DepressionPsychiatric disorders
Post-traumatic stress disorderPsychiatric disorders
SchizophreniaPsychiatric disorders
Other adverse events (14 terms — click to expand)

ReactionSystemSaline Placebo + GI.1/GII.…GI.1/GII.4 15/50 μg - MPL …GI.1/GII.4 50/50 μg - MPL …
HeadacheNervous system disorders
NauseaGastrointestinal disorders
NasopharyngitisInfections and infestations
MyalgiaMusculoskeletal and connective tissue disorders
DiarrhoeaGastrointestinal disorders
FatigueGeneral disorders
Injection site bruisingGeneral disorders
Back painMusculoskeletal and connective tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders
Sinus headacheNervous system disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
Abdominal pain upperGastrointestinal disorders
Injection site painGeneral disorders
DizzinessNervous system disorders

Most-reported serious reactions: Cardiac arrest, Basedow's disease, Retinal detachment, Injection site pain, Kidney infection, Sepsis, Urinary tract infection, Hip fracture.

Data from ClinicalTrials.gov NCT02142504 adverse events section.

Sponsor's own description

The purpose of this study is to evaluate the safety of the norovirus bivalent virus-like particle (VLP) vaccine for further development by assessing the rates of serious adverse events (SAEs), unsolicited adverse events (AEs), solicited local and solicited systemic AEs, Adverse Events of Special Interest (AESIs) and AEs leading to participant's withdrawal from the trial.

Publications & conference data

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

  1. Rapid Responses to 2 Virus-Like Particle Norovirus Vaccine Candidate Formulations in Healthy Adults: A Randomized Controlled Trial.
    Atmar RL, Baehner F, Cramer JP, Song E, et al · · 2016 · cited 48× · PMID 27354368 · DOI 10.1093/infdis/jiw259
  2. Norovirus immunology: Of mice and mechanisms.
    Newman KL, Leon JS. · · 2015 · cited 39× · PMID 26256101 · DOI 10.1002/eji.201545512
  3. 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
  4. Virus-like Particles as Antiviral Vaccine: Mechanism, Design, and Application.
    Zhang L, Xu W, Ma X, Sun X, et al · · 2023 · cited 28× · PMID 36627930 · DOI 10.1007/s12257-022-0107-8
  5. Persistence of Antibodies to 2 Virus-Like Particle Norovirus Vaccine Candidate Formulations in Healthy Adults: 1-Year Follow-up With Memory Probe Vaccination.
    Atmar RL, Baehner F, Cramer JP, Lloyd E, et al · · 2019 · cited 25× · PMID 31001633 · DOI 10.1093/infdis/jiz170
  6. 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
  7. 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
  8. Unraveling the interplay between norovirus infection, gut microbiota, and novel antiviral approaches: a comprehensive review.
    Bai GH, Tsai MC, Lin SC, Hsu YH, et al · · 2023 · cited 7× · PMID 37485533 · DOI 10.3389/fmicb.2023.1212582

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