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Norwalk Vaccine Study

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
LigoCyte Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT00973284
First received: September 8, 2009
Last updated: May 21, 2012
Last verified: July 2010

September 8, 2009
May 21, 2012
September 2009
March 2010   (final data collection date for primary outcome measure)
Evaluation of efficacy as determined by the illness rate of viral acute gastroenteritis (AGE) [ Time Frame: 7 days post challenge ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00973284 on ClinicalTrials.gov Archive Site
Evaluation of vaccine safety, as determined by the occurrence of local intranasal symptoms and other solicited symptoms, and unsolicited adverse events and the occurrence of SAEs for 180 days following the last study vaccination. [ Time Frame: 21 days post each dose for solicited symptoms and adverse events and 180 days for SAEs. ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
Norwalk Vaccine Study
Phase 1-2, Randomized, Multi-Center, Double-Blind, Placebo-Controlled, Safety and Efficacy Study in Healthy Adults of Intranasal Norwalk Virus-like Particle Vaccine in Experimental Human Norwalk Virus Infection

Randomized, double blind, multi-center, placebo-controlled safety and efficacy study in healthy adults of Norwalk VLP Vaccine in experimental human Norwalk Virus infection.

The study hypothesis is: Two doses of Norwalk VLP vaccine will be efficacious compared to placebo following an experimental oral challenge with live wild-type Norwalk Virus.

The study consists of two stages, the Vaccination Stage including post-vaccination follow-up followed by the Challenge Stage with post-challenge follow-up. Subjects will receive a two-dose regimen of Norwalk VLP Vaccine or placebo by intranasal administration on Days 0 and 21 and will be followed for vaccine safety and immune responses. On or after Study Day 42, subjects will be admitted to an inpatient nursing unit, challenged with live Norwalk Virus Lot 42399 by oral administration, remain in the unit for at least 4 days following challenge and then followed for post-challenge safety and efficacy with multiple clinical assessments and collection of blood and stool specimens.

Not Provided
Interventional
Phase 1
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
  • Acute Gastroenteritis
  • Norwalk Virus Infection
  • Biological: Norwalk VLP vaccine
    intranasal, two doses 21 days apart
  • Biological: mannitol and sucrose
    two doses 21 days apart
  • Experimental: 100 mcg Norwalk VLP Vaccine
    Intervention: Biological: Norwalk VLP vaccine
  • Placebo Comparator: Excipients
    manitol and sucrose
    Intervention: Biological: mannitol and sucrose
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
98
August 2010
March 2010   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Signed informed consents.
  2. Age 18 - 50 years, inclusive.
  3. Good general health as determined by a screening evaluation within 45 days of randomization.
  4. 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)
  5. Available to return for follow-up visits following discharge from the inpatient unit and deliver stool specimens to the investigator promptly.
  6. 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.
  7. 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.]
  8. 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).

Exclusion Criteria:

  1. 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.
  2. Nursing mother.
  3. Living with or having daily contact with childcare workers.
  4. 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.
  5. 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)].
  6. Any gastroenteritis within the past 2 weeks.
  7. 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.
  8. Regular use of medication other than oral contraceptive agents, anti-hypertensives, anti-depressants, vitamins and minerals.
  9. 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")
    • Seizures (other than febrile seizures as a child <5 years old)
    • Asthma requiring treatment with inhaler or medication in the prior 2 years
    • Neuro-inflammatory disease
    • Autoimmune disease
    • Eating disorder
    • Chronic headaches associated with vomiting
    • Chronic vomiting syndrome
  10. Any current illness requiring daily medication other than vitamins, minerals, birth control, anti-depressants or anti-hypertensives.
  11. Blood Type B or AB. [This blood test may be done outside of the 45 day window and does not need to be repeated.]
  12. Allergies or hypersensitivity to chitosan, shrimp, other shellfish or any component of the vaccine or placebo.
  13. History of nasal surgery of any type (including tonsillectomy or adenoidectomy).
  14. Any clinically significant abnormality detected on physical examination, including:

    • Murmur (other than a functional murmur)
    • Focal neurological abnormality
    • Hepatosplenomegaly
    • Lymphadenopathy
    • Jaundice
  15. Hypertension defined as BP > 150/90 mm Hg on two separate measurements. Chronic stable well-controlled hypertension on medications is allowed.
  16. History of more than 3 hospitalizations for invasive bacterial infections (pneumonia, meningitis), acute or chronic dermatitis (e.g. eczema, seborrhea, psoriasis) or collagen vascular disease (e.g. SLE or dermatomyositis).
  17. Presence of other serious chronic illness (i.e. malignancy other than a resolved skin lesion).
  18. Positive stool/fecal culture for bacterial pathogens (salmonella, campylobacter, E. coli 0157:H7, and shigella) or positive stool/fecal screen for ova and parasites.
  19. Employment in the food service industry, such as restaurants, or cafeteria facilities. Specifically, this will include persons whose employment requires food processing in the 4 weeks following challenge.
  20. Health-care workers with patient contact expected in the 4 weeks following challenge.
  21. Expected contact (through employment or at home) with immunocompromised persons (HIV-positive, receiving immunosuppressive medications such as oral steroids, anti-neoplastic agents) in the 4 weeks following challenge.
  22. Employment as an airline flight attendant, scheduled to work in the 4 weeks following challenge.
  23. Persons planning on taking a cruise in the 4 weeks following challenge.
  24. Persons who have consumed or plan to consume raw shellfish (e.g. oysters) within 7 days prior to enrollment or throughout the study.
  25. Any of the following lab abnormalities:

    • Absolute neutrophil count (ANC) or total WBC outside the normal range (may be repeated once if outside this limit)
    • Hemoglobin outside the normal range (may be repeated once if outside this limit)
    • Platelet count outside the normal range (may be repeated once if outside this limit)
    • Electrolytes, BUN and/or creatinine outside the normal range (may be repeated once if outside this limit)
    • Glucose > upper limit of normal (ULN) (may be repeated once if outside this limit). Fasting glucose is not required.
    • ALT, AST, alkaline phosphatase, bilirubin (total and indirect) or GGT outside the normal range (may be repeated once if outside this limit)
    • Positive serology for hepatitis C or HIV antibody or hepatitis B surface antigen or RPR
  26. For women, positive serum pregnancy test within 14 days or positive urine pregnancy test within 24 hours of randomization.
  27. Temperature > 99.7°F orally or symptoms of an acute self-limited illness such as an upper respiratory infection or gastroenteritis within 3 days of randomization.
  28. Previous participation in a study of experimental norovirus infection or vaccines.
  29. Study site personnel or their family members.
  30. Significant history of psychiatric hospitalization, alcohol abuse, or illicit drug use.
  31. Receipt of a licensed live vaccine within 28 days or a licensed inactivated vaccine within 14 days of randomization.
  32. Completion of an investigational vaccine or drug study within 28 days of randomization.
  33. Other condition that in the clinical judgment of the investigator would jeopardize the safety or rights of a subject participating in the trial, would render the subject unable to comply with the protocol or would interfere with the evaluation of the vaccination stage or the evaluation of the challenge stage.
Both
18 Years to 50 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00973284
LV01-103
Yes
LigoCyte Pharmaceuticals, Inc.
LigoCyte Pharmaceuticals, Inc.
Not Provided
Principal Investigator: 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.
LigoCyte Pharmaceuticals, Inc.
July 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP