GastroenteritisPhase 1NCT01168401

Bivalent Norovirus Vaccine Study

A Phase 1 study testing NoV GI.1/GII.4 Bivalent VLP Vaccine and Saline in people with Gastroenteritis, run by Takeda at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Randomized, multi-site, dose-escalation study of the safety and immunogenicity of four dosage levels of Intramuscular (IM) Norovirus Bivalent VLP Vaccine adjuvanted with MPL and Al(OH)3 compared to controls. Participants will receive two doses, by IM injection, 28 days apart. Read more about this study

Who is it for?: Ages 18 to 85 yearsHealthy volunteers can take part
Conditions the study is for: Gastroenteritis
What is being tested?: NoV GI.1/GII.4 Bivalent VLP Vaccine and Saline
Type of treatment: Vaccines
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 102 participants
Where: 3 sitesUnited States
Study dates: 3 Sep 2010to 9 Jan 2013
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 85 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

Participants must meet all of the inclusion criteria listed below:
Signed written informed consent.
Age:
Cohort A: 18-49 years, inclusive
Cohort B: 50-64 years, inclusive
Cohort C: 65-85 years, inclusive

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Cohort D: 18-49 years, inclusive
Health Status:
Cohort A and D: In good health as determined by a screening evaluation that includes vital signs, medical history, and physical exam within 45 days before administration of IM Norovirus Bivalent VLP Vaccine or control.
Cohorts B and C: In good health as determined by a screening evaluation that includes vital signs, medical history, and physical exam within 45 days before administration of IM Norovirus Bivalent VLP Vaccine or control. Any existing medical diagnoses or conditions must be stable based on medical history and targeted physical examination. A stable medical condition is defined as: (A) Clinically acceptable health outcomes for the specific condition over the prior 6 months and (B) No change in prescription medication(s), dose, or frequency over the prior 3 months. Acceptable changes in medications are: a change of health care provider or insurance company or that is made for financial reasons as long as the medications are in the same class and/or a change due to improvement in a disease outcome.
Expressed interest and availability to fulfill the study requirements.
Female participants must be of non-childbearing potential (surgically sterile or post-menopausal for greater than or equal to [>=] 12 months), or if of childbearing potential (as determined by the investigator) must be practicing abstinence or using an effective licensed method of birth control (example oral contraceptives; diaphragm or condom in combination with contraceptive jelly, cream, or foam; intrauterine contraceptive device, or Depo-Provera; skin patch; vaginal ring or cervical cap) for 30 days prior to vaccination and must agree to continue such precautions for at least 60 days after the last vaccination. A woman is eligible if she is monogamous with a male who has had a vasectomy. Male participants must agree not to father a child for at least 60 days after the last vaccination and to practice abstinence or use an effective method of birth control as noted above.
Agrees not to participate in another clinical trial with an investigational product for the entire duration of the study one year after the last study dose that is 393 days.
Agrees to storage of unused clinical specimens for an indefinite period of time for future norovirus research or research on other gastrointestinal pathogens.

Who cannot join

Participants who meet any of the exclusion criteria at baseline will be excluded from study participation. The exclusion criteria are:
History of any of the following medical illnesses:
Diabetes
Cancer (malignancy other than resolved/excised skin lesion)
Heart disease (hospitalization for a heart attack, arrhythmia, or syncope)
Unconsciousness (other than a single brief "concussion")

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Seizures (other than febrile seizures as a child less than [<] 5 years old)
Recurrent infections (more than 3 hospitalizations for invasive bacterial infections such as pneumonia or meningitis)
Any condition associated with immunodeficiency or participants taking immunosuppressant medication
Neuroinflamatory or auto-immune disease
Any current illness requiring daily medication other than the following:
Cohort A and D: Vitamins, birth control, anti-hypertensive medication, antihistamines or anti-depressant medication. The Principal Investigator (PI) should consult with the Central Safety Monitor and/or the sponsor for any clarification of medications allowable.
Cohorts B and C: Vitamins, birth control, anti-hypertensive medication, antihistamines or anti-depressant medication or any current illness requiring daily medication other than as noted above in inclusion criteria 3. The PI should consult with the Central Safety Monitor and/or the sponsor for any clarification of medications allowable.
Allergies or hypersensitivity to any component of the vaccine including MPL and Al(OH)3 adjuvants.
Any clinically significant abnormality detected on physical examination, including:
Murmur (other than a functional murmur)
Focal neurological abnormality
Hepatosplenomegaly
Lymphadenopathy
Jaundice
Hypertension (Blood Pressure [BP] greater than [>] 140/90 millimeter of mercury [mm Hg] on two separate days)
Any lab abnormality (per the site local laboratory), as listed below:
Absolute Neutrophil Count (ANC) outside the normal range (may be repeated if outside this limit)
Total white blood cells (WBC) outside the normal range (may be repeated if outside this limit)
Hemoglobin outside the normal range (may be repeated if outside this limit)
Platelet count outside the normal range (may be repeated if outside this limit)
Blood urea nitrogen (BUN) > upper limit of normal (ULN) (may be repeated if outside this limit)
Creatinine > ULN (may be repeated if outside this limit)
Glucose (fasting or random) outside the normal range (may be repeated if outside this limit)
Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) > ULN (may be repeated if outside this limit)
Positive serology for hepatitis C or Human Immunodeficiency Virus (HIV) antibody or hepatitis B surface antigen.
For women of child bearing potential, positive serum pregnancy test within 14 days and urine pregnancy test within 24 hours of administering either dose of IM Norovirus Bivalent VLP Vaccine or control.
Nursing mother.
Temperature >100.4 degree Fahrenheit (F) or symptoms of an acute self-limited illness such as an upper respiratory infection or gastroenteritis within 3 days of administration of IM Norovirus Bivalent VLP Vaccine or control.
Previous participation in a Norovirus vaccine or challenge study.
Study site personnel or their family members.
Significant history of psychiatric hospitalization, alcohol abuse, or illicit drug use in the prior 5 years.
Completion of an investigational vaccine or drug study within 28 days before administration of IM Norovirus Bivalent VLP Vaccine or control.
Have a history of receiving immunoglobulin or other blood product within the 3 months prior to vaccination in this study.
Other condition that in the clinical judgment of the investigator would jeopardize the safety or rights of a participant participating in the trial, would render the participant unable to comply with the protocol or would interfere with the evaluation of the vaccine.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

University of Rochester Medical Center
Rochester, New York, 14642
Navy Medical Research Center
Silver Springs, Maryland, 20910
Saint Louis University
St Louis, Missouri, 63104

Other trials in United States

About this study

Official title: Phase 1, Randomized Controlled Dose Escalation, Safety and Immunogenicity Study of Intramuscular Norovirus GI.1/GII.4 Bivalent Virus-Like Particle (VLP) Vaccine Adjuvanted With Monophosphoryl Lipid A (MPL) and Aluminum Hydroxide [Al(OH)3] in Adults

The hypotheses for this study are:

The incidence of adverse events after vaccination with IM Norovirus Bivalent VLP Vaccine will be similar to the incidence of adverse events after other IM vaccines including CERVARIX® which contains MPL and Al(OH)3.
Two doses of IM Norovirus Bivalent VLP Vaccine will be more immunogenic than one dose.
The post-vaccination serum antibody responses, the number of antibody secreting cells (ASC), including homing markers, and memory B-cell responses directed against norovirus antigens will be increased after IM Norovirus Bivalent VLP Vaccine compared to controls.

Conditions: Gastroenteritis
Being tested: NoV GI.1/GII.4 Bivalent VLP Vaccine, Saline
Keywords: Vaccine, norovirus, acute gastroenteritis
Medical subject headings: Gastroenteritis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

NoV GI.1/GII.4 Bivalent VLP VaccineBiological
2 Doses 28 days apart Cohort A: 18-49 Years
Cohort A1: IM Norovirus Bivalent GI.1/GII.4 VLP Vaccine (5/5 mcg)
Cohort A2: IM Norovirus Bivalent GI.1/GII.4 VLP Vaccine (15/15 mcg)
Cohort A3: IM Norovirus Bivalent GI.1/GII.4 VLP Vaccine (50/50 mcg)
Cohort A4: IM Norovirus Bivalent GI.1/GII.4 VLP Vaccine (150/150 mcg)
Cohort B: 50-64 Years IM Norovirus Bivalent GI.1/GII.4 VLP Vaccine (50/50 mcg)
Cohort C: 65-85 Years IM Norovirus Bivalent GI.1/GII.4 VLP Vaccine (50/50 mcg)
Cohort D: 18-49 Years IM Norovirus Bivalent GI.1/GII.4 VLP Vaccine (50/50 mcg)
SalineBiological
Two doses 28 days apart

Study groups in NCT01168401
Study group	Role	What they receive
NoV GI.1/GII.4 Bivalent VLP Vaccine	Experimental	Norovirus Bivalent GI.1 and GII.4 VLP Vaccine, adjuvanted with 50 microgram (mcg) MPL and 500 mcg Al(OH)3, IM, on Days 0 and 28. Receives: Biological: NoV GI.1/GII.4 Bivalent VLP Vaccine
Saline	Placebo comparator	Not described Receives: Biological: Saline

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With Solicited Local Adverse Events (AEs) Post Dose 1
The solicited local adverse events were reported using a memory aid. Pain was scaled as Mild (did not interfere with activity); Moderate (repeated use of non-narcotic pain reliever greater than (>) 24 hours [24h] or interfered with activity); and Severe (any use of narcotic pain reliever or prevented daily activity). Tenderness was scaled as Mild (mild discomfort to touch); Moderate (discomfort with movement); and Severe (significant discomfort at rest). Swelling and redness were scaled as Mild (2.5-5 centimeter [cm] and did not interfere with activity); Moderate (5.1-10 cm or interfered with activity); and Severe (>10 cm or prevented daily activity).
Measured: Day 0 up to Day 7
Number of Participants With Solicited Local AEs Post Dose 2
The solicited local adverse events were reported using a memory aid. Pain was scaled as Mild (did not interfered with activity); Moderate (repeated use of non-narcotic pain reliever >24h or interfered with activity); and Severe (any use of narcotic pain reliever or prevented daily activity). Tenderness was scaled as Mild (mild discomfort to touch); Moderate (discomfort with movement); and Severe (significant discomfort at rest). Swelling and redness were scaled as Mild (2.5-5 cm and did not interfere with activity); Moderate (5.1-10 cm or interfered with activity); and Severe (>10 cm or prevented daily activity).
Measured: Day 28 up to Day 35
Number of Participants With Solicited Systemic AEs Post Dose 1
Elevated oral temperature:Mild(38-38.4 Celsius[C]);Moderate(38.5-38.9 C);Severe(39-40 C).Headache:Mild(no interference with activity);Moderate(repeated use of non-narcotic pain reliever>24h/some interference with activity);Severe(significant;any use of narcotic pain reliever/prevented daily activity).Fatigue,Malaise:Mild(no interference with activity);Moderate(some interference with activity);Severe(significant;prevented daily activity).Diarrhea:Mild(2-3loose stools/<400gram[g]/24h);Moderate(4-5stools/400-800g/24h);Severe(>=6watery stools/>800g/24h/required intravenous[IV]hydration).Nausea/Vomiting:Mild(no interference with activity/1-2 episodes/24h);Moderate(some interference with activity/>2 episodes/24h);Severe(prevented daily activity,required IV hydration).Muscle ache,chills,joint ache,abdominal cramp/pain:Mild(no interference with activity);Moderate(some interference with activity,not required medical intervention);Severe(prevented daily activity,required medical intervention).
Measured: Day 0 up to Day 7
Number of Participants With Solicited Systemic AEs Post Dose 2
Elevated oral temperature:Mild(38-38.4 C);Moderate(38.5-38.9 C);Severe(39-40 C).Headache:Mild(no interference with activity);Moderate(repeated use of non-narcotic pain reliever>24h/some interference with activity);Severe(significant;any use of narcotic pain reliever/prevented daily activity).Fatigue,Malaise:Mild(no interference with activity);Moderate(some interference with activity);Severe(significant;prevented daily activity).Diarrhea:Mild(2-3loose stools/<400g/24h);Moderate(4-5stools/400-800g/24h);Severe(>=6watery stools/>800g/24h/required IV hydration).Nausea/Vomiting:Mild(no interference with activity/1-2 episodes/24h);Moderate(some interference with activity/>2 episodes/24h);Severe(prevented daily activity,required IV hydration).Muscle ache,chills,joint ache,abdominal cramp/pain:Mild(no interference with activity);Moderate(some interference with activity,not required medical intervention);Severe(prevented daily activity,required medical intervention).
Measured: Day 28 up to Day 35
Number of Participants With Unsolicited AEs Post Dose 1
Measured: Baseline up to Day 28 (Pre-dose 2)
Number of Participants With Unsolicited AEs Post Dose 2
Measured: Day 28 up to Day 56 (Post dose 2)
Number of Participants With Clinically Significant Change From Baseline in Markedly Abnormal Laboratory Values
The number of participants with any markedly abnormal standard safety laboratory values (serum chemistry or hematology) collected throughout study.
Measured: Baseline up to Day 35
Number of Participants With Serious Adverse Events (SAEs), Onset of Significant New Medical Conditions, Including Adverse Events of Special Interest (AESI)
Measured: Baseline up to 365 Days after post dose 2 (Day 393)

Secondary outcomes (12)

Geometric Mean Titer (GMT) of Serum Anti-norovirus GI.1 and GII.4 VLP Ig (Immunoglobulin) A
Run I was defined as the initial analysis performed once Day 56 post dose data was available. Run II was defined as final analysis performed after all later time points were achieved.
Measured: First (I) run: predose 1 and 7, 21, 28 days postdose (PD)1, and 7 and 28 days PD2; second (II) run: predose 1 and 28, 152 and 365 days PD2 (up to Day 393)
GMT of Serum Anti-norovirus GI.1 and GII.4 VLP IgG
Run I was defined as the initial analysis performed once Day 56 post dose data was available. Run II was defined as final analysis performed after all later time points were achieved.
Measured: I run: predose 1 and 7, 21, 28 days PD1, and 7 and 28 days PD2; II run: predose 1 and 28, 152 and 365 days PD2 (up to Day 393)
GMT of Serum Anti-norovirus GI.1 and GII.4 VLP IgM
Run I was defined as the initial analysis performed once Day 56 post dose data was available. Run II was defined as final analysis performed after all later time points were achieved.
Measured: I run: predose 1 and 7, 21, 28 days PD1, and 7 and 28 days PD2; II run: predose 1 and 28, 152 and 365 days PD2 (up to Day 393)
Geometric Mean Fold Rise (GMFR) of Serum Anti-norovirus GI.1 and GII.4 VLP IgA as Compared to Baseline
Run I was defined as the initial analysis performed once Day 56 post dose data was available. Run II was defined as final analysis performed after all later time points were achieved.
Measured: I run: 7, 21, 28 days PD1, 7 and 28 days PD2; II run: 28, 152 and 365 days PD2 (up to Day 393)
GMFR of Serum Anti-norovirus GI.1 and GII.4 VLP IgG as Compared to Baseline
Run I was defined as the initial analysis performed once Day 56 post dose data was available. Run II was defined as final analysis performed after all later time points were achieved.
Measured: I run: 7, 21, 28 days PD1, 7 and 28 days PD2; II run: 28, 152 and 365 days PD2 (up to Day 393)
GMFR of Serum Anti-norovirus GI.1 and GII.4 VLP IgM as Compared to Baseline
Run I was defined as the initial analysis performed once Day 56 post dose data was available. Run II was defined as final analysis performed after all later time points were achieved.
Measured: I run: 7, 21, 28 days PD1, 7 and 28 days PD2; II run: 28, 152 and 365 days PD2 (up to Day 393)
Percentage of Participants With Seroresponse for Serum Anti-norovirus GI.1 and GII.4 VLP IgA
Seroresponse was defined as a 4-fold increase in antibody titer compared to pre-immunization titers. Run I was defined as the initial analysis performed once Day 56 post dose data was available. Run II was defined as final analysis performed after all later time points were achieved.
Measured: I run: 7, 21, 28 days PD1, 7 and 28 days PD2; II run: 28, 152 and 365 days PD2 (up to Day 393)
Percentage of Participants With Seroresponse for Serum Anti-norovirus GI.1 and GII.4 VLP IgG
Seroresponse was defined as a 4-fold increase in antibody titer compared to pre-immunization titers. Run I was defined as the initial analysis performed once Day 56 post dose data was available. Run II was defined as final analysis performed after all later time points were achieved.
Measured: I run: 7, 21, 28 days PD1, 7 and 28 days PD2; II run: 28, 152 and 365 days PD2 (up to Day 393)
Percentage of Participants With Seroresponse for Serum Anti-norovirus GI.1 and GII.4 VLP IgM
Seroresponse was defined as a 4-fold increase in antibody titer compared to pre-immunization titers. Run I was defined as the initial analysis performed once Day 56 post dose data was available. Run II was defined as final analysis performed after all later time points were achieved.
Measured: I run: 7, 21, 28 days PD1, 7 and 28 days PD2; II run: 28, 152 and 365 days PD2 (up to Day 393)
GMT of Anti-norovirus GI.1 and GII.4 VLP IgA, IgG, and IgM Combined Using Pan-Ig Enzyme-Linked Immunosorbent Assay (ELISA)
GMTs were assessed for Anti-norovirus GI.1 and GII.4 VLP by Pan-Ig ELISA. A pan ELISA assay captured IgG, IgA and IgM combined. Run I was defined as the initial analysis performed once Day 56 post dose data was available. Run II was defined as final analysis performed after all later time points were achieved.
Measured: I run: predose 1, 7, 21, 28 days PD1, 7 and 28 days PD2; II run: predose 1, 28, 152 and 365 days PD2 (up to Day 393)
GMFR of Anti-norovirus GI.1 and GII.4 VLP IgA, IgG, and IgM Combined Using Pan-Ig ELISA as Compared to Baseline
GMFRs in GMTs of Anti-norovirus GI.1 and GII.4 VLP by Pan-Ig ELISA. A pan ELISA assay captured IgG, IgA and IgM combined. Run I was defined as the initial analysis performed once Day 56 post dose data was available. Run II was defined as final analysis performed after all later time points were achieved.
Measured: I run: 7, 21, 28 days PD1, 7 and 28 days PD2; II run: 28, 152 and 365 days PD2 (up to Day 393)
Percentage of Participants With Seroresponse (4-Fold Rise) of Anti-norovirus GI.1 and GII.4 VLP IgA, IgG, and IgM Combined Using Pan-Ig ELISA
Seroresponse was defined as a 4-fold increase in antibody titer compared to pre-immunization titers. Run I was defined as the initial analysis performed once Day 56 post dose data was available. Run II was defined as final analysis performed after all later time points were achieved.
Measured: I run: 7, 21, 28 days PD1, 7 and 28 days PD2; II run: 28, 152 and 365 days PD2 (up to Day 393)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

3 Sep 20109 Jan 2013

First posted23 Jul 2010 (estimated)
Study start3 Sep 2010
Primary completion1 Jan 2013
Study completion9 Jan 2013

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for GastroenteritisStudies of the same condition, open and under way.
More trials run by TakedaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 102 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01168401
Sponsor's protocol ID: LV03-104
Other IDs: U1111-1187-1052
Status last verified: Apr 2018
First submitted: 21 Jul 2010
Last updated: 23 Nov 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

Ramani S, Neill FH, Ferreira J, Treanor JJ, Frey SE, Topham DJ, Goodwin RR, Borkowski A, Baehner F, Mendelman PM, Estes MK, Atmar RL. B-Cell Responses to Intramuscular Administration of a Bivalent Virus-Like Particle Human Norovirus Vaccine. Clin Vaccine Immunol. 2017 May 5;24(5):e00571-16. doi: 10.1128/CVI.00571-16. Print 2017 May.
PubMed 28249841
Lindesmith LC, Ferris MT, Mullan CW, Ferreira J, Debbink K, Swanstrom J, Richardson C, Goodwin RR, Baehner F, Mendelman PM, Bargatze RF, Baric RS. Broad blockade antibody responses in human volunteers after immunization with a multivalent norovirus VLP candidate vaccine: immunological analyses from a phase I clinical trial. PLoS Med. 2015 Mar 24;12(3):e1001807. doi: 10.1371/journal.pmed.1001807. eCollection 2015 Mar.
PubMed 25803642
Treanor JJ, Atmar RL, Frey SE, Gormley R, Chen WH, Ferreira J, Goodwin R, Borkowski A, Clemens R, Mendelman PM. A novel intramuscular bivalent norovirus virus-like particle vaccine candidate--reactogenicity, safety, and immunogenicity in a phase 1 trial in healthy adults. J Infect Dis. 2014 Dec 1;210(11):1763-71. doi: 10.1093/infdis/jiu337. Epub 2014 Jun 20.
PubMed 24951828

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 23 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase 1, Randomized Controlled Dose Escalation, Safety and Immunogenicity Study of Intramuscular Norovirus GI.1/GII.4 Bivalent Virus-Like Particle (VLP) Vaccine Adjuvanted With Monophosphoryl Lipid A (MPL) and Aluminum Hydroxide [Al(OH)3] in Adults
ClinicalTrials.gov ID: NCT01168401
Acronym / sponsor ID: LV03-104
Conditions: Gastroenteritis
Keywords: Vaccine, norovirus, acute gastroenteritis
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 102 participants (actual)
Lead sponsor: TakedaIndustry (pharma, biotech, devices)
Study start: 3 Sep 2010 (actual)
Primary completion: 1 Jan 2013 (actual)
Study completion: 9 Jan 2013 (actual)
First posted: 23 Jul 2010 (estimated)
Results: Posted 23 Nov 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The hypotheses for this study are:

The incidence of adverse events after vaccination with IM Norovirus Bivalent VLP Vaccine will be similar to the incidence of adverse events after other IM vaccines including CERVARIX® which contains MPL and Al(OH)3.
Two doses of IM Norovirus Bivalent VLP Vaccine will be more immunogenic than one dose.
The post-vaccination serum antibody responses, the number of antibody secreting cells (ASC), including homing markers, and memory B-cell responses directed against norovirus antigens will be increased after IM Norovirus Bivalent VLP Vaccine compared to controls.

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2

Arm	Type	Receives
NoV GI.1/GII.4 Bivalent VLP Vaccine	Experimental	Biological: NoV GI.1/GII.4 Bivalent VLP VaccineNorovirus Bivalent GI.1 and GII.4 VLP Vaccine, adjuvanted with 50 microgram (mcg) MPL and 500 mcg Al(OH)3, IM, on Days 0 and 28.
Saline	Placebo comparator	Biological: Saline

Who may qualify

Ages: 18 to 85 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (14 listed)

Signed written informed consent.
Age:
Health Status:
Expressed interest and availability to fulfill the study requirements.
Female participants must be of non-childbearing potential (surgically sterile or post-menopausal for greater than or equal to [>=] 12 months), or if of childbearing potential (as determined by the investigator) must be practicing abstinence or using an effective licensed method of birth control (example oral contraceptives; diaphragm or condom in combination with contraceptive jelly, cream, or foam; intrauterine contraceptive device, or Depo-Provera; skin patch; vaginal ring or cervical cap) for 30 days prior to vaccination and must agree to continue such precautions for at least 60 days after the last vaccination. A woman is eligible if she is monogamous with a male who has had a vasectomy. Male participants must agree not to father a child for at least 60 days after the last vaccination and to practice abstinence or use an effective method of birth control as noted above.

Key exclusion criteria (40 listed)

Participants who meet any of the exclusion criteria at baseline will be excluded from study participation. The exclusion criteria are:
History of any of the following medical illnesses:
Any current illness requiring daily medication other than the following:
Allergies or hypersensitivity to any component of the vaccine including MPL and Al(OH)3 adjuvants.
Any clinically significant abnormality detected on physical examination, including:

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
NoV GI.1/GII.4 Bivalent VLP Vaccine2 Doses 28 days apart Cohort A: 18-49 Years Cohort A1: IM Norovirus Bivalent GI.1/GII.4 VLP Vaccine (5/5 mcg) Cohort A2: IM Norovirus Bivalent GI.1/GII.4 VLP Vaccine (15/15 mcg) Cohort A3: IM Norovirus Bivalent GI.1/GII.4 VLP Vaccine (50/50 mcg) Cohort A4: IM Norovirus Bivalent GI.1/GII.4 VLP Vaccine (150/150 mcg) Cohort B: 50-64 Years IM Norovirus Bivalent GI.1/GII.4 VLP Vaccine (50/50 mcg) Cohort C: 65-85 Years IM Norovirus Bivalent GI.1/GII.4 VLP Vaccine (50/50 mcg) Cohort D: 18-49 Years IM Norovirus Bivalent GI.1/GII.4 VLP Vaccine (50/50 mcg)	Biological	NoV GI.1/GII.4 Bivalent VLP Vaccine
SalineTwo doses 28 days apart	Biological	Saline

Primary outcome

Number of Participants With Solicited Local Adverse Events (AEs) Post Dose 1
Time frame: Day 0 up to Day 7
The solicited local adverse events were reported using a memory aid. Pain was scaled as Mild (did not interfere with activity); Moderate (repeated use of non-narcotic pain reliever greater than (>) 24 hours [24h] or interfered with activity); and Severe (any use of narcotic pain reliever or prevented daily activity). Tenderness was scaled as Mild (mild discomfort to touch); Moderate (discomfort with movement); and Severe (significant discomfort at rest). Swelling and redness were scaled as Mild (2.5-5 centimeter [cm] and did not interfere with activity); Moderate (5.1-10 cm or interfered with activity); and Severe (>10 cm or prevented daily activity).
Number of Participants With Solicited Local AEs Post Dose 2
Time frame: Day 28 up to Day 35
The solicited local adverse events were reported using a memory aid. Pain was scaled as Mild (did not interfered with activity); Moderate (repeated use of non-narcotic pain reliever >24h or interfered with activity); and Severe (any use of narcotic pain reliever or prevented daily activity). Tenderness was scaled as Mild (mild discomfort to touch); Moderate (discomfort with movement); and Severe (significant discomfort at rest). Swelling and redness were scaled as Mild (2.5-5 cm and did not interfere with activity); Moderate (5.1-10 cm or interfered with activity); and Severe (>10 cm or prevented daily activity).
Number of Participants With Solicited Systemic AEs Post Dose 1
Time frame: Day 0 up to Day 7
Elevated oral temperature:Mild(38-38.4 Celsius[C]);Moderate(38.5-38.9 C);Severe(39-40 C).Headache:Mild(no interference with activity);Moderate(repeated use of non-narcotic pain reliever>24h/some interference with activity);Severe(significant;any use of narcotic pain reliever/prevented daily activity).Fatigue,Malaise:Mild(no interference with activity);Moderate(some interference with activity);Severe(significant;prevented daily activity).Diarrhea:Mild(2-3loose stools/<400gram[g]/24h);Moderate(4-5stools/400-800g/24h);Severe(>=6watery stools/>800g/24h/required intravenous[IV]hydration).Nausea/Vomiting:Mild(no interference with activity/1-2 episodes/24h);Moderate(some interference with activity/>2 episodes/24h);Severe(prevented daily activity,required IV hydration).Muscle ache,chills,joint ache,abdominal cramp/pain:Mild(no interference with activity);Moderate(some interference with activity,not required medical intervention);Severe(prevented daily activity,required medical intervention).
Number of Participants With Solicited Systemic AEs Post Dose 2
Time frame: Day 28 up to Day 35
Elevated oral temperature:Mild(38-38.4 C);Moderate(38.5-38.9 C);Severe(39-40 C).Headache:Mild(no interference with activity);Moderate(repeated use of non-narcotic pain reliever>24h/some interference with activity);Severe(significant;any use of narcotic pain reliever/prevented daily activity).Fatigue,Malaise:Mild(no interference with activity);Moderate(some interference with activity);Severe(significant;prevented daily activity).Diarrhea:Mild(2-3loose stools/<400g/24h);Moderate(4-5stools/400-800g/24h);Severe(>=6watery stools/>800g/24h/required IV hydration).Nausea/Vomiting:Mild(no interference with activity/1-2 episodes/24h);Moderate(some interference with activity/>2 episodes/24h);Severe(prevented daily activity,required IV hydration).Muscle ache,chills,joint ache,abdominal cramp/pain:Mild(no interference with activity);Moderate(some interference with activity,not required medical intervention);Severe(prevented daily activity,required medical intervention).
Number of Participants With Unsolicited AEs Post Dose 1
Time frame: Baseline up to Day 28 (Pre-dose 2)
Number of Participants With Unsolicited AEs Post Dose 2
Time frame: Day 28 up to Day 56 (Post dose 2)
Number of Participants With Clinically Significant Change From Baseline in Markedly Abnormal Laboratory Values
Time frame: Baseline up to Day 35
The number of participants with any markedly abnormal standard safety laboratory values (serum chemistry or hematology) collected throughout study.
Number of Participants With Serious Adverse Events (SAEs), Onset of Significant New Medical Conditions, Including Adverse Events of Special Interest (AESI)
Time frame: Baseline up to 365 Days after post dose 2 (Day 393)

12 secondary outcomes

Geometric Mean Titer (GMT) of Serum Anti-norovirus GI.1 and GII.4 VLP Ig (Immunoglobulin) A
Time frame: First (I) run: predose 1 and 7, 21, 28 days postdose (PD)1, and 7 and 28 days PD2; second (II) run: predose 1 and 28, 152 and 365 days PD2 (up to Day 393)
GMT of Serum Anti-norovirus GI.1 and GII.4 VLP IgG
Time frame: I run: predose 1 and 7, 21, 28 days PD1, and 7 and 28 days PD2; II run: predose 1 and 28, 152 and 365 days PD2 (up to Day 393)
GMT of Serum Anti-norovirus GI.1 and GII.4 VLP IgM
Time frame: I run: predose 1 and 7, 21, 28 days PD1, and 7 and 28 days PD2; II run: predose 1 and 28, 152 and 365 days PD2 (up to Day 393)
Geometric Mean Fold Rise (GMFR) of Serum Anti-norovirus GI.1 and GII.4 VLP IgA as Compared to Baseline
Time frame: I run: 7, 21, 28 days PD1, 7 and 28 days PD2; II run: 28, 152 and 365 days PD2 (up to Day 393)
GMFR of Serum Anti-norovirus GI.1 and GII.4 VLP IgG as Compared to Baseline
Time frame: I run: 7, 21, 28 days PD1, 7 and 28 days PD2; II run: 28, 152 and 365 days PD2 (up to Day 393)
GMFR of Serum Anti-norovirus GI.1 and GII.4 VLP IgM as Compared to Baseline
Time frame: I run: 7, 21, 28 days PD1, 7 and 28 days PD2; II run: 28, 152 and 365 days PD2 (up to Day 393)
Percentage of Participants With Seroresponse for Serum Anti-norovirus GI.1 and GII.4 VLP IgA
Time frame: I run: 7, 21, 28 days PD1, 7 and 28 days PD2; II run: 28, 152 and 365 days PD2 (up to Day 393)
Percentage of Participants With Seroresponse for Serum Anti-norovirus GI.1 and GII.4 VLP IgG
Time frame: I run: 7, 21, 28 days PD1, 7 and 28 days PD2; II run: 28, 152 and 365 days PD2 (up to Day 393)
Percentage of Participants With Seroresponse for Serum Anti-norovirus GI.1 and GII.4 VLP IgM
Time frame: I run: 7, 21, 28 days PD1, 7 and 28 days PD2; II run: 28, 152 and 365 days PD2 (up to Day 393)
GMT of Anti-norovirus GI.1 and GII.4 VLP IgA, IgG, and IgM Combined Using Pan-Ig Enzyme-Linked Immunosorbent Assay (ELISA)
Time frame: I run: predose 1, 7, 21, 28 days PD1, 7 and 28 days PD2; II run: predose 1, 28, 152 and 365 days PD2 (up to Day 393)
GMFR of Anti-norovirus GI.1 and GII.4 VLP IgA, IgG, and IgM Combined Using Pan-Ig ELISA as Compared to Baseline
Time frame: I run: 7, 21, 28 days PD1, 7 and 28 days PD2; II run: 28, 152 and 365 days PD2 (up to Day 393)
Percentage of Participants With Seroresponse (4-Fold Rise) of Anti-norovirus GI.1 and GII.4 VLP IgA, IgG, and IgM Combined Using Pan-Ig ELISA
Time frame: I run: 7, 21, 28 days PD1, 7 and 28 days PD2; II run: 28, 152 and 365 days PD2 (up to Day 393)

Results and safety

Results posted to the registry on 23 Nov 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cohort A1: Norovirus Bivalent GI.1/GII.4 VLP Vaccine 5/5 mcg	10	9
Cohort A2:Norovirus Bivalent GI.1/GII.4 VLP Vaccine 15/15 mcg	10	9
Cohort A3: Norovirus Bivalent GI.1/GII.4 VLP Vaccine 50/50 mcg	10	8
Cohort A4:Norovirus Bivalent GI.1/GII.4 VLP Vaccine 150/150mcg	9	7
Cohort A1-A4: Placebo	9	9
Cohort B: Norovirus Bivalent GI.1/GII.4 VLP Vaccine 50/50 mcg	9	9
Cohort B: Placebo	10	10
Cohort C: Norovirus Bivalent GI.1/GII.4 VLP Vaccine 50/50 mcg	10	10
Cohort C: Placebo	9	9
Cohort D: Norovirus Bivalent VLP GI.1/GII.4 Vaccine 50/50 mcg	8	8
Cohort D: Placebo	8	8

Primary outcome: Number of Participants With Solicited Local Adverse Events (AEs) Post Dose 1

Time frame: Day 0 up to Day 7. Number. Unit: participants

Measure	Cohort A1: Norovirus Bivalent GI.1/GII.4 VLP Vaccine 5/5 mcg n = 10	Cohort A2: Norovirus Bivalent GI.1/GII.4 VLP Vaccine 15/15 mcg n = 10	Cohort A3: Norovirus Bivalent GI.1/GII.4 VLP Vaccine 50/50 mcg n = 10	Cohort A4:Norovirus Bivalent GI.1/GII.4 VLP Vaccine 150/150mcg n = 9	Cohort A1-A4: Placebo n = 9	Cohort B: Norovirus Bivalent GI.1/GII.4 VLP Vaccine 50/50 mcg n = 9	Cohort B: Placebo n = 10	Cohort C: Norovirus Bivalent GI.1/GII.4 VLP Vaccine 50/50 mcg n = 10	Cohort D: Norovirus Bivalent VLP GI.1/GII.4 Vaccine 50/50 mcg n = 8	Cohort D: Placebo n = 8
Pain: Mild	4	5	6	5	1	5	0	4	4	0
Pain: Moderate	4	2	2	2	0	2	0	0	0	0
Tenderness: Mild	4	5	6	5	1	4	1	6	3	2
Tenderness: Moderate	3	4	2	2	0	2	0	0	1	0
Swelling: Mild	1	2	2	1	0	1	1	1	3	3

Population analysed: mITT population included all participants who received at least 1 dose of study product. Only those categories have been reported below where at least 1 participant experienced the event.

Primary outcome: Number of Participants With Solicited Local AEs Post Dose 2

Time frame: Day 28 up to Day 35. Number. Unit: participants

Measure	Cohort A1: Norovirus Bivalent GI.1/GII.4 VLP Vaccine 5/5 mcg n = 9	Cohort A2: Norovirus Bivalent GI.1/GII.4 VLP Vaccine 15/15 mcg n = 7	Cohort A3: Norovirus Bivalent GI.1/GII.4 VLP Vaccine 50/50 mcg n = 10	Cohort A4:Norovirus Bivalent GI.1/GII.4 VLP Vaccine 150/150mcg n = 8	Cohort A1-A4: Placebo n = 8	Cohort B: Norovirus Bivalent GI.1/GII.4 VLP Vaccine 50/50 mcg n = 8	Cohort B: Placebo n = 10	Cohort C: Norovirus Bivalent GI.1/GII.4 VLP Vaccine 50/50 mcg n = 9	Cohort C: Placebo n = 9	Cohort D: Norovirus Bivalent VLP GI.1/GII.4 Vaccine 50/50 mcg n = 8	Cohort D: Placebo n = 7
Pain: Mild	5	4	4	2	0	3	0	5	0	3	1
Pain: Moderate	3	1	0	0	0	2	0	0	0	1	0
Tenderness: Mild	7	6	6	3	1	6	1	4	0	5	2
Tenderness: Moderate	1	1	0	0	0	1	0	0	0	0	0
Swelling: Mild	0	0	1	1	0	0	0	0	0	4	5
Swelling: Moderate	1	0	0	0	0	0	0	0	0	0	0
Redness: Mild	1

Primary outcome: Number of Participants With Solicited Systemic AEs Post Dose 1

Time frame: Day 0 up to Day 7. Number. Unit: participants

Measure	Cohort A1: Norovirus Bivalent GI.1/GII.4 VLP Vaccine 5/5 mcg n = 10	Cohort A2: Norovirus Bivalent GI.1/GII.4 VLP Vaccine 15/15 mcg n = 10	Cohort A3: Norovirus Bivalent GI.1/GII.4 VLP Vaccine 50/50 mcg n = 10	Cohort A4:Norovirus Bivalent GI.1/GII.4 VLP Vaccine 150/150mcg n = 9	Cohort A1-A4: Placebo n = 9	Cohort B: Norovirus Bivalent GI.1/GII.4 VLP Vaccine 50/50 mcg n = 9	Cohort B: Placebo n = 10	Cohort C: Norovirus Bivalent GI.1/GII.4 VLP Vaccine 50/50 mcg n = 10	Cohort C: Placebo n = 9	Cohort D: Norovirus Bivalent VLP GI.1/GII.4 Vaccine 50/50 mcg n = 8	Cohort D: Placebo n = 8
Headache: Mild	1	3	3	2	2	5	0	2	2	0	2
Headache: Moderate	3	1	0	1	0	0	0	0	0	0	1
Fatigue/ Malaise: Mild	1	1	1	1	0	2	1	0	0	0	1
Fatigue/ Malaise: Moderate	4	1	1	0	0	0	0	0	0	0	0
Muscle Aches : Mild	4	2	1	3	1	0	0	0	0	0	0
Muscle Aches : Moderate	1	0	1	0	0	0	0	1	0	0	0
Joint Aches: Mild

Primary outcome: Number of Participants With Solicited Systemic AEs Post Dose 2

Time frame: Day 28 up to Day 35. Number. Unit: participants

Measure	Cohort A1: Norovirus Bivalent GI.1/GII.4 VLP Vaccine 5/5 mcg n = 9	Cohort A2: Norovirus Bivalent GI.1/GII.4 VLP Vaccine 15/15 mcg n = 7	Cohort A3: Norovirus Bivalent GI.1/GII.4 VLP Vaccine 50/50 mcg n = 10	Cohort A4:Norovirus Bivalent GI.1/GII.4 VLP Vaccine 150/150mcg n = 8	Cohort A1-A4: Placebo n = 8	Cohort B: Norovirus Bivalent GI.1/GII.4 VLP Vaccine 50/50 mcg n = 8	Cohort B: Placebo n = 10	Cohort C: Norovirus Bivalent GI.1/GII.4 VLP Vaccine 50/50 mcg n = 9	Cohort C: Placebo n = 9	Cohort D: Norovirus Bivalent VLP GI.1/GII.4 Vaccine 50/50 mcg n = 8	Cohort D: Placebo n = 7
Headache: Mild	1	1	3	2	1	3	0	1	1	1	1
Headache: Moderate	2	0	1	0	0	0	0	0	0	0	1
Headache: Severe	0	0	0	0	0	0	0	1	0	0	0
Fatigue/ Malaise: Mild	1	0	3	0	1	2	0	0	0	0	0
Fatigue/ Malaise: Moderate	2	0	0	0	0	0	0	0	0	0	1
Muscle Aches: Mild	2	1	3	1	0	0	0	0	0	0	0
Muscle Aches: Moderate

12 secondary outcomes are reported in the full results.

Adverse events

Time frame: Treatment-emergent adverse events are adverse events that started after the first dose of study drug and up to 365 Days after post dose 2 (Day 393). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cohort A1: Norovirus Bivalent GI.1/GII.4 VLP Vaccine 5/5 mcg	1 of 10 (10%)	8 of 10 (80%)	Not reported
Cohort A2: Norovirus Bivalent GI.1/GII.4 VLP Vaccine 15/15 mcg	0 of 10 (0%)	5 of 10 (50%)	Not reported
Cohort A3: Norovirus Bivalent GI.1/GII.4 VLP Vaccine 50/50 mcg	1 of 10 (10%)	5 of 10 (50%)	Not reported
Cohort A4:Norovirus Bivalent GI.1/GII.4 VLP Vaccine 150/150mcg	0 of 9 (0%)	3 of 9 (33.3%)	Not reported
Cohort A1-A4: Placebo	0 of 9 (0%)	3 of 9 (33.3%)	Not reported
Cohort B: Norovirus Bivalent GI.1/GII.4 VLP Vaccine 50/50 mcg	0 of 9 (0%)	5 of 9 (55.6%)	Not reported
Cohort B: Placebo	1 of 10 (10%)	3 of 10 (30%)	Not reported
Cohort C: Norovirus Bivalent GI.1/GII.4 VLP Vaccine 50/50 mcg	2 of 10 (20%)	4 of 10 (40%)	Not reported
Cohort C: Placebo	0 of 9 (0%)	5 of 9 (55.6%)	Not reported
Cohort D: Norovirus Bivalent VLP GI.1/GII.4 Vaccine 50/50 mcg	0 of 8 (0%)	5 of 8 (62.5%)	Not reported
Cohort D: Placebo	0 of 8 (0%)	5 of 8 (62.5%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Nov 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 28249841Ramani S, Neill FH, Ferreira J, Treanor JJ, Frey SE, Topham DJ, Goodwin RR, Borkowski A, Baehner F, Mendelman PM, Estes MK, Atmar RL. B-Cell Responses to Intramuscular Administration of a Bivalent Virus-Like Particle Human Norovirus Vaccine. Clin Vaccine Immunol. 2017 May 5;24(5):e00571-16. doi: 10.1128/CVI.00571-16. Print 2017 May.
Derived from this study: PubMed 25803642Lindesmith LC, Ferris MT, Mullan CW, Ferreira J, Debbink K, Swanstrom J, Richardson C, Goodwin RR, Baehner F, Mendelman PM, Bargatze RF, Baric RS. Broad blockade antibody responses in human volunteers after immunization with a multivalent norovirus VLP candidate vaccine: immunological analyses from a phase I clinical trial. PLoS Med. 2015 Mar 24;12(3):e1001807. doi: 10.1371/journal.pmed.1001807. eCollection 2015 Mar.
Derived from this study: PubMed 24951828Treanor JJ, Atmar RL, Frey SE, Gormley R, Chen WH, Ferreira J, Goodwin R, Borkowski A, Clemens R, Mendelman PM. A novel intramuscular bivalent norovirus virus-like particle vaccine candidate--reactogenicity, safety, and immunogenicity in a phase 1 trial in healthy adults. J Infect Dis. 2014 Dec 1;210(11):1763-71. doi: 10.1093/infdis/jiu337. Epub 2014 Jun 20.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing NoV GI.1/GII.4 Bivalent VLP Vaccine and Saline in people with Gastroenteritis, run by Takeda at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 40 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Nov 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Solicited Local Adverse Events (AEs) Post Dose 1 (time frame: Day 0 up to Day 7). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01168401, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Nov 2018.