Clinical trial NCT02153112: Safety and Immunogenicity of Norovirus GI.1/GII.4 Bivalent Virus-Like Particle (VLP) Vaccine in Children
Official title: A Phase II, Randomized, Double-Blind, Dosage, Safety and Immunogenicity Trial of Intramuscular Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine Combined With Aluminum Hydroxide Adjuvant in Children, Toddlers, and Infants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Norovirus
Keywords: Drug therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2014-06-02
Enrollment: 840
Sex: ALL
Minimum age (years): 6
Maximum age (years): 8
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to select the optimal formulation of the norovirus vaccine from different concentrations of virus-like particles (VLP) combined with aluminum hydroxide for further development in children.

Detailed description: The vaccine being tested in this study is called norovirus GI.1/GII.4 bivalent virus-like particle (VLP) vaccine with aluminum hydroxide. The norovirus vaccine is being tested to assess different formulations of the vaccine that will then be further developed. This study will look at the number of antibodies to norovirus formed in children, toddlers and infants who are administered different formulations of the norovirus vaccine.

The study enrolled 840 patients. Participants will be randomly assigned (by chance) to one of ten treatment groups-which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need).

All participants in Cohort 1 will be vaccinated on Day 1 and Day 29 of the study, and all participants in Cohort 2 will be vaccinated on Day 1, Day 56, and Day 112. All treatment groups in Cohort 1 will receive either one dose of the norovirus vaccine, or two doses. One treatment group in Cohort 2 will receive 2 doses of the norovirus vaccine, and the other group will receive 3. In order to keep the treatment undisclosed to the participant and the doctor in Cohort 1, those randomized to the one-dose groups will receive the norovirus vaccine on Day 1, followed by a dose of placebo vaccine on Day 29. In order to keep the treatment arms undisclosed to the participant and the doctor in Cohort 2, those randomized to the two-dose groups will receive the norovirus vaccine on Day 1 and Day 56, followed by a dose of placebo vaccine on Day 112. Placebo vaccine is saline solution. 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 Finland, Panama, and Colombia. The overall time to participate in this study is up to 210 days for participants in Cohort 1 and up to 293 Days for participants in Cohort 2. Participants in Cohort 1 will make 6 visits to the clinic, and participants in Cohort 2 will make 10 visits to the clinic.

Eligibility criteria: Inclusion Criteria:

1. Male and female participants aged between 6 weeks and less than 9 years at the time of enrollment.
2. Are in good health at the time of entry into the trial as determined by medical history, physical examination (including vital signs) and clinical judgment of the investigator.
3. Participants legally authorized representative (LAR) signs and dates a written, informed consent form (ICF) 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. An assent will also be obtained according to age-appropriate country-specific regulations.
4. Participants who can comply with trial procedures and are available for the duration of the trial.

Exclusion Criteria:

1. Participants with a clinically significant active infection (as assessed by the investigator) or body temperature 38.0°C (100.4°F) or higher within 3 days of the intended date of vaccination.
2. Have received antipyretic/analgesic medications within 24 hours prior to the intended vaccine administration.
3. Known hypersensitivity or allergy to investigational vaccine (including excipients of the investigational vaccines).
4. Participants with behavioral or cognitive impairment or psychiatric disease that, in the opinion of the investigator, may interfere with the ability to participate in the trial.
5. Has a history of any progressive or severe neurologic disorder, seizure disorder, or neuroinflammatory disease (eg, Guillain-Barré syndrome).
6. Known or suspected impairment/alteration of immune function, including the following:

   1. Children \<18 months of age with history of repeated episodes of acute otitis media (AOM) in the first 6 months of life (AOM defined as a bulging tympanic membrane) and not to be confused with otitis media with effusion (OME).
   2. 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).
   3. 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.
   4. Receipt of immunostimulants within 60 days prior to Day 1.
   5. 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.
   6. Receipt of immunosuppressive therapy within 6 months prior to Day 1.
   7. Human immunodeficiency virus (HIV) infection or HIV-related disease.
   8. Chronic Hepatitis B or C infection.
   9. Heritable immunodeficiency.
7. Abnormalities of splenic or thymic function.
8. Has a known bleeding diathesis or any condition that may be associated with a prolonged bleeding time.
9. Has any serious chronic or progressive disease according to judgment of the investigator (e.g., neoplasm, insulin dependent diabetes, cardiac, renal, or hepatic disease).
10. 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.
11. Has received any other vaccines within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to enrollment in this trial.
12. Are first degree relatives of individuals involved in trial conduct.
13. Has a history of autoimmune disease.

Primary outcomes:
measure: Percentage of Participants With a Seroresponse (Pan-Ig ELISA) in Cohort 1
timeFrame: Day 57
measure: Percentage of Participants With a Seroresponse (Pan-Ig ELISA) in Cohort 2
timeFrame: Day 140
measure: Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 1
timeFrame: Day 1 after either of the vaccination given on Days 1, 29, 56 or 112
measure: Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 2
timeFrame: Day 1 after either of the vaccination given on Days 1, 29, 56 or 112
measure: Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 3
timeFrame: Day 3 after either of the vaccination given on Days 1, 29, 56 or 112
measure: Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 4
timeFrame: Day 4 after either of the vaccination given on Days 1, 29, 56 or 112
measure: Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 5
timeFrame: Day 5 after either of the vaccination given on Days 1, 29, 56 or 112
measure: Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 6
timeFrame: Day 6 after either of the vaccination given on Days 1, 29, 56 or 112
measure: Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 7
timeFrame: Day 7 after either of the vaccination given on Days 1, 29, 56 or 112
measure: Percentage of Participants With Solicited Systemic Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination
timeFrame: Days 1 through 7 after each vaccination given on Days 1, 29, 56 or 112
measure: Body Temperature Through Day 7 Following Either Vaccination
timeFrame: Post-vaccination approximately 30 minutes and 6 hours later, then daily through Day 7 after each vaccination given on Days 1, 29, 56 or 112
measure: Percentage of Participants With at Least One Unsolicited AE Following Either Vaccination Dose
timeFrame: Unsolicited AEs were collected within 28 days of all vaccinations (Day 1 to 57 for Cohort 1 and Day 1 to 140 for Cohort 2)
measure: Percentage of Participants With Serious Adverse Events (SAEs)
timeFrame: Cohort 1: Day 1 up to Day 210; Cohort 2: Day 1 up to Day 293
Secondary outcomes:
measure: Percentage of Participants With a Seroresponse for GI.1 Virus-Like Particle (VLP) (Pan-Ig ELISA)
timeFrame: Cohort 1: Day 57; Cohort 2: Day 140
measure: Percentage of Participants With a Seroresponse for GII.4 Virus-Like Particle (VLP) (Pan-Ig ELISA)
timeFrame: Cohort 1: Day 57; Cohort 2: Day 140
measure: Geometric Mean Titer (GMT) of GI.1 VLP Antibody Titers (Pan-Ig ELISA)
timeFrame: Cohort 1: Day 57; Cohort 2: Day 140
measure: Geometric Mean Titer (GMT) of GII.4 VLP Antibody Titers (Pan-Ig ELISA)
timeFrame: Cohort 1: Day 57; Cohort 2: Day 140
measure: Geometric Mean Fold Rise (GMFR) of GI.1 VLP Antibody Titers (Pan-Ig ELISA)
timeFrame: Cohort 1: Day 57; Cohort 2: Day 140
measure: Geometric Mean Fold Rise (GMFR) of GII.4 VLP Antibody Titers (Pan-Ig ELISA)
timeFrame: Cohort 1: Day 57; Cohort 2: Day 140
measure: Percentage of Participants With a 4-Fold Rise or Greater in Serum Antibody Titers for GI.1 VLP and GII.4 VLP (HBGA)
timeFrame: Cohort 1: Day 57; Cohort 2: Day 140
measure: Percentage of Participants With a 4-Fold Rise or Greater in Serum GI.1 VLP Antibody Titers (HBGA)
timeFrame: Cohort 1: Day 57; Cohort 2: Day 140
measure: Percentage of Participants With a 4-Fold Rise or Greater in Serum GII.4 VLP Antibody Titers (HBGA)
timeFrame: Cohort 1: Day 57; Cohort 2: Day 140
measure: Blocking Titers 50 (BT50) of Anti-Norovirus GI.1 VLP Antibody Titers (HBGA)
timeFrame: Cohort 1: Day 57; Cohort 2: Day 140
measure: Blocking Titers 50 (BT50) of Anti-Norovirus GII.4 VLP Antibody Titers (HBGA)
timeFrame: Cohort 1: Day 57; Cohort 2: Day 140
measure: Geometric Mean Fold Rise (GMFR) of GI.1 VLP Antibody Titers (HBGA)
timeFrame: Cohort 1: Day 57; Cohort 2: Day 140
measure: Geometric Mean Fold Rise (GMFR) of GII.4 VLP Antibody Titers (HBGA)
timeFrame: Cohort 1: Day 57; Cohort 2: Day 140
measure: Percentage of Participants With Any Adverse Event (AE) Leading to Withdrawal From the Study
timeFrame: Cohort 1: Day 1 up to Day 210; Cohort 2: Day 1 up to Day 293
Other outcomes:
Locations:
city: Cali
country: Colombia
facility: Centro de Estudios em Infectologia Pediatrica SAS
state: San Fernando
city: Espoo
country: Finland
facility: Espoon Rokotetutkimusklinikka
city: Helsinki
country: Finland
facility: Etela-Helsingin Rokotetutkimusklinikka
city: Helsinki
country: Finland
facility: Ita-Helsingin Rokotetutkimusklinikka
city: Jarvenpaan
country: Finland
facility: Jarvenpaan Rokotetutkimusklinikka
city: Oulu
country: Finland
facility: Oulun Rokotetutkimusklinikka
city: Pori
country: Finland
facility: Porin Rokotetutkimusklinikka
city: Seinajoki
country: Finland
facility: Seinajoen Rokotetutkimusklinikka
city: Tampere
country: Finland
facility: Tampere Vaccine Research Clinic
city: Turku
country: Finland
facility: Turun Rokotetutkimusklinikka
city: Ciudad de Panama
country: Panama
facility: CEVAXIN Plaza Carolina - Ciudad de Panama
city: Panama
country: Panama
facility: CEVAXIN
Study officials:
affiliation: Takeda
name: Medical Director Clinical Science
role: STUDY_DIRECTOR
References: