Safety and Immunogenicity of Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine in an Elderly Population

NCT02661490 | Completed Phase 2 Results DMC

• 2 other identifiers: NOR-204U1111-1162-4913
• Study Type: interventional
• Target: 320
• Locations: 1 country
• Sites: 10

Brief Summary

The purpose of this study is to further develop a formulation and dose regimen of the norovirus GI.1/GII.4 bivalent virus-like particle (VLP) vaccine that is immunogenic and safe in an elderly population aged 60 years and above.

Conditions

Norovirus

Keywords

Norovirus

Outcome Measures

Primary Outcomes (10)

• Percentage of Participants With a 4-Fold Rise or Greater in Serum Anti-norovirus Antibody Titers for Both GI.1 and GII.4 Virus Like Particles (VLP) as Measured by Histoblood Group Antigen (HBGA) Blocking Assay on Day 57

  Day 57

• Percentage of Participants With Solicited Local Adverse Events (AEs) at Injection Site for 7-day Period (Including Day of Vaccination) After First Vaccination on Day 1

  Solicited local AEs at the injection site that occurred within 7 days after each vaccination were collected using a diary and included pain, erythema swelling and induration.

  Within 7 days of first vaccination on Day 1

• Percentage of Participants With Solicited Local Adverse Events (AEs) at Injection Site for 7-day Period (Including Day of Vaccination) After Second Vaccination on Day 29

  Solicited local AEs at the injection site that occurred within 7 days after each vaccination were collected using a diary and included pain, erythema, swelling and induration.

  Within 7 days of second vaccination on Day 29

• Percentage of Participants With Solicited Systemic Adverse Events (AEs) for 7-day Period (Including Day of Vaccination) After First Vaccination on Day 1

  Solicited systemic AEs that occurred within 7 days after each vaccination were collected using a diary and included headache, fatigue, myalgia, arthralgia, vomiting, and diarrhea.

  Within 7 days of first vaccination on Day 1

• Percentage of Participants With Solicited Systemic Adverse Events (AEs) for 7-day Period (Including Day of Vaccination) After Second Vaccination on Day 29

  Solicited systemic AEs that occurred within 7 days after each vaccination were collected using a diary and included headache, fatigue, myalgia, arthralgia, vomiting, and diarrhea.

  Within 7 days of second vaccination on Day 29

• Percentage of Participants With Elevated Body Temperature ≥38°C (Defined as Fever) for 7-day Period (Including Day of Vaccination) After First Vaccination on Day 1

  The body temperature measurement was performed using the thermometer for 7 days after each vaccination. The highest body temperature observed each day was recorded on the diary card. An elevated temperature is ≥ 38 °C or 100.4°F (considered as fever).

  Within 7 days of first vaccination on Day 1

• Percentage of Participants With Elevated Body Temperature ≥38°C (Defined as Fever) for 7-day Period (Including Day of Vaccination) After Second Vaccination on Day 29

  The body temperature measurement was performed using the thermometer for 7 days after each vaccination. The highest body temperature observed each day was recorded on the diary card. An elevated temperature is ≥ 38 °C or 100.4°F (considered as fever).

  Within 7 days of second vaccination on Day 29

• Percentage of Participants With At Least One Unsolicited Adverse Event (AE) Within 28-days After First Vaccination on Day 1

  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.

  Within 28 days of first vaccination on Day 1

• Percentage of Participants With At Least One Unsolicited Adverse Event (AE) Within 28-days After Second Vaccination on Day 29

  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.

  Within 28 days of second vaccination on Day 29

• Percentage of Participants With At Least One Serious Adverse Event (SAE)

  An SAE is any untoward medical occurrence 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.

  From first vaccination up to Day 393

Secondary Outcomes (16)

• Percentage of Participants With a 4-Fold Rise or Greater in Serum Anti-norovirus Antibody Titers for Both GI.1 VLP and GII.4 VLP as Measured by HBGA Blocking Assay

  Days 8, 29, 36, 211 and 393

• Percentage of Participants With a 4-Fold Rise or Greater in Serum Anti-norovirus GI.1 VLP Antibody Titers (HBGA)

  Days 8, 29, 36, 57, 211 and 393

• Percentage of Participants With a 4-Fold Rise or Greater in Serum Anti-norovirus GII.4 VLP Antibody Titers (HBGA)

  Days 8, 29, 36, 57, 211 and 393

• Geometric Mean Titer (GMT) GI.1 VLP Antibody Titers (HBGA)

  Baseline (Day 1), Days 8, 29, 36, 57, 211 and 393

• GMT of Anti-norovirus GII.4 VLP Antibody Titers (HBGA)

  Baseline (Day 1), Days 8, 29, 36, 57, 211 and 393

Study Arms (5)

Arm 1: NoV Vaccine Formulation A _1-Dose

EXPERIMENTAL

Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, intramuscularly (IM), on Day 1, followed by norovirus (NoV) GI.1 (15 μg)/GII.4 (50 μg) bivalent virus-like particle (VLP) vaccine (Formulation A), IM, on Day 29.

Biological: Norovirus GI.1/GII.4 Bivalent VLP Vaccine; Drug: 0.9% sodium chloride (saline)

Arm 2: NoV Vaccine Formulation A _2-Dose

EXPERIMENTAL

Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Days 1 and 29.

Biological: Norovirus GI.1/GII.4 Bivalent VLP Vaccine

Arm 3: NoV Vaccine Formulation B_1-Dose

EXPERIMENTAL

Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg monophosphoryl lipid A (MPL) (Formulation B), IM, on Day 29.

Drug: 0.9% sodium chloride (saline); Biological: Norovirus GI.1/GII.4 Bivalent VLP Vaccine

Arm 4: NoV Vaccine Formulation B_2-Dose

EXPERIMENTAL

Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg MPL (Formulation B), IM, on Days 1 and 29.

Biological: Norovirus GI.1/GII.4 Bivalent VLP Vaccine

Arm 5: NoV Vaccine Formulation A_1-Dose

EXPERIMENTAL

Participants 18 to 49 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM, on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Day 29.

Biological: Norovirus GI.1/GII.4 Bivalent VLP Vaccine; Drug: 0.9% sodium chloride (saline)

Interventions

Norovirus GI.1/GII.4 Bivalent VLP Vaccine BIOLOGICAL

Norovirus GI.1/GII.4 bivalent VLP vaccine adjuvanted with aluminum hydroxide, without MPL for IM injection

Arm 1: NoV Vaccine Formulation A _1-Dose; Arm 2: NoV Vaccine Formulation A _2-Dose; Arm 5: NoV Vaccine Formulation A_1-Dose

0.9% sodium chloride (saline) DRUG

norovirus bivalent placebo-matching vaccine

Arm 1: NoV Vaccine Formulation A _1-Dose; Arm 3: NoV Vaccine Formulation B_1-Dose; Arm 5: NoV Vaccine Formulation A_1-Dose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Is aged 18 to 49 years, or 60 years and older at the time of enrollment;
• Participant 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;
• Participants who can comply with trial procedures and are available for the duration of follow-up.

You may not qualify if:

• Has a known hypersensitivity or allergy to any of the Norovirus (NoV) GI.1/GII.4 Bivalent virus-like particle (VLP) Vaccine components;
• Has a clinically significant active infection (as assessed by the Investigator) or body temperature ≥38°C/100.4°F within 3 days of the intended date of vaccination;
• Participants with the presence of significant acute or chronic, uncontrolled medical or neuropsychiatric illness. Uncontrolled was defined as:
• Requiring institution of new medical or surgical treatment within 3 months prior to immunization, or Requiring a change in medication dosage in the 3 months prior to immunization due to uncontrolled symptoms or drug toxicity (elective dosage adjustments in stable participants were acceptable), or Hospitalization or an event fulfilling the definition of a serious adverse event within 3 months prior immunization.
• Has any unstable medical or neuropsychiatric condition, which in the Investigator's opinion poses a risk of unusual magnitude for the participant's age group of hospitalization, death, or an event meeting the definition of a serious adverse event within 2 months of immunization. The intent of this criterion is to recognize and allow for the frequent existence of significant health concerns in this population; but exclude those participants who are experiencing an acute decline in health status;
• Has any medical or neuropsychiatric condition, which in the Investigator's opinion, rendered the participant incompetent to provide informed consent or unable to provide valid safety observations and reports;
• 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;
• Participants with any history of progressive or severe neurologic disorder, history of seizure, or history of neuro-inflammatory disease (e.g. Guillain-Barre syndrome);
• Participants with 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 autoimmune disease;
• Has known or suspected impairment/alteration of immune function, including:
• Chronic use of oral steroids (Equivalent to 20 mg/day prednisone ≥ 12 weeks/≥ 2 mg/kg body weight/day prednisone ≥ 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 prednisone ≥ 2 weeks) within 60 days prior to Day 1.
• Receipt of immunosuppressive therapy within 3 months 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.
• Human Immunodeficiency Virus (HIV) infection or HIV-related disease. Genetic immunodeficiency.

Sponsors & Collaborators

• Takeda: lead

Study Sites (10)

Simon Williamson Clinic

Birmingham, Alabama, 35211, United States

Location

Fountain Hills Family Practice, P.C.

Fountain Hills, Arizona, 85268, United States

Location

Southwest Family Medicine

Littleton, Colorado, 80127, United States

Location

Miami Research Associates

Miami, Florida, 33143, United States

Location

Johnson County Clin-Trials

Lenexa, Kansas, 66219, United States

Location

St. Louis University, School of Medicine

St Louis, Missouri, 63104, United States

Location

Regional Clinical Research Inc.

Endwell, New York, 13760, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Cincinnati Childrens Hospital Medical Center

Cincinnati, Ohio, 45229-3039, United States

Location

Group Health Research Institute

Seattle, Washington, 98101, United States

Location

MeSH Terms

Interventions

Sodium Chloride

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director Clinical Science

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2016
• First Posted: January 22, 2016
• Study Start: February 1, 2016
• Primary Completion: October 28, 2016
• Study Completion: September 29, 2017
• Last Updated: May 18, 2020
• Results First Posted: May 18, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will share

Locations

US (10)