Norwalk Vaccine Study

NCT00973284 | Completed Phase 1 DMC

• 2 other identifiers: LV01-103U1111-1176-0535
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study was to evaluate the efficacy of the Norwalk virus-like particle (VLP) vaccine as determined by the illness rate of viral acute gastroenteritis (AGE) during the inpatient stay.

Conditions

Acute Gastroenteritis; Norwalk Virus Infection

Keywords

Prevention of acute gastroenteritis due to infection with and experimental Norwalk Virus

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants with Viral Acute Gastroenteritis (AGE)

  Viral AGE was a composite endpoint for the analysis of clinical illness and was defined as meeting one or more definitions of Norwalk Virus Infection and one or more of the definitions of AGE. Norwalk Virus Infection: * PAN-Immunoglobulin (Ig) Enzyme Linked Immunosorbent Assay (ELISA) for anti-Norwalk Virus Antibody IgM, IgG and IgA, ≥4-fold rise in titer in serum on Challenge Day 30 compared to Pre-Challenge. * Reverse Transcription Polymerase Chain Reaction (RT-PCR), a single positive post-challenge stool sample. * Norwalk Virus Antigen, a single positive post-challenge stool sample. Acute Gastroenteritis: -\>200 grams of watery feces in 24-hour collection that immediately takes the shape of the container. * Vomiting and watery feces ≤200 grams on the same or consecutive days. * One vomiting episode plus one of the following symptoms: abdominal cramps or pains, nausea, bloating, loose feces, fever ≥99.7° Fahrenheit, or myalgia on the same or consecutive days.

  7 Days Post-Challenge

Secondary Outcomes (18)

• Percentage of Participants with Norwalk Virus Infection Anytime Post Challenge

  Up to 30 Days Post-Challenge

• Severity of Viral AGE using the Modified Vesikari Scale

  Up to 30 Days Post-Challenge

• Duration of Viral AGE Among Challenged Participants

  Up to 30 Days Post-Challenge

• Percentage of Participants with Norwalk Virus Antigen Detected in the Stool

  Days 1 thru 4, 7, 21 and 30 in the Challenge Stage

• Percentage of Participants with Seroconversion in Serum Anti-Norwalk Virus

  Pre-Challenge to 30 Days Post-Challenge

Study Arms (2)

Norwalk VLP Vaccine 100 µg

EXPERIMENTAL

Norwalk Virus-like Particle (VLP) Vaccine 100 µg, dry powder, intranasally using a delivery device with a puff of air, 50 µg in each nostril, on Days 0 and 21 in the Vaccination Stage. Norwalk Virus, 48 Reverse Transcription Polymerase Chain Reaction (RT-PCR) units, solution, orally, on Day 42 in the Challenge Stage.

Biological: Norwalk VLP vaccine; Biological: Norwalk virus

Placebo

PLACEBO COMPARATOR

Norwalk VLP placebo-matching vaccine, dry powder, intranasally using a delivery device with a puff of air, 50 µg in each nostril, on Days 0 and 21 in the Vaccination Stage. Norwalk Virus, 48 RT-PCR units, solution, orally, on Day 42 in the Challenge Stage.

Biological: mannitol and sucrose; Biological: Norwalk virus

Interventions

Norwalk VLP vaccine BIOLOGICAL

Norwalk VLP vaccine dry powder

Norwalk VLP Vaccine 100 µg

mannitol and sucrose BIOLOGICAL

Mannitol and sucrose as placebo-matching Norwalk VLP Vaccine dry powder

Placebo

Norwalk virus BIOLOGICAL

Norwalk virus solution

Norwalk VLP Vaccine 100 µg; Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Signed informed consents.
• Age 18 - 50 years, inclusive.
• Good general health as determined by a screening evaluation within 45 days of randomization.
• Expressed interest, availability, and understanding to fulfill the study requirements including measures to prevent Norwalk virus contamination of the environment and spread of infection and illness to the community. The prospective subjects must pass (\> 75 % correct answers) a written examination on all aspects of the study before enrollment. (Appendix D)
• Available to return for follow-up visits following discharge from the inpatient unit and deliver stool specimens to the investigator promptly.
• Female subjects must be of non-childbearing potential, or if of childbearing potential (as determined by the investigator) must be practicing abstinence or using an effective licensed method of birth control (e.g. oral contraceptives; diaphragm or condom in combination with contraceptive jelly, cream, or foam; intrauterine contraceptive device, or Depo-Provera; skin patch; vaginal ring or cervical cap) for 30 days prior to vaccination and must agree to continue such precautions during the study and for 60 days after the Challenge visit. Male subjects must agree not to father a child during the study and for 60 days after the Challenge visit.
• Demonstrated to be H type-1 antigen secretor positive (by saliva test). \[This saliva test may be done outside of the 45 day window and does not need to be repeated.\]
• Agrees not to participate in another clinical trial with an investigational product for the entire duration of the study (six months after the last dose of study vaccine or placebo i.e. 201 days).

You may not qualify if:

• Living with or having daily contact with children age 5 years or less or a woman known to be pregnant. This includes significant contact at home, school, day-care, or equivalent facilities.
• Nursing mother.
• Living with or having daily contact with childcare workers.
• Living with or having daily contact with elderly persons aged 70 years or more, or infirmed, diapered individuals, persons with disabilities or incontinent persons. This includes work or visits to nursing homes and day-care or equivalent facilities.
• Evidence of recent (within 2 months) or of current nonbacterial gastroenteritis suggestive of Norwalk virus infection \[vomiting or unformed or watery stools ( \> 2 during a 24 hour period)\].
• Any gastroenteritis within the past 2 weeks.
• History of chronic functional dyspepsia, chronic gastroesophageal reflux disease, peptic ulcer disease, gastrointestinal hemorrhage, gall bladder disease, inflammatory bowel disease, irritable bowel syndrome, frequent diarrhea, chronic constipation, or diverticulitis anytime during the subject's lifetime.
• Regular use of medication other than oral contraceptive agents, anti-hypertensives, anti-depressants, vitamins and minerals.
• History of any of the following medical illnesses:
• Chronic rhinitis, runny nose, sneezing (including seasonal allergies)
• Clinically significant nose bleed within the prior 12 months
• Diabetes
• Cancer (malignancies other than a resolved skin lesion)
• Heart disease (hospitalization for a heart attack, arrhythmia, or syncope)
• Unconsciousness (other than a single brief "concussion")

Sponsors & Collaborators

• Takeda: lead

Study Sites (3)

SNBL

Baltimore, Maryland, 21201, United States

Location

Cincinnati Childrens Hospital Medical Center

Cincinnati, Ohio, 45206, United States

Location

Baylor College of Medicine

Houston, Texas, 77030-3498, United States

Location

Related Publications (1)

• Atmar RL, Bernstein DI, Harro CD, Al-Ibrahim MS, Chen WH, Ferreira J, Estes MK, Graham DY, Opekun AR, Richardson C, Mendelman PM. Norovirus vaccine against experimental human Norwalk Virus illness. N Engl J Med. 2011 Dec 8;365(23):2178-87. doi: 10.1056/NEJMoa1101245.

  PMID: 22150036 DERIVED

MeSH Terms

Interventions

Mannitol; Sucrose

Intervention Hierarchy (Ancestors)

Sugar Alcohols; Alcohols; Organic Chemicals; Carbohydrates; Disaccharides; Oligosaccharides; Polysaccharides; Sugars

Study Officials

• Robert L Atmar, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

• David I Bernstein, MD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

• Clayton D Harro, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

• Mohamed S Al-Ibrahim, MD

  SNBL Clinical Pharmacology Center, Inc.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• 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: September 8, 2009
• First Posted: September 9, 2009
• Study Start: August 4, 2009
• Primary Completion: April 7, 2010
• Study Completion: August 18, 2010
• Last Updated: August 8, 2017

Record last verified: 2017-08

Locations

US (3)