Safety and Immunogenicity of Norovirus Bivalent Virus-Like Particle Vaccine in Healthy Adults

NCT02142504 | Completed Phase 2 Results DMC

• 2 other identifiers: NOR-201U1111-1155-8803
• Study Type: interventional
• Target: 454
• Locations: 1 country
• Sites: 10

Brief Summary

The purpose of this study is to evaluate the safety of the norovirus bivalent virus-like particle (VLP) vaccine for further development by assessing the rates of serious adverse events (SAEs), unsolicited adverse events (AEs), solicited local and solicited systemic AEs, Adverse Events of Special Interest (AESIs) and AEs leading to participant's withdrawal from the trial.

Conditions

Norovirus Prevention

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (9)

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

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

  Days 1 through 7

• Percentage of Participants With Solicited Systemic Adverse Events (AEs) After the First Injection

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

  Days 1 through 7

• Percentage of Participants With Elevated Daily Oral Temperature (Fever) After the First Injection

  Fever is defined as greater than or equal to 38°C (100.4°F). Oral body temperature measurement was performed using the thermometer provided by the site for 7 days after each injection. The highest body temperature observed each day was recorded on the Diary Card also provided by the site.

  Days 1 through 7

• Percentage of Participants With Unsolicited Adverse Events (AEs) After the First Injection

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

  Days 1 through 28

• Percentage of Participants With Serious Adverse Events (SAEs) After the First Injection

  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.

  From first injection (Day 1) to second injection pre-dose (Up to Day 365)

• Percentage of Participants With Serious Adverse Events (SAEs) After the Second Injection

  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.

  From second injection (Day 365) to 6 months after second injection (Up to Day 545)

• Percentage of Participants With Adverse Events of Special Interest (AESI) After the First Injection

  AESIs are AEs that are not solicited local or systemic AEs, they are predefined AEs that required close monitoring and prompt reporting to the sponsor. AESI included protocol specified Cardiac Disorders, Gastrointestinal Disorders, Immune System Disorders, Infections and Infestations, Musculoskeletal and Connective Tissue Diseases, Neuroinflammatory Disorders, Renal and Urinary Disorders, Skin Disorders, Thyroid Disorders, Vascular Disorders and Other Disorders.

  From first injection (Day 1) to second injection pre-dose (Up to Day 365)

• Percentage of Participants With Adverse Events of Special Interest (AESI) After the Second Injection

  AESIs are AEs that are not solicited local or systemic AEs, they are predefined AEs that required close monitoring and prompt reporting to the sponsor. AESI included protocol specified Cardiac Disorders, Gastrointestinal Disorders, Immune System Disorders, Infections and Infestations, Musculoskeletal and Connective Tissue Diseases, Neuroinflammatory Disorders, Renal and Urinary Disorders, Skin Disorders, Thyroid Disorders, Vascular Disorders and Other Disorders.

  From second injection (Day 365) to 6 months after second injection (Up to Day 545)

• Percentage of Participants With Any Adverse Event (AE) Leading to Withdrawal From the Study

  Withdrawal due to an AE occurred if the participant experienced an AE that required early termination because continued participation imposed an unacceptable risk to the participant's health or the participant was unwilling to continue because of the AE.

  Unsolicited AEs 28 days after each injection (Days 1 to 28 and Days 365 to 393), and Serious Adverse Events (SAEs) throughout the trial (Up to Day 545)

Secondary Outcomes (18)

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

  Days 365 through 371

• Percentage of Participants With Solicited Systemic Adverse Events (AEs) After the Second Injection

  Days 365 through 371

• Percentage of Participants With Elevated Daily Oral Temperature (Fever) After the Second Injection

  Days 365 through 371

• Percentage of Participants With Unsolicited Adverse Events (AEs) After the Second Injection

  Days 365 through 393

• Percentage of Participants With a Seroresponse in Both Serum Anti-norovirus GI.1 VLP and GII.4 VLP (Pan-Ig ELISA)

  Baseline and Day 28

Study Arms (3)

GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)

EXPERIMENTAL

Intramuscular (IM) norovirus bivalent virus like particle (VLP) vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg monophosphoryl lipid A (MPL) and 500 µg aluminum hydroxide, on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide (no MPL), on Day 365.

Biological: Norovirus Bivalent VLP Vaccine

GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)

EXPERIMENTAL

IM norovirus bivalent VLP vaccine (50 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg monophosphoryl lipid A (MPL) and 500 µg aluminum hydroxide, on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide (no MPL), on Day 365.

Biological: Norovirus Bivalent VLP Vaccine

Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)

PLACEBO COMPARATOR

IM saline placebo on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP ) adjuvanted with 500 µg aluminum hydroxide (no MPL), on Day 365.

Biological: Norovirus Bivalent VLP Vaccine; Drug: Placebo (Saline)

Interventions

Norovirus Bivalent VLP Vaccine BIOLOGICAL

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

GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL); GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL); Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)

Placebo (Saline) DRUG

Placebo-matching norovirus bivalent VLP vaccine

Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male and female participants aged 18 to 49 years of age at the time of enrollment.
• Are in good health at the time of entry into the trial as determined by medical history, physical examination and clinical judgment of the investigator.
• Participants with a signed informed consent form and any required privacy authorization prior to the initiation of any trial procedures and 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 a history of acute gastroenteritis within 14 days of enrollment.
• 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.
• Has known hypersensitivity or allergy to any of the bivalent norovirus virus-like particle (VLP) vaccine components (including excipients of the investigational vaccines).
• 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 neuro-inflammatory disease (e.g., Guillain-Barré syndrome).
• 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.
• Has known or suspected 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.
• Heritable immunodeficiency.

Sponsors & Collaborators

• Takeda: lead

Study Sites (10)

California Research Foundation

San Diego, California, 92103-6204, United States

Location

Benchmark Research San Francisco

San Francisco, California, 94108, United States

Location

Clin Research of South Florida

Coral Gables, Florida, 33134, United States

Location

SNBL

Baltimore, Maryland, 21201, United States

Location

St. Louis University, School of Medicine

St Louis, Missouri, 63104, United States

Location

Rochester Clinical Research

Rochester, New York, 14609, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Cincinnati Childrens Hospital Medical Center

Cincinnati, Ohio, 45206, United States

Location

Benchmark Research Austin

Austin, Texas, 78705, United States

Location

Baylor College of Medicine

Houston, Texas, 77030-3498, United States

Location

Related Publications (2)

• Atmar RL, Baehner F, Cramer JP, Lloyd E, Sherwood J, Borkowski A, Mendelman PM; NOR-201 Study Group. Persistence of Antibodies to 2 Virus-Like Particle Norovirus Vaccine Candidate Formulations in Healthy Adults: 1-Year Follow-up With Memory Probe Vaccination. J Infect Dis. 2019 Jul 19;220(4):603-614. doi: 10.1093/infdis/jiz170.

  PMID: 31001633 DERIVED

• Atmar RL, Baehner F, Cramer JP, Song E, Borkowski A, Mendelman PM; NOR-201 Study Group. Rapid Responses to 2 Virus-Like Particle Norovirus Vaccine Candidate Formulations in Healthy Adults: A Randomized Controlled Trial. J Infect Dis. 2016 Sep 15;214(6):845-53. doi: 10.1093/infdis/jiw259. Epub 2016 Jun 28.

  PMID: 27354368 DERIVED

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: May 9, 2014
• First Posted: May 20, 2014
• Study Start: May 15, 2014
• Primary Completion: January 6, 2016
• Study Completion: January 6, 2016
• Last Updated: August 21, 2017
• Results First Posted: February 23, 2017

Record last verified: 2017-08

Locations

US (10)