Norovirus PreventionPhase 2NCT02142504
Safety and Immunogenicity of Norovirus Bivalent Virus-Like Particle Vaccine in Healthy Adults
A Phase 2 study testing Norovirus Bivalent VLP Vaccine in people with Norovirus Prevention, run by Takeda at 10 sites in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 49 yearsHealthy volunteers can take part
- Conditions the study is for
- Norovirus Prevention
- What is being tested?
- Norovirus Bivalent VLP Vaccine
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 454 participants
- Where
- 10 sitesUnited States
- Study dates
- 15 May 2014to 6 Jan 2016
- Phase
- Phase 2
- 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 49 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male and female participants aged 18 to 49 years of age at the time of enrollment.
- Are in good health at the time of entry into the trial as determined by medical history, physical examination and clinical judgment of the investigator.
- Participants with a signed informed consent form and any required privacy authorization prior to the initiation of any trial procedures and after the nature of the trial has been explained according to local regulatory requirements.
- Can comply with trial procedures and are available for the duration of the trial.
Who cannot join
- Has a history of acute gastroenteritis within 14 days of enrollment.
- Has a clinically significant active infection (as assessed by the investigator) or oral body temperature 38°C (100.4°F) or higher within 3 days of the intended date of vaccination.
- Has received antipyretic/analgesic medications within 24 hours prior to the intended vaccine administration.
- Has known hypersensitivity or allergy to any of the bivalent norovirus virus-like particle (VLP) vaccine components (including excipients of the investigational vaccines).
- Has 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.
- Has a history of any progressive or severe neurologic disorder, seizure disorder, or neuro-inflammatory disease (e.g., Guillain-Barré syndrome).
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- Has history or any illness that, in the opinion of the investigator, might interfere with the results of the trial or pose additional risk to the participants due to participation in the trial.
- Has known or suspected impairment/alteration of immune function including the following:
- Chronic use of oral steroids (Equivalent to 20 mg/day prednisone for ≥ 12 weeks / ≥2 mg/kg body weight /day for ≥ 2 weeks) within 60 days prior to Day 1 (use of inhaled, intranasal, or topical corticosteroids is allowed).
- Receipt of parenteral steroids (equivalent to 20 mg/day prednisone ≥ 12 weeks / ≥2 mg/kg body weight /day for ≥2 weeks) within 60 days prior to Day 1.
- Receipt of immunostimulants within 60 days prior to Day 1.
- Receipt of parenteral, epidural, or intra-articular immunoglobulin preparation, blood products, and/or plasma derivatives within 3 months prior to Day 1 or planned during the full length of the trial.
- Receipt of immunosuppressive therapy within 6 months prior to Day 1.
- Human immunodeficiency virus (HIV) infection or HIV-related disease.
- Heritable immunodeficiency.
- Has abnormalities of splenic or thymic function.
- Has a history of any autoimmune disease.
- Has a known bleeding diathesis or any condition that may be associated with a prolonged bleeding time.
- Has any serious chronic or progressive disease according to judgment of the investigator (e.g., neoplasm, insulin dependent diabetes, cardiac, renal, or hepatic disease).
- Has a body mass index (BMI) greater than or equal to 35 kg/m^2 (= weight in kg / [height in meters * height in meters]).
- Is participating in any clinical trial with another investigational product 30 days prior to first trial visit or intent to participate in another clinical trial at any time during the conduct of this trial.
- Participants who received any inactivated vaccines within 14 days or any live vaccines for 28 days prior to enrollment in this trial.
- Are first degree relatives of individuals involved in trial conduct.
- Has a history of substance or alcohol abuse within the past 2 years.
- If female, "of childbearing potential", sexually active, and has not used any of the "acceptable contraceptive methods" for at least 2 months prior to trial entry:
- Of childbearing potential is defined as status post onset of menarche and not meeting any of the following conditions: menopausal for at least 2 years, status after bilateral tubal ligation for at least 1 year, status after bilateral oophorectomy, or status after hysterectomy.
- Acceptable birth control methods are defined as 1 or more of the following:
- Hormonal contraceptive (such as oral, injection, transdermal patch, implant, cervical ring).
- Barrier (condom with spermicide or diaphragm with spermicide) each and every time during intercourse.
- Intrauterine device (IUD). iv. Monogamous relationship with vasectomized partner. Partner must have been vasectomized for at least 6 months prior to the participant's trial entry.
- Female participants of childbearing potential and sexually active, who refuse to use an "acceptable contraceptive method" from Day 1 through 6 months after the last dose of investigational vaccine.
- Female participants who plan to donate ova from Day 1 through 6 months after the last dose of investigational vaccine.
- Female participants with any positive pregnancy test.
- Female participants who are pregnant or breastfeeding.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Benchmark Research Austin
Austin, Texas, 78705
SNBL
Baltimore, Maryland, 21201
Cincinnati Childrens Hospital Medical Center
Cincinnati, Ohio, 45206
Clin Research of South Florida
Coral Gables, Florida, 33134
Baylor College of Medicine
Houston, Texas, 77030-3498
Rochester Clinical Research
Rochester, New York, 14609
University of Rochester
Rochester, New York, 14642
California Research Foundation
San Diego, California, 92103-6204
Benchmark Research San Francisco
San Francisco, California, 94108
St. Louis University, School of Medicine
St Louis, Missouri, 63104
About this study
Official title: Phase II, Randomized, Placebo-controlled, Double-blind, Safety and Immunogenicity Trial of Intramuscular Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine in Healthy Adults
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.
Read the detailed description
The vaccine being tested in this study is called norovirus GI.1/GII.4 bivalent virus-like particle (VLP) vaccine adjuvanted with or without monophosphoryl lipid A (MPL) and with aluminum hydroxide. The norovirus vaccine is being tested to provide additional safety and immunogenicity data to enable the vaccine to be further developed. This study will look at the side effects in people who take different formulations of the norovirus vaccine.
The study will enroll approximately 450 participants. Participants will be randomly assigned (by chance, like flipping a coin) to one of the 3 treatment groups-which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):
- one dose of GI.1/GII.4 (15 µg/50 µg) adjuvanted with MPL (50 µg) and aluminum hydroxide (500 µg) on Day 1 followed by one dose of GI.1/GII.4 (15 µg/15 µg) adjuvanted with aluminum hydroxide (500 µg) (without MPL) on Day 365
- one dose of GI.1/GII.4 (50 µg/50 µg) adjuvanted with MPL (50 µg) and aluminum hydroxide (500 µg) on Day 1 followed by one dose of GI.1/GII.4 (15 µg/15 µg) adjuvanted with aluminum hydroxide (500 µg) (without MPL) on Day 365
- one dose of Saline Placebo (dummy inactive injection) - this is a liquid that has no active ingredient-on Day 1 + GI.1/GII.4 (15 µg/15 µg) adjuvanted with aluminum hydroxide (500 µg) (without MPL) as primary vaccination on Day 365
All participants will be administered vaccine or placebo on Day 1 of the study and will receive a vaccination dose (reduced antigen content) of the norovirus vaccine on Day 365. Participants will be asked to record any symptoms that may be related to the vaccine or the injection site in a diary card for 7 days after each vaccination.
This multi-center trial will be conducted in the United States. The overall time to participate in this study is up to 18 months. Participants will make 11 visits to the clinic including a follow-up visit 6 months after the last dose of study medication.
- Conditions
- Norovirus Prevention
- Being tested
- Norovirus Bivalent VLP Vaccine, Placebo (Saline)
- Keywords
- Drug therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Norovirus Bivalent VLP VaccineBiological
Norovirus GI.1/GII.4 bivalent VLP vaccine adjuvanted with or without MPL and/or aluminum hydroxide IM injection
Placebo (Saline)Drug
Placebo-matching norovirus bivalent VLP vaccine
| Study group | Role | What they receive |
|---|---|---|
| GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL) | Experimental | Intramuscular (IM) norovirus bivalent virus like particle (VLP) vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg monophosphoryl lipid A (MPL) and 500 µg aluminum hydroxide, on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide (no MPL), on Day 365. Receives: Biological: Norovirus Bivalent VLP Vaccine |
| GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL) | Experimental | IM norovirus bivalent VLP vaccine (50 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg monophosphoryl lipid A (MPL) and 500 µg aluminum hydroxide, on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide (no MPL), on Day 365. Receives: Biological: Norovirus Bivalent VLP Vaccine |
| Saline Placebo + GI.1/GII.4 15/15 μg (No MPL) | Placebo comparator | IM saline placebo on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP ) adjuvanted with 500 µg aluminum hydroxide (no MPL), on Day 365. Receives: Biological: Norovirus Bivalent VLP Vaccine; Drug: Placebo (Saline) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Solicited Local Adverse Events (AEs) at Injection Site After the First Injection
Solicited local AEs at injection site are defined as: pain, erythema, induration, and swelling that occurred within 7 days after the primary injection.
Measured: Days 1 through 7
Percentage of Participants With Solicited Systemic Adverse Events (AEs) After the First Injection
Solicited systemic AEs are defined as: headache, fatigue, myalgia, arthralgia, vomiting, and diarrhea that occurred within 7 days after the primary injection.
Measured: Days 1 through 7
Percentage of Participants With Elevated Daily Oral Temperature (Fever) After the First Injection
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.
Measured: Days 1 through 7
Percentage of Participants With Unsolicited Adverse Events (AEs) After the First Injection
Unsolicited AEs are any AEs that are not solicited local or systemic AEs, as defined by this study.
Measured: Days 1 through 28
Percentage of Participants With Serious Adverse Events (SAEs) After the First Injection
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.
Measured: From first injection (Day 1) to second injection pre-dose (Up to Day 365)
Percentage of Participants With Serious Adverse Events (SAEs) After the Second Injection
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.
Measured: From second injection (Day 365) to 6 months after second injection (Up to Day 545)
Percentage of Participants With Adverse Events of Special Interest (AESI) After the First Injection
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.
Measured: From first injection (Day 1) to second injection pre-dose (Up to Day 365)
Percentage of Participants With Adverse Events of Special Interest (AESI) After the Second Injection
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.
Measured: From second injection (Day 365) to 6 months after second injection (Up to Day 545)
Percentage of Participants With Any Adverse Event (AE) Leading to Withdrawal From the Study
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.
Measured: 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)
Secondary outcomes (18)
Percentage of Participants With Solicited Local Adverse Events (AEs) at Injection Site After the Second Injection
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.
Measured: Days 365 through 371
Percentage of Participants With Solicited Systemic Adverse Events (AEs) After the Second Injection
Solicited systemic AEs are defined as: headache, fatigue, myalgia, arthralgia, vomiting, and diarrhea that occurred within 7 days after the vaccination on Day 365.
Measured: Days 365 through 371
Percentage of Participants With Elevated Daily Oral Temperature (Fever) After the Second Injection
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.
Measured: Days 365 through 371
Percentage of Participants With Unsolicited Adverse Events (AEs) After the Second Injection
Unsolicited AEs are any AEs that are not solicited local or systemic AEs, as defined by this study.
Measured: Days 365 through 393
Percentage of Participants With a Seroresponse in Both Serum Anti-norovirus GI.1 VLP and GII.4 VLP (Pan-Ig ELISA)
Seroresponse is defined as 4-fold rise or greater in serum anti-norovirus antibody titers for both GI.1 virus-Like particle (VLP) and GII.4 VLP as measured by pan immunoglobulin (Pan-Ig) enzyme-linked immunosorbent assay (ELISA).
Measured: Baseline and Day 28
Percentage of Participants With a Seroresponse in Serum Anti-norovirus GI.1 VLP (Pan-Ig ELISA)
Seroresponse is defined as 4-fold rise or greater in serum anti-norovirus antibody titers for GI.1 virus-Like particle (VLP) as measured by pan immunoglobulin (Pan-Ig) enzyme-linked immunosorbent assay (ELISA).
Measured: Baseline and Day 28
Percentage of Participants With a Seroresponse in Serum Anti-norovirus GII.4 VLP (Pan-Ig ELISA)
Seroresponse is defined as 4-fold rise or greater in serum anti-norovirus antibody titers for GII.4 virus-like particles (VLP) as measured by pan immunoglobulin (Pan-Ig) enzyme-linked immunosorbent assay (ELISA).
Measured: Baseline and Day 28
Geometric Mean Titer (GMT) of GI.1 VLP Antibody Titers (Pan-Ig ELISA)
Geometric mean titer (GMT) of anti-norovirus GI.1 VLP antibody titers as measured by Pan-Ig ELISA.
Measured: Day 28
Geometric Mean Titer (GMT) of GII.4 VLP Antibody Titers (Pan-Ig ELISA)
Geometric mean titer (GMT) of anti-norovirus GII.4 VLP antibody titers as measured by Pan-Ig ELISA.
Measured: Day 28
Geometric Mean Fold Rise (GMFR) of GI.1 VLP Antibody Titers (Pan-Ig ELISA)
Geometric mean fold rise (GMFR) of anti-norovirus GI.1 VLP antibody titers as measured by Pan-Ig ELISA.
Measured: Day 28
Geometric Mean Fold Rise (GMFR) of GII.4 VLP Antibody Titers (Pan-Ig ELISA)
Geometric mean fold rise (GMFR) of anti-norovirus GII.4 VLP antibody titers as measured by Pan-Ig ELISA.
Measured: Day 28
Percentage of Participants With a Seroresponse in Both Serum Anti-norovirus GI.1 VLP and GII.4 VLP (HBGA)
Seroresponse is defined as 4-fold rise or greater in serum anti-norovirus antibody titers for both GI.1 virus-Like particle (VLP) and GII.4 VLP as measured by histoblood group antigen (HBGA) binding assay.
Measured: Baseline and Day 28
Percentage of Participants With a Seroresponse in Serum GI.1 VLP Antibody Titers (HBGA)
Seroresponse is defined as 4-fold rise or greater in serum anti-norovirus antibody titers for GI.1 virus-Like particle (VLP) as measured by HBGA binding assay.
Measured: Baseline and Day 28
Percentage of Participants With a Seroresponse in Serum GII.4 VLP Antibody Titers (HBGA)
Seroresponse is defined as 4-fold rise or greater in serum anti-norovirus antibody titers for GII.4 virus-Like particle (VLP) as measured by HBGA binding assay.
Measured: Baseline and Day 28
Blocking Titers 50 (BT50) of Anti-Norovirus GI.1 VLP Antibody Titers (HBGA)
Blocking titers 50 (BT50) of anti-norovirus GI.1 VLP antibody titers as measured by HBGA binding assay.
Measured: Day 28
Blocking Titers 50 (BT50) of Anti-Norovirus GII.4 VLP Antibody Titers (HBGA)
Blocking titers 50 (BT50) of anti-norovirus GII.4 VLP antibody titers as measured by HBGA binding assay.
Measured: Day 28
Geometric Mean Fold Rise (GMFR) of GI.1 VLP Antibody Titers (HBGA)
Geometric mean fold rise (GMFR) of anti-norovirus GI.1 VLP antibody titers as measured by HBGA binding assay.
Measured: Day 28
Geometric Mean Fold Rise (GMFR) of GII.4 VLP Antibody Titers (HBGA)
Geometric mean fold rise (GMFR) of anti-norovirus GII.4 VLP antibody titers as measured by the HBGA binding assay.
Measured: Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2014 (estimated)
- Study start15 May 2014
- Primary completion6 Jan 2016
- Study completion6 Jan 2016
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 (2)Papers the sponsor has linked to this study.
- Other trials for Norovirus PreventionStudies 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 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 454 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director Clinical Science, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02142504
- Sponsor's protocol ID
- NOR-201
- Other IDs
- U1111-1155-8803
- Status last verified
- Aug 2017
- First submitted
- 9 May 2014
- Last updated
- 21 Aug 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Atmar RL, Baehner F, Cramer JP, Lloyd E, Sherwood J, Borkowski A, Mendelman PM; NOR-201 Study Group. Persistence of Antibodies to 2 Virus-Like Particle Norovirus Vaccine Candidate Formulations in Healthy Adults: 1-Year Follow-up With Memory Probe Vaccination. J Infect Dis. 2019 Jul 19;220(4):603-614. doi: 10.1093/infdis/jiz170.
PubMed 31001633Atmar RL, Baehner F, Cramer JP, Song E, Borkowski A, Mendelman PM; NOR-201 Study Group. Rapid Responses to 2 Virus-Like Particle Norovirus Vaccine Candidate Formulations in Healthy Adults: A Randomized Controlled Trial. J Infect Dis. 2016 Sep 15;214(6):845-53. doi: 10.1093/infdis/jiw259. Epub 2016 Jun 28.
PubMed 27354368
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II, Randomized, Placebo-controlled, Double-blind, Safety and Immunogenicity Trial of Intramuscular Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine in Healthy Adults
- ClinicalTrials.gov ID
- NCT02142504
- Acronym / sponsor ID
- NOR-201
- Conditions
- Norovirus Prevention
- Keywords
- Drug therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 454 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- 15 May 2014 (actual)
- Primary completion
- 6 Jan 2016 (actual)
- Study completion
- 6 Jan 2016 (actual)
- First posted
- 20 May 2014 (estimated)
- Results
- Posted 23 Feb 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The vaccine being tested in this study is called norovirus GI.1/GII.4 bivalent virus-like particle (VLP) vaccine adjuvanted with or without monophosphoryl lipid A (MPL) and with aluminum hydroxide. The norovirus vaccine is being tested to provide additional safety and immunogenicity data to enable the vaccine to be further developed. This study will look at the side effects in people who take different formulations of the norovirus vaccine.
The study will enroll approximately 450 participants. Participants will be randomly assigned (by chance, like flipping a coin) to one of the 3 treatment groups-which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):
- one dose of GI.1/GII.4 (15 µg/50 µg) adjuvanted with MPL (50 µg) and aluminum hydroxide (500 µg) on Day 1 followed by one dose of GI.1/GII.4 (15 µg/15 µg) adjuvanted with aluminum hydroxide (500 µg) (without MPL) on Day 365
- one dose of GI.1/GII.4 (50 µg/50 µg) adjuvanted with MPL (50 µg) and aluminum hydroxide (500 µg) on Day 1 followed by one dose of GI.1/GII.4 (15 µg/15 µg) adjuvanted with aluminum hydroxide (500 µg) (without MPL) on Day 365
- one dose of Saline Placebo (dummy inactive injection) - this is a liquid that has no active ingredient-on Day 1 + GI.1/GII.4 (15 µg/15 µg) adjuvanted with aluminum hydroxide (500 µg) (without MPL) as primary vaccination on Day 365
All participants will be administered vaccine or placebo on Day 1 of the study and will receive a vaccination dose (reduced antigen content) of the norovirus vaccine on Day 365. Participants will be asked to record any symptoms that may be related to the vaccine or the injection site in a diary card for 7 days after each vaccination.
This multi-center trial will be conducted in the United States. The overall time to participate in this study is up to 18 months. Participants will make 11 visits to the clinic including a follow-up visit 6 months after the last dose of study medication.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL) | Experimental | Biological: Norovirus Bivalent VLP VaccineIntramuscular (IM) norovirus bivalent virus like particle (VLP) vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg monophosphoryl lipid A (MPL) and 500 µg aluminum hydroxide, on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide (no MPL), on Day 365. |
| GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL) | Experimental | Biological: Norovirus Bivalent VLP VaccineIM norovirus bivalent VLP vaccine (50 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg monophosphoryl lipid A (MPL) and 500 µg aluminum hydroxide, on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide (no MPL), on Day 365. |
| Saline Placebo + GI.1/GII.4 15/15 μg (No MPL) | Placebo comparator | Biological: Norovirus Bivalent VLP Vaccine, Drug: Placebo (Saline)IM saline placebo on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP ) adjuvanted with 500 µg aluminum hydroxide (no MPL), on Day 365. |
Who may qualify
- Ages
- 18 to 49 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Male and female participants aged 18 to 49 years of age at the time of enrollment.
- Are in good health at the time of entry into the trial as determined by medical history, physical examination and clinical judgment of the investigator.
- Participants with a signed informed consent form and any required privacy authorization prior to the initiation of any trial procedures and after the nature of the trial has been explained according to local regulatory requirements.
- Can comply with trial procedures and are available for the duration of the trial.
Key exclusion criteria (34 listed)
- Has a history of acute gastroenteritis within 14 days of enrollment.
- Has a clinically significant active infection (as assessed by the investigator) or oral body temperature 38°C (100.4°F) or higher within 3 days of the intended date of vaccination.
- Has received antipyretic/analgesic medications within 24 hours prior to the intended vaccine administration.
- Has known hypersensitivity or allergy to any of the bivalent norovirus virus-like particle (VLP) vaccine components (including excipients of the investigational vaccines).
- Has 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.
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 |
|---|---|---|
| Norovirus Bivalent VLP VaccineNorovirus GI.1/GII.4 bivalent VLP vaccine adjuvanted with or without MPL and/or aluminum hydroxide IM injection | Biological | GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL), GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL), Saline Placebo + GI.1/GII.4 15/15 μg (No MPL) |
| Placebo (Saline)Placebo-matching norovirus bivalent VLP vaccine | Drug | Saline Placebo + GI.1/GII.4 15/15 μg (No MPL) |
Primary outcome
Percentage of Participants With Solicited Local Adverse Events (AEs) at Injection Site After the First Injection
Time frame: 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.
Percentage of Participants With Solicited Systemic Adverse Events (AEs) After the First Injection
Time frame: 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.
Percentage of Participants With Elevated Daily Oral Temperature (Fever) After the First Injection
Time frame: 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.
Percentage of Participants With Unsolicited Adverse Events (AEs) After the First Injection
Time frame: Days 1 through 28
Unsolicited AEs are any AEs that are not solicited local or systemic AEs, as defined by this study.
Percentage of Participants With Serious Adverse Events (SAEs) After the First Injection
Time frame: 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.
Percentage of Participants With Serious Adverse Events (SAEs) After the Second Injection
Time frame: 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.
Percentage of Participants With Adverse Events of Special Interest (AESI) After the First Injection
Time frame: 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.
Percentage of Participants With Adverse Events of Special Interest (AESI) After the Second Injection
Time frame: 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.
Percentage of Participants With Any Adverse Event (AE) Leading to Withdrawal From the Study
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)
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.
18 secondary outcomes
Percentage of Participants With Solicited Local Adverse Events (AEs) at Injection Site After the Second Injection
Time frame: Days 365 through 371
Percentage of Participants With Solicited Systemic Adverse Events (AEs) After the Second Injection
Time frame: Days 365 through 371
Percentage of Participants With Elevated Daily Oral Temperature (Fever) After the Second Injection
Time frame: Days 365 through 371
Percentage of Participants With Unsolicited Adverse Events (AEs) After the Second Injection
Time frame: Days 365 through 393
Percentage of Participants With a Seroresponse in Both Serum Anti-norovirus GI.1 VLP and GII.4 VLP (Pan-Ig ELISA)
Time frame: Baseline and Day 28
Percentage of Participants With a Seroresponse in Serum Anti-norovirus GI.1 VLP (Pan-Ig ELISA)
Time frame: Baseline and Day 28
Percentage of Participants With a Seroresponse in Serum Anti-norovirus GII.4 VLP (Pan-Ig ELISA)
Time frame: Baseline and Day 28
Geometric Mean Titer (GMT) of GI.1 VLP Antibody Titers (Pan-Ig ELISA)
Time frame: Day 28
Geometric Mean Titer (GMT) of GII.4 VLP Antibody Titers (Pan-Ig ELISA)
Time frame: Day 28
Geometric Mean Fold Rise (GMFR) of GI.1 VLP Antibody Titers (Pan-Ig ELISA)
Time frame: Day 28
Geometric Mean Fold Rise (GMFR) of GII.4 VLP Antibody Titers (Pan-Ig ELISA)
Time frame: Day 28
Percentage of Participants With a Seroresponse in Both Serum Anti-norovirus GI.1 VLP and GII.4 VLP (HBGA)
Time frame: Baseline and Day 28
Percentage of Participants With a Seroresponse in Serum GI.1 VLP Antibody Titers (HBGA)
Time frame: Baseline and Day 28
Percentage of Participants With a Seroresponse in Serum GII.4 VLP Antibody Titers (HBGA)
Time frame: Baseline and Day 28
Blocking Titers 50 (BT50) of Anti-Norovirus GI.1 VLP Antibody Titers (HBGA)
Time frame: Day 28
Blocking Titers 50 (BT50) of Anti-Norovirus GII.4 VLP Antibody Titers (HBGA)
Time frame: Day 28
Geometric Mean Fold Rise (GMFR) of GI.1 VLP Antibody Titers (HBGA)
Time frame: Day 28
Geometric Mean Fold Rise (GMFR) of GII.4 VLP Antibody Titers (HBGA)
Time frame: Day 28
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31001633Atmar RL, Baehner F, Cramer JP, Lloyd E, Sherwood J, Borkowski A, Mendelman PM; NOR-201 Study Group. Persistence of Antibodies to 2 Virus-Like Particle Norovirus Vaccine Candidate Formulations in Healthy Adults: 1-Year Follow-up With Memory Probe Vaccination. J Infect Dis. 2019 Jul 19;220(4):603-614. doi: 10.1093/infdis/jiz170.
- Derived from this study: PubMed 27354368Atmar RL, Baehner F, Cramer JP, Song E, Borkowski A, Mendelman PM; NOR-201 Study Group. Rapid Responses to 2 Virus-Like Particle Norovirus Vaccine Candidate Formulations in Healthy Adults: A Randomized Controlled Trial. J Infect Dis. 2016 Sep 15;214(6):845-53. doi: 10.1093/infdis/jiw259. Epub 2016 Jun 28.
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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.
Medical Director Clinical Science study director
Takeda
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Norovirus Bivalent VLP Vaccine in people with Norovirus Prevention, run by Takeda at 10 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 4 inclusion and 34 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 21 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Feb 2017). 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?
Percentage of Participants With Solicited Local Adverse Events (AEs) at Injection Site After the First Injection (time frame: Days 1 through 7). The study lists 9 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 NCT02142504, which also lists 2 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 21 Aug 2017.