Trial Outcomes & Findings for Serologic Assay Validation, Proficiency Testing, Safety and Immunogenicity of Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine (NCT NCT02475278)

NCT ID: NCT02475278

Last Updated: 2018-02-22

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 50 participants
• Primary outcome timeframe: Day 8
• Results posted on: 2018-02-22

Participant Flow

Participants took part in the study at 1 investigative site in the United States from 26 February 2015 to 9 September 2015.

Healthy volunteers were enrolled in 1 treatment group and received a single dose of NoV Vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP, adjuvanted with 500 µg aluminum hydroxide).

Participant milestones

Measure	NoV Vaccine Norovirus GI.1/GII.4 bivalent Virus-Like Particle (VLP) vaccine (NoV Vaccine) (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP, adjuvanted with 500 µg aluminum hydroxide), intramuscular (IM) injection, once on Day 1.
Overall Study STARTED	50
Overall Study COMPLETED	48
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Measure	NoV Vaccine Norovirus GI.1/GII.4 bivalent Virus-Like Particle (VLP) vaccine (NoV Vaccine) (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP, adjuvanted with 500 µg aluminum hydroxide), intramuscular (IM) injection, once on Day 1.
Overall Study Lost to Follow-up	1
Overall Study Reason Not Specified	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	NoV Vaccine n=50 Participants Norovirus GI.1/GII.4 bivalent Virus-Like Particle (VLP) vaccine (NoV Vaccine) (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP, adjuvanted with 500 µg aluminum hydroxide), intramuscular (IM) injection, once on Day 1.
Age, Continuous	30.8 years STANDARD_DEVIATION 9.28 • n=5 Participants
Sex: Female, Male Female	22 Participants n=5 Participants
Sex: Female, Male Male	28 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	18 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	32 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race/Ethnicity, Customized Black Or African American	14 participants n=5 Participants
Race/Ethnicity, Customized White	36 participants n=5 Participants
Region of Enrollment United States	50 participants n=5 Participants
Height	171.42 cm STANDARD_DEVIATION 9.115 • n=5 Participants
Weight	79.08 kg STANDARD_DEVIATION 13.864 • n=5 Participants
Body Mass Index (BMI)	26.88 kg/m^2 STANDARD_DEVIATION 4.025 • n=5 Participants

PRIMARY outcome

Timeframe: Day 8

Population: Safety Analysis Set, all participants who received the trial vaccine (NoV Vaccine).

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

Outcome measures

Measure	NoV Vaccine n=50 Participants Norovirus GI.1/GII.4 bivalent Virus-Like Particle (VLP) vaccine (NoV Vaccine) (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP, adjuvanted with 500 µg aluminum hydroxide), intramuscular (IM) injection, once on Day 1.
Number of Participants With Serum Samples Obtained on Day 8 for Assessment of Seropositivity for Both Anti-NoV GI.1 VLP and GII.4 VLP Antibodies	48 participants

PRIMARY outcome

Timeframe: Day 15

Population: Safety Analysis Set, all participants who received the trial vaccine (NoV Vaccine).

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

Outcome measures

Measure	NoV Vaccine n=50 Participants Norovirus GI.1/GII.4 bivalent Virus-Like Particle (VLP) vaccine (NoV Vaccine) (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP, adjuvanted with 500 µg aluminum hydroxide), intramuscular (IM) injection, once on Day 1.
Number of Participants With Serum Samples Obtained on Day 15 for Assessment of Seropositivity for Both Anti-NoV GI.1 VLP and GII.4 VLP Antibodies	48 participants

PRIMARY outcome

Timeframe: Day 29

Population: Safety Analysis Set, all participants who received the trial vaccine (NoV Vaccine).

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

Outcome measures

Measure	NoV Vaccine n=50 Participants Norovirus GI.1/GII.4 bivalent Virus-Like Particle (VLP) vaccine (NoV Vaccine) (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP, adjuvanted with 500 µg aluminum hydroxide), intramuscular (IM) injection, once on Day 1.
Number of Participants With Serum Samples Obtained on Day 29 for Assessment of Seropositivity for Both Anti-NoV GI.1 VLP and GII.4 VLP Antibodies	46 participants

SECONDARY outcome

Timeframe: Days 1 through 7

Population: Safety Analysis Set, all participants who received the trial vaccine (NoV Vaccine).

Safety assessment included collection of solicited local AEs for 7 days following vaccination (including the day of vaccination) by using diary cards. Solicited local injection site AEs are defined as pain, erythema (redness), induration and swelling. Pain is summarized as either none or any, where 'any' will be broken down into the following severity categories: mild, moderate, severe. Erythema, swelling and induration are recorded as yes or no, where the definition of 'yes' is any area ≥2.5 cm; and 'yes' is further broken down into the following severity categories: ≥2.5 cm - ≤5.0 cm (mild intensity), >5.0 cm - ≤ 10.0 cm (moderate intensity), >10.0 cm severe intensity). Injection site AEs are presented as the percentage of participants experiencing a reaction, by reaction type, overall and by severity, using the participant's worst reported severity grade. Only categories for which there was at least 1 participant are reported.

Outcome measures

Measure	NoV Vaccine n=50 Participants Norovirus GI.1/GII.4 bivalent Virus-Like Particle (VLP) vaccine (NoV Vaccine) (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP, adjuvanted with 500 µg aluminum hydroxide), intramuscular (IM) injection, once on Day 1.
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) by Maximum Severity Pain, Any	54.0 percentage of participants
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) by Maximum Severity Pain, Mild	44.0 percentage of participants
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) by Maximum Severity Pain, Moderate	10.0 percentage of participants

SECONDARY outcome

Timeframe: Days 1 through 7

Population: Safety Analysis Set, all participants who received the trial vaccine (NoV Vaccine).

Safety assessment included collection of solicited systemic AEs for 7 days following vaccination (including the day of vaccination) by using diary cards. Solicited systemic AEs are defined as headache, fatigue, myalgia, arthralgia, vomiting and diarrhea and are summarized as either none or any, where 'any' will be broken down into the following severity categories: mild, moderate, severe. Solicited systemic AEs are presented as the percentage of participants experiencing a solicited systemic AE, by AE, overall and by severity, using the participant's worst reported severity grade. Only categories for which there was at least 1 participant are reported.

Outcome measures

Measure	NoV Vaccine n=50 Participants Norovirus GI.1/GII.4 bivalent Virus-Like Particle (VLP) vaccine (NoV Vaccine) (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP, adjuvanted with 500 µg aluminum hydroxide), intramuscular (IM) injection, once on Day 1.
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Maximum Severity Headache, Any	24.0 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Maximum Severity Headache, Mild	18.0 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Maximum Severity Headache, Moderate	6.0 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Maximum Severity Fatigue, Any	34.0 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Maximum Severity Fatigue, Mild	30.0 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Maximum Severity Fatigue, Moderate	4.0 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Maximum Severity Myalgia, Any	12.0 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Maximum Severity Myalgia, Mild	12.0 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Maximum Severity Arthralgia, Any	6.0 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Maximum Severity Arthralgia, Mild	6.0 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Maximum Severity Vomiting, Any	2.0 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Maximum Severity Vomiting, Mild	2.0 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Maximum Severity Diarrhea, Any	12.0 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Maximum Severity Diarrhea, Mild	10.0 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Maximum Severity Diarrhea, Moderate	2.0 percentage of participants

SECONDARY outcome

Timeframe: Days 1 to 7 days after vaccination

Population: Safety Analysis Set, all participants who received the trial vaccine (NoV Vaccine).

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

Outcome measures

Measure	NoV Vaccine n=50 Participants Norovirus GI.1/GII.4 bivalent Virus-Like Particle (VLP) vaccine (NoV Vaccine) (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP, adjuvanted with 500 µg aluminum hydroxide), intramuscular (IM) injection, once on Day 1.
Percentage of Participants With Elevated Daily Oral Temperature	0.0 percentage of participants

SECONDARY outcome

Timeframe: Days 1 through 28

Population: Safety Analysis Set, all participants who received the trial vaccine (NoV Vaccine).

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

Outcome measures

Measure	NoV Vaccine n=50 Participants Norovirus GI.1/GII.4 bivalent Virus-Like Particle (VLP) vaccine (NoV Vaccine) (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP, adjuvanted with 500 µg aluminum hydroxide), intramuscular (IM) injection, once on Day 1.
Percentage of Participants With Unsolicited Adverse Events (AEs) by Maximum Severity Unsolicited Adverse Events, Any	22.0 percentage of participants
Percentage of Participants With Unsolicited Adverse Events (AEs) by Maximum Severity Unsolicited Adverse Events, Mild	14.0 percentage of participants
Percentage of Participants With Unsolicited Adverse Events (AEs) by Maximum Severity Unsolicited Adverse Events, Moderate	6.0 percentage of participants
Percentage of Participants With Unsolicited Adverse Events (AEs) by Maximum Severity Unsolicited Adverse Events, Severe	2.0 percentage of participants

SECONDARY outcome

Timeframe: Day 1 up to Day 183

Population: Safety Analysis Set, all participants who received the trial vaccine (NoV Vaccine).

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.

Outcome measures

Measure	NoV Vaccine n=50 Participants Norovirus GI.1/GII.4 bivalent Virus-Like Particle (VLP) vaccine (NoV Vaccine) (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP, adjuvanted with 500 µg aluminum hydroxide), intramuscular (IM) injection, once on Day 1.
Percentage of Participants Experiencing Serious Adverse Events	2.0 percentage of participants

Adverse Events

NoV Vaccine

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Measure

NoV Vaccine n=50 participants at risk Norovirus GI.1/GII.4 bivalent Virus-Like Particle (VLP) vaccine (NoV Vaccine) (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP, adjuvanted with 500 µg aluminum hydroxide), intramuscular (IM) injection, once on Day 1.

General disorders Unevaluable event

2.0% 1/50 • Unsolicited AEs 28 days after vaccination (Day 1 to 28) and Serious Adverse Events (SAEs) throughout the trial (Up to Day 183). At each visit the investigator documented any occurrence of AEs. Any event spontaneously reported by participant or observed by investigator was recorded, irrespective of relation to study treatment. Non-serious unsolicited AEs reported below. Non-serious solicited AEs reported in the outcome measure section.

Other adverse events

Measure

NoV Vaccine n=50 participants at risk Norovirus GI.1/GII.4 bivalent Virus-Like Particle (VLP) vaccine (NoV Vaccine) (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP, adjuvanted with 500 µg aluminum hydroxide), intramuscular (IM) injection, once on Day 1.

Infections and infestations Rhinitis

6.0% 3/50 • Unsolicited AEs 28 days after vaccination (Day 1 to 28) and Serious Adverse Events (SAEs) throughout the trial (Up to Day 183). At each visit the investigator documented any occurrence of AEs. Any event spontaneously reported by participant or observed by investigator was recorded, irrespective of relation to study treatment. Non-serious unsolicited AEs reported below. Non-serious solicited AEs reported in the outcome measure section.

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: trialdisclosures@takeda.com

Results disclosure agreements

• Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
• Publication restrictions are in place

Restriction type: OTHER