Safety and Immunogenicity of Norovirus GI.1/GII.4 Bivalent VLP Vaccine

NCT02038907 | Completed Phase 2 Results

• 3 other identifiers: NOR-1072013-001419-64U1111-1147-3239
• Study Type: interventional
• Target: 420
• Locations: 1 country
• Sites: 2

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), Aluminum Hydroxide and MPL adjuvant (3-O-desacyl-4'-monophosphoryl lipid A) for further development.

Conditions

Healthy Volunteers; Norovirus, Prevention

Keywords

Norovirus, vaccination

Outcome Measures

Primary Outcomes (9)

• Percentage of Participants With a Seroresponse (Pan-Ig ELISA)

  Seroresponse was 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).

  Baseline and Day 56

• Percentage of Participants With Solicited Local Adverse Events (AEs) at Injection Site After Dose 1

  Solicited local AEs at injection site are defined as: pain, erythema, induration, and swelling that occurred within 7 days after each vaccination.

  Days 1 through 7

• Percentage of Participants With Solicited Local Adverse Events (AEs) at Injection Site After Dose 2

  Solicited local AEs at injection site are defined as: pain, erythema, induration, and swelling that occurred within 7 days after each vaccination.

  Days 28 through 34

• Percentage of Participants With Solicited Systemic Adverse Events (AEs) After Dose 1

  Solicited systemic AEs are defined as: headache, fatigue, myalgia, arthralgia, vomiting, and diarrhea that occurred within 7 days after each vaccination.

  Days 1 through 7

• Percentage of Participants With Solicited Systemic Adverse Events (AEs) After Dose 2

  Solicited systemic AEs are defined as: headache, fatigue, myalgia, arthralgia, vomiting, and diarrhea that occurred within 7 days after each vaccination.

  Days 28 through 34

• Oral Body Temperature Within 7 Days After Dose 1

  Oral body temperature measurement is to be performed using the thermometer provided by the site for 7 days after each vaccination. The highest body temperature observed each day will be recorded on the Diary Card also provided by the site.

  Days 1 through 7

• Oral Body Temperature Within 7 Days After Dose 2

  Oral body temperature measurement is to be performed using the thermometer provided by the site for 7 days after each vaccination. The highest body temperature observed each day will be recorded on the Diary Card also provided by the site.

  Days 28 through 34

• Percentage of Participants With Unsolicited Adverse Events (AEs)

  Unsolicited AEs are any AEs that are not solicited local or systemic AEs, as defined by this study.

  Day 1 up to Day 56

• Percentage of Participants With Serious Adverse Events (SAEs)

  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.

  Day 1 up to Day 393

Secondary Outcomes (31)

• Percentage of Participants With a Seroresponse on Day 28, Day 208 and Day 393 (Pan-Ig ELISA)

  Baseline and Days 28, 208 and 393

• Percentage of Participants With a 4-Fold Rise or Greater in GI.1 VLP Antibody Titer (Pan-Ig ELISA)

  Baseline and Days 28, 56, 208 and 393

• Percentage of Participants With a 4-Fold Rise or Greater in GII.4 VLP Antibody Titer (Pan-Ig ELISA)

  Baseline and Days 28, 56, 208 and 393

• Geometric Mean Titer (GMT) of GI.1 VLP Antibody Titers (Pan-Ig ELISA)

  Day 1 (Baseline) and Days 28, 56, 208 and 393

• Geometric Mean Titer (GMT) of GII.4 VLP Antibody Titers (Pan-Ig ELISA)

  Day 1 (Baseline) and Days 28, 56, 208 and 393

Study Arms (14)

GI.1/GII.4 (15/15) - MPL (50)

EXPERIMENTAL

Hepatitis A vaccine, intramuscular (IM), on Day 1, followed by norovirus bivalent virus like particle (VLP) vaccine (15 µg of GI.1 norovirus virus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 50 µg monophosphoryl lipid A (MLP) and 500 µg aluminum hydroxide, IM on Day 28.

Biological: Hepatitis A Vaccine; Biological: Norovirus Bivalent VLP Vaccine

GI.1/GII.4 (15/50) - MPL (50)

EXPERIMENTAL

Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MLP and 500 µg aluminum hydroxide, IM, on Day 28.

Biological: Hepatitis A Vaccine; Biological: Norovirus Bivalent VLP Vaccine

GI.1/GII.4 (50/50) - MPL (50)

EXPERIMENTAL

Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (50 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MLP and 500 µg aluminum hydroxide, IM, on Day 28.

Biological: Hepatitis A Vaccine; Biological: Norovirus Bivalent VLP Vaccine

GI.1/GII.4 (15/15) - MPL (15)

EXPERIMENTAL

Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 15 µg MLP and 500 µg aluminum hydroxide, IM, on Day 28.

Biological: Hepatitis A Vaccine; Biological: Norovirus Bivalent VLP Vaccine

GI.1/GII.4 (15/50) - MPL (15)

EXPERIMENTAL

IM hepatitis A vaccine on Day 1, followed by IM norovirus bivalent vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 15 µg MLP and 500 µg aluminum hydroxide, on Day 28.

Biological: Hepatitis A Vaccine; Biological: Norovirus Bivalent VLP Vaccine

GI.1/GII.4 (50/50) - MPL (15)

EXPERIMENTAL

Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (50 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 15 µg MLP and 500 µg aluminum hydroxide, IM, on Day 28.

Biological: Hepatitis A Vaccine; Biological: Norovirus Bivalent VLP Vaccine

GI.1/GII.4 (15/15)

EXPERIMENTAL

Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, IM, on Day 28.

Biological: Hepatitis A Vaccine; Biological: Norovirus Bivalent VLP Vaccine

GI.1/GII.4 (15/50)

EXPERIMENTAL

Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, IM, on Day 28.

Biological: Hepatitis A Vaccine; Biological: Norovirus Bivalent VLP Vaccine

GI.1/GII.4 (50/50)

EXPERIMENTAL

Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (50 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, IM, on Day 28.

Biological: Hepatitis A Vaccine; Biological: Norovirus Bivalent VLP Vaccine

GI.1/GII.4 (50/150)

EXPERIMENTAL

Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (50 µg of GI.1 norovirus VLP and 150 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, IM, on Day 28.

Biological: Hepatitis A Vaccine; Biological: Norovirus Bivalent VLP Vaccine

GI.1/GII.4 (15/50) - Al(OH)3 (167)

EXPERIMENTAL

Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 167 µg aluminum hydroxide, IM, on Day 28.

Biological: Hepatitis A Vaccine; Biological: Norovirus Bivalent VLP Vaccine

GI.1/GII.4 (15/50) x2

EXPERIMENTAL

Norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, IM, on Day 1 and Day 28.

Biological: Norovirus Bivalent VLP Vaccine

GI.1/GII.4 (50/150) x2

EXPERIMENTAL

Norovirus bivalent VLP vaccine (50 µg of GI.1 norovirus VLP and 150 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, IM, on Day 1 and Day 28.

Biological: Norovirus Bivalent VLP Vaccine

GI.1/GII.4 (15/50) - Al(OH)3 (167) x2

EXPERIMENTAL

Norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 167 µg aluminum hydroxide, IM, on Day 1 and Day 28.

Biological: Norovirus Bivalent VLP Vaccine

Interventions

Hepatitis A Vaccine BIOLOGICAL

Hepatitis A Vaccine IM injection

Also known as: Havrix

GI.1/GII.4 (15/15); GI.1/GII.4 (15/15) - MPL (15); GI.1/GII.4 (15/15) - MPL (50); GI.1/GII.4 (15/50); GI.1/GII.4 (15/50) - Al(OH)3 (167); GI.1/GII.4 (15/50) - MPL (15); GI.1/GII.4 (15/50) - MPL (50); GI.1/GII.4 (50/150); GI.1/GII.4 (50/50); GI.1/GII.4 (50/50) - MPL (15); GI.1/GII.4 (50/50) - MPL (50)

Norovirus Bivalent VLP Vaccine BIOLOGICAL

Norovirus GI.1/GII.4 bivalent VLP vaccine IM injection

GI.1/GII.4 (15/15); GI.1/GII.4 (15/15) - MPL (15); GI.1/GII.4 (15/15) - MPL (50); GI.1/GII.4 (15/50); GI.1/GII.4 (15/50) - Al(OH)3 (167); GI.1/GII.4 (15/50) - Al(OH)3 (167) x2; GI.1/GII.4 (15/50) - MPL (15); GI.1/GII.4 (15/50) - MPL (50); GI.1/GII.4 (15/50) x2; GI.1/GII.4 (50/150); GI.1/GII.4 (50/150) x2; GI.1/GII.4 (50/50); GI.1/GII.4 (50/50) - MPL (15); GI.1/GII.4 (50/50) - MPL (50)

Eligibility Criteria

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

You may qualify if:

• Male and female participants between 18 and 64 years of age at the time of enrollment.
• 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.
• The participant or, when applicable, the participant's legally acceptable representative 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.
• Can comply with trial procedures and are available for the duration of the trial.

You may not qualify if:

• Has received any vaccines containing Hepatitis A vaccine within the past 5 years.
• Has contraindications, warnings, and/or precautions to vaccination with Havrix as specified within the Summary of Product Characteristics.
• 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.
• Known hypersensitivity or allergy to investigational vaccine (including excipients of the investigational vaccine).
• 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 Guillain-Barré syndrome.
• Has history of 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.
• Known or inspected 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.

Sponsors & Collaborators

• Takeda: lead

Study Sites (2)

Universiteit Antwerpen

Edegem, 2650, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

Related Publications (1)

• Leroux-Roels G, Cramer JP, Mendelman PM, Sherwood J, Clemens R, Aerssens A, De Coster I, Borkowski A, Baehner F, Van Damme P. Safety and Immunogenicity of Different Formulations of Norovirus Vaccine Candidate in Healthy Adults: A Randomized, Controlled, Double-Blind Clinical Trial. J Infect Dis. 2018 Jan 30;217(4):597-607. doi: 10.1093/infdis/jix572.

  PMID: 29140444 DERIVED

MeSH Terms

Interventions

Hepatitis A Vaccines

Intervention Hierarchy (Ancestors)

Viral Hepatitis Vaccines; Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Medical Director, Clinical Science
• 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: FACTORIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2014
• First Posted: January 17, 2014
• Study Start: March 28, 2014
• Primary Completion: June 19, 2015
• Study Completion: June 19, 2015
• Last Updated: August 8, 2017
• Results First Posted: August 1, 2016

Record last verified: 2017-08

Locations

BE (2)