Healthy Volunteers
Conditions
Keywords
Drug therapy
Brief summary
The purpose of this study is to evaluate the efficacy of the Norovirus (NoV) GI.1/GII.4 bivalent virus-like particle vaccine against moderate or severe acute gastroenteritis (AGE) due to genotype-specific (GI.1 and GII.4) NoV strains.
Detailed description
The vaccine being tested in this study is called NoV GI.1/GII.4 bivalent VLP vaccine adjuvanted with aluminum hydroxide. The norovirus vaccine is being tested to prevent AGE due to genotype-specific (GI.1 and GII.4) norovirus strains in healthy participants recruited from a US military training installation. This study will look at the illness rate of AGE occurring \> 7 days after dosing due to genotype-specific (GI.1 or GII.4) NoV strains represented in the vaccine. The study will enroll between 2800 and 8700 patients. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups-which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need): * Norovirus GI.1/GII.4 Bivalent VLP Vaccine * Placebo (dummy inactive solution) - this is a liquid that looks similar to the study drug but has no active ingredient All participants will receive one dose of study medication on Day 1 administered via intramuscular injection. This multi-center trial will be conducted in the United States at select military locations. The overall time to participate in this study is up to 45 days for participants in the navy 53 days for participants in the Air Force, and 72 days for participants in the marines. Participants will make multiple visits to the clinic, including a final visit on the last day of study participation (Day 45, 53 or 72) for a follow-up assessment.
Interventions
BIOLOGICALNoV Placebo-matching Saline
NoV placebo-matching saline (0.9% sodium chloride).
BIOLOGICALNoV GI.1/GII.4 Bivalent VLP Vaccine
NoV bivalent VLP vaccine, adjuvanted with 500 µg aluminum as Al(OH)3.
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 49 Years
Healthy volunteers
Yes
Inclusion criteria
1. Participant signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any trial procedures after the nature of the trial has been explained according to local regulatory requirements. 2. Male or female participants, 18 to 49 years of age. 3. Is in good health at the time of entry into the trial as determined by medical history and the clinical judgment of the investigator. 4. Can comply with trial procedures and are available for the duration of follow-up.
Exclusion criteria
1. Pregnancy. 2. Has known hypersensitivity to any of the Norovirus (NoV) GI.1/GII.4 bivalent virus-like particle (VLP) vaccine components (including excipients). 3. Has known hypersensitivity or allergy to any of the licensed required concomitant vaccine components to be administered (including excipients of these vaccines). 4. Has any condition or circumstance that the investigator determines would interfere with trial evaluation or interpretation. 5. Has known or suspected impairment or alteration of immune function. 6. Has a history of acute gastroenteritis (AGE) within 14 days of enrollment. 7. Has a history of body temperature of 38.0°C (100.4°F) or higher within 3 days of intended trial vaccination. 8. Has received blood, blood products, and/or plasma derivatives or any parenteral immunoglobulin antibody preparation in the past 3 months. 9. Immunosuppressive therapy within 3 months or systemic (e.g., oral or parenteral) corticosteroid treatment within 60 days prior to investigational trial dose administration. 10. Is participating in any clinical trial with another investigational product 30 days prior to the first trial visit or intending to participate in another clinical trial at any time during the conduct of this trial. 11. Participants who are first-degree relatives of individuals involved in the conduct of the trial. 12. Has any history of progressive or severe neurologic disorder, seizure disorder or neuro-inflammatory disease (e.g. Guillain-Barré syndrome). 13. 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. 14. Has received any other vaccines within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to enrollment in this trial with the exception of routine immunizations as per Military Procedures. 15. 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: 1. 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. 2. Acceptable birth control methods are defined as one 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). * Monogamous relationship with vasectomized partner. Partner must have been vasectomized for at least six months prior to the participants' trial entry. 16. If female of childbearing potential and sexually active, refusal to use an acceptable contraceptive method from Day 1 through 6 months after the last dose of trial vaccine. In addition, they must be advised not to donate ova during this period. 17. Has any positive or indeterminate pregnancy test.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Moderate or Severe Acute Gastroenteritis (AGE) Occurring for >7 Days After Dosing Due to GI.1 or GII.4 Norovirus Strains (Excluding Co-infection) | Up to Day 47 | Acute gastroenteritis (AGE) is a sudden inflammation or swelling in the lining of the stomach causing diarrhea and vomiting. A norovirus AGE case was defined as meeting the work-up definition plus a norovirus positive stool sample or vomitus sample confirmed by reverse transcriptase polymerase chain reaction (RT-PCR). The severity of AGE was graded by the investigator as per CTCAE criteria. AGE occurring due to NoV strains excluding co-infection with Salmonella, Shigella or Campylobacter is reported. The Norovirus strains included: GI.1, GI.7a, GII.2 and GII.4. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Moderate or Severe AGE Occurring >7 Days After Dosing Due to Any Norovirus Strain (Excluding Co-infection) | Up to Day 47 | Acute gastroenteritis (AGE) is a sudden inflammation or swelling in the lining of the stomach causing diarrhea and vomiting. A norovirus AGE case was defined as meeting the work-up definition plus a norovirus positive stool sample or vomitus sample confirmed by RT-PCR. The severity of AGE was graded by the investigator as per CTCAE criteria. AGE occurring due to NoV strains excluding co-infection with Salmonella, Shigella or Campylobacter is reported. The Norovirus strains included: GI.1, GI.7a, GII.2 and GII.4. |
| Number of Participants With Moderate or Severe AGE Occurring >7 Days After Dosing Due to Any Norovirus Strain (Including Co-infection) | Up to Day 47 | Acute gastroenteritis (AGE) is a sudden inflammation or swelling in the lining of the stomach causing diarrhea and vomiting. A norovirus AGE case was defined as meeting the work-up definition plus a norovirus positive stool sample or vomitus sample confirmed by RT-PCR. The severity of AGE was graded by the investigator as per CTCAE criteria. AGE occurring due to NoV strains including co-infection with Salmonella, Shigella or Campylobacter is reported. The Norovirus strains included: GI.1, GI.7a, GII.2 and GII.4. |
| Number of Participants With Moderate or Severe AGE Occurring >7 Days After Dosing Due to GI.1 or GII.4 Norovirus Strains (Including Co-infection) | Up to Day 47 | Acute gastroenteritis (AGE) is a sudden inflammation or swelling in the lining of the stomach causing diarrhea and vomiting. A norovirus AGE case was defined as meeting the work-up definition plus a norovirus positive stool sample or vomitus sample confirmed by RT-PCR. The severity of AGE was graded by the investigator as per CTCAE criteria. AGE occurring due to NoV strains including co-infection with Salmonella, Shigella or Campylobacter is reported. The Norovirus strains included: GI.1, GI.7a, GII.2 and GII.4. |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at a single investigative site in the United States from 14 June 2016 to 16 June 2018.
Pre-assignment details
Healthy volunteers were enrolled in the study and randomized in 1:1 ratio to receive Norovirus GI.1/GII.4 Bivalent VLP Vaccine or Placebo.
Participants by arm
| Arm | Count |
|---|---|
| Placebo NoV placebo-matching 0.5 mL solution for injection, IM, once, on Day 1. | 2,377 |
| NoV GI.1/GII.4 Bivalent VLP Vaccine NoV GI.1/GII.4 bivalent VLP vaccine, 0.5 mL injection, IM, once, on Day 1. | 2,371 |
| Total | 4,748 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 5 |
| Overall Study | Discharged from US Military Active Service | 117 | 91 |
| Overall Study | Lost to Follow-up | 15 | 27 |
| Overall Study | Pregnancy | 0 | 1 |
| Overall Study | Reason not Specified | 22 | 18 |
| Overall Study | Withdrawal by Subject | 132 | 140 |
Baseline characteristics
| Characteristic | Placebo | Total | NoV GI.1/GII.4 Bivalent VLP Vaccine |
|---|---|---|---|
| Age, Continuous | 20.3 years STANDARD_DEVIATION 2.95 | 20.3 years STANDARD_DEVIATION 2.85 | 20.2 years STANDARD_DEVIATION 2.74 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 521 Participants | 1005 Participants | 484 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1856 Participants | 3743 Participants | 1887 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 29 Participants | 56 Participants | 27 Participants |
| Race (NIH/OMB) Asian | 87 Participants | 175 Participants | 88 Participants |
| Race (NIH/OMB) Black or African American | 351 Participants | 706 Participants | 355 Participants |
| Race (NIH/OMB) More than one race | 165 Participants | 311 Participants | 146 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 22 Participants | 49 Participants | 27 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 55 Participants | 116 Participants | 61 Participants |
| Race (NIH/OMB) White | 1668 Participants | 3335 Participants | 1667 Participants |
| Region of Enrollment United States | 2377 Participants | 4748 Participants | 2371 Participants |
| Sex: Female, Male Female | 423 Participants | 860 Participants | 437 Participants |
| Sex: Female, Male Male | 1954 Participants | 3888 Participants | 1934 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 2,357 | 0 / 2,355 |
| other Total, other adverse events | 88 / 2,357 | 98 / 2,355 |
| serious Total, serious adverse events | 35 / 2,357 | 29 / 2,355 |
Outcome results
Primary
Number of Participants With Moderate or Severe Acute Gastroenteritis (AGE) Occurring for >7 Days After Dosing Due to GI.1 or GII.4 Norovirus Strains (Excluding Co-infection)
Acute gastroenteritis (AGE) is a sudden inflammation or swelling in the lining of the stomach causing diarrhea and vomiting. A norovirus AGE case was defined as meeting the work-up definition plus a norovirus positive stool sample or vomitus sample confirmed by reverse transcriptase polymerase chain reaction (RT-PCR). The severity of AGE was graded by the investigator as per CTCAE criteria. AGE occurring due to NoV strains excluding co-infection with Salmonella, Shigella or Campylobacter is reported. The Norovirus strains included: GI.1, GI.7a, GII.2 and GII.4.
Time frame: Up to Day 47
Population: Full Analysis Set included all participants who were randomized and received the trial dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Moderate or Severe Acute Gastroenteritis (AGE) Occurring for >7 Days After Dosing Due to GI.1 or GII.4 Norovirus Strains (Excluding Co-infection) | 5 Participants |
| NoV GI.1/GII.4 Bivalent VLP Vaccine | Number of Participants With Moderate or Severe Acute Gastroenteritis (AGE) Occurring for >7 Days After Dosing Due to GI.1 or GII.4 Norovirus Strains (Excluding Co-infection) | 1 Participants |
99.99% CI: [-13.181, 0.997]
Secondary
Number of Participants With Moderate or Severe AGE Occurring >7 Days After Dosing Due to Any Norovirus Strain (Excluding Co-infection)
Acute gastroenteritis (AGE) is a sudden inflammation or swelling in the lining of the stomach causing diarrhea and vomiting. A norovirus AGE case was defined as meeting the work-up definition plus a norovirus positive stool sample or vomitus sample confirmed by RT-PCR. The severity of AGE was graded by the investigator as per CTCAE criteria. AGE occurring due to NoV strains excluding co-infection with Salmonella, Shigella or Campylobacter is reported. The Norovirus strains included: GI.1, GI.7a, GII.2 and GII.4.
Time frame: Up to Day 47
Population: Full Analysis Set included all participants who were randomized and received the trial dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Moderate or Severe AGE Occurring >7 Days After Dosing Due to Any Norovirus Strain (Excluding Co-infection) | 26 Participants |
| NoV GI.1/GII.4 Bivalent VLP Vaccine | Number of Participants With Moderate or Severe AGE Occurring >7 Days After Dosing Due to Any Norovirus Strain (Excluding Co-infection) | 10 Participants |
95.01% CI: [0.208, 0.816]
Secondary
Number of Participants With Moderate or Severe AGE Occurring >7 Days After Dosing Due to Any Norovirus Strain (Including Co-infection)
Acute gastroenteritis (AGE) is a sudden inflammation or swelling in the lining of the stomach causing diarrhea and vomiting. A norovirus AGE case was defined as meeting the work-up definition plus a norovirus positive stool sample or vomitus sample confirmed by RT-PCR. The severity of AGE was graded by the investigator as per CTCAE criteria. AGE occurring due to NoV strains including co-infection with Salmonella, Shigella or Campylobacter is reported. The Norovirus strains included: GI.1, GI.7a, GII.2 and GII.4.
Time frame: Up to Day 47
Population: Full Analysis Set included all participants who were randomized and received the trial dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Moderate or Severe AGE Occurring >7 Days After Dosing Due to Any Norovirus Strain (Including Co-infection) | 26 Participants |
| NoV GI.1/GII.4 Bivalent VLP Vaccine | Number of Participants With Moderate or Severe AGE Occurring >7 Days After Dosing Due to Any Norovirus Strain (Including Co-infection) | 10 Participants |
95% CI: [0.208, 0.816]
Secondary
Number of Participants With Moderate or Severe AGE Occurring >7 Days After Dosing Due to GI.1 or GII.4 Norovirus Strains (Including Co-infection)
Acute gastroenteritis (AGE) is a sudden inflammation or swelling in the lining of the stomach causing diarrhea and vomiting. A norovirus AGE case was defined as meeting the work-up definition plus a norovirus positive stool sample or vomitus sample confirmed by RT-PCR. The severity of AGE was graded by the investigator as per CTCAE criteria. AGE occurring due to NoV strains including co-infection with Salmonella, Shigella or Campylobacter is reported. The Norovirus strains included: GI.1, GI.7a, GII.2 and GII.4.
Time frame: Up to Day 47
Population: Full Analysis Set included all participants who were randomized and received the trial dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Moderate or Severe AGE Occurring >7 Days After Dosing Due to GI.1 or GII.4 Norovirus Strains (Including Co-infection) | 5 Participants |
| NoV GI.1/GII.4 Bivalent VLP Vaccine | Number of Participants With Moderate or Severe AGE Occurring >7 Days After Dosing Due to GI.1 or GII.4 Norovirus Strains (Including Co-infection) | 1 Participants |
95% CI: [-0.711, 0.977]