Norovirus Bivalent-Vaccine Efficacy Study
This study has been completed.
Information provided by (Responsible Party):
LigoCyte Pharmaceuticals, Inc.
First received: May 25, 2012
Last updated: May 9, 2014
Last verified: May 2014
The purpose of this study is to determine whether the norovirus vaccine is effective in preventing acute gastroenteritis due to the experimental human Norovirus GII.4 challenge dose. The purpose is also to evaluate the safety of the vaccine and the immunogenicity of the vaccine.
Prevention From Norovirus Infection
Biological: Norovirus Bivalent Vaccine
Biological: Saline Comparator
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
||Phase 1-2, Randomized, Multi-Center, Double-Blind, Placebo-Controlled, Safety, Immunogenicity, and Efficacy Study in Healthy Adults of Intramuscular Norovirus Bivalent Virus-like Particle Vaccine in Experimental Human Norovirus GII.4 Disease
Primary Outcome Measures:
Secondary Outcome Measures:
- Evaluation of Efficacy [ Time Frame: 30 days post challenge ] [ Designated as safety issue: Yes ]
Infection rate of the GII.4 strain, Severity of viral AGE , Detection of GII.4 norovirus positive RT-PCR in the stool,Seroresponse rate (4-fold rise) pre-challenge Day 0 to post-challenge Day 30, Correlation of GII.4 serum antibodies prior to challenge with protection from GII.4 illness,
| Study Start Date:
| Study Completion Date:
| Primary Completion Date:
||February 2014 (Final data collection date for primary outcome measure)
Experimental: Norovirus Bivalent VLP Vaccine
2 doses Norovirus Bivalent VLP Vaccine (50 mcg of GI.1 Norwalk VLP and 50 mcg of GII.4 cVLP)
Biological: Norovirus Bivalent Vaccine
2 doses IM 28 days apart
Placebo Comparator: Saline
normal saline for injection (0.9% NaCl and preservative-free)
Biological: Saline Comparator
2 doses IM 28 days apart
|Ages Eligible for Study:
||18 Years to 49 Years
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
To be eligible to participate in this study, a subject must meet the following criteria:
- Signed informed consent.
- Age 18 to 50 years (e.g., not reached their 50th birthday).
- 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 Norovirus contamination of the environment and spread of infection and illness to the community. The prospective subjects must pass (≥70 % correct answers) a written examination on all aspects of the study before enrollment.
- Available to return for follow-up visits following discharge from the inpatient unit and able to deliver stool specimens to the investigative site promptly with no plan to move within the duration of the study.
- 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 from the day of vaccination until 60 days after the Challenge visit.
- Have a serum antibody titer of ≤1:1600 to the GII.4 Norovirus challenge strain as measured by IgG P Particle ELISA.
- Demonstrated to be H Type 1 secretor positive by HBGA binding assay of their saliva test. [This saliva test may be done at anytime prior to enrollment and does not need to be repeated.]
- Negative serology for hepatitis C antibody, HIV antibody, hepatitis B surface antigen, and RPR.
- Agrees not to participate in another clinical trial with an investigational product for the duration of the study (12 months after the last dose of study vaccine or placebo i.e. 393 days).
To be eligible to participate in this study, a subject must NOT meet any of the following criteria:
- 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.
- History of any gastroenteritis suggestive of Norovirus illness since screening serum antibody IgG P Particle ELISA testing was done.
- History of 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, malabsorption, maldigestion, major GI surgery, or diverticulitis anytime during the subject's lifetime or any other chronic GI disorders that would interfere with interpretation of symptoms or evaluation during the study.
- Routine use of medication other than oral contraceptive agents, anti-hypertensives, anti-depressants, vitamins and minerals. The use of any other medications should be discussed with the Sponsor and/or CSM.
History of any of the following medical illnesses:
- Immunosuppression (disease or treatments that may affect immune system function)
- Diabetes (including gestational diabetes during the pregnancy that required treatment other than dietary).
- Cancer (malignancy other than a resolved or excised 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 past 2 years.
- Neuro-inflammatory disease
- Autoimmune disease
- Eating disorder
- Chronic headaches associated with vomiting
- Chronic vomiting syndrome
- Any current illness requiring daily medication other than vitamins, minerals, birth control, anti-hypertensives or anti-depressants. The use of any other medications should be discussed with the Sponsor and/or CSM.
- Allergies or hypersensitivity to any component of the vaccine or challenge virus.
Any clinically significant abnormality detected on physical examination, including:
- Murmur (other than a functional, ie normal, murmur)
- Focal neurological abnormality
- Hypertension defined as BP > 150/90 mm Hg on two separate measurements. Chronic stable well-controlled hypertension on medications is allowed.
- History of 3 or more 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).
- Presence of serious chronic illness.
- Positive stool/fecal culture for bacterial pathogens (salmonella, campylobacter, E. coli 0157:H7, yersinia, or shigella) or positive stool/fecal screen for ova and parasites.
- 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.
- Health-care workers with patient contact expected in the 4 weeks following challenge.
- Expected contact (through employment or at home) with immunocompromised persons (HIV-positive, receiving immunosuppressive medications such as oral steroids or anti-neoplastic agents) in the 4 weeks following challenge.
- Employment as an airline flight attendant scheduled to work in the 4 weeks following challenge.
- Persons planning on taking a cruise in the 4 weeks following challenge.
- Persons who plan to be living in a confined environment (e.g. ship, camp, or dormitory) within 4 weeks following challenge.
- Persons who have consumed or plan to consume raw shellfish (e.g. oysters) from screening through post challenge Day 30.
Any of the following lab abnormalities (per the site local laboratory):
- Absolute neutrophil count (ANC) outside the normal range
- Total WBC outside the normal range
- Hemoglobin or hematocrit outside the normal range
- Platelet count outside the normal range
- Electrolytes (Na, K, Cl, CO2), BUN and/or creatinine outside the normal range
- Screening glucose > upper limit of normal (ULN). Fasting glucose is not required
- ALT, AST, alkaline phosphatase, bilirubin (total and indirect), or GGT outside the upper limit of the normal range
- Screening urinalysis with a value higher than "trace" positive for urine protein or urine glucose, or urine RBCs (≥3; other than women during menses).
All of the above labs may be repeated if outside the normal limits. If repeated and continue outside site normal ranges, may enroll if determined by the PI to be not clinically significant and discussed with the Sponsor and/or CSM.
- For women of child bearing potential, positive serum pregnancy test within 14 days or positive urine pregnancy test within one day of randomization.
- Temperature > 100.4°F orally, or symptoms of an acute self-limited illness such as an upper respiratory infection within 3 days of administering either dose of Norovirus Bivalent VLP vaccine or placebo control or the challenge product.
- Resting heart rate >100 beats per minute or <55 beats per minute, respiratory rate ≥ 20 breaths per minute. If heart rate <55 beat per minute and the investigator determines that this is not clinically significant and heart rate increases > 55 beats per minute on moderate exercise, subject will not be excluded. Vital signs may be repeated.
- Clinically abnormal screening electrocardiogram (ECG) defined as pathologic Q waves and significant ST-T wave changes; criteria for left ventricular hypertrophy; and any non-sinus rhythm excluding isolated premature atrial contractions.
- Previous participation in a study of experimental norovirus infection or norovirus vaccine.
- Study site personnel or their family members
- Significant history of psychiatric hospitalization, alcohol abuse, or illicit drug use.
- Receipt of a licensed live vaccine within 28 days or a licensed inactivated vaccine within 14 days of administration of either dose of vaccine or placebo or the challenge product.
- Completion of an investigational vaccine or drug study within 7 days of randomization.
- Receipt of systemic corticosteroids for greater than 7 days within the past six months.
- Regular use of laxatives or anti-motility agents.
- Receipt of blood or blood products within the past six months.
- Subjects who are unwilling or unable to cease smoking from entry to the inpatient facility until discharge from the inpatient facility.
- 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.
Challenge Stage Exclusion Criteria
The following additional exclusion criteria must not be met prior to admission to the inpatient unit for Challenge:
- Use of antibiotics within the 7 days prior to entry into the inpatient challenge facility.
- Use of any H-2 receptor antagonists (e.g. Tagamet, Zantac, and Pepcid), proton pump inhibitors (e.g. Prilosec, Protonix, and Prevacid), or prescription acid suppression medication or over the counter antacids within 72 hours of the challenge.
- Use of prescription or OTC medications containing acetaminophen, aspirin, ibuprofen, and/or other non-steroidal anti-inflammatory drugs within 48 hours prior to challenge.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01609257
|Atlanta, Georgia, United States, 30322 |
|Baltimore, Maryland, United States, 21201 |
|University of Rochester Medical Center
|Rochester, New York, United States, 14642 |
|Cincinnati Children's Hospital
|Cincinnati, Ohio, United States, 45229 |
|Baylor College of Medicine
|Houston, Texas, United States, 77030 |
LigoCyte Pharmaceuticals, Inc.
||David Bernstein, MD
||Cincinatti Children's Hospital
||Mohamed S Al-Ibrahim, MB, ChB
||SNBL Clinical Pharmacology Center
||David Y Graham, MD
||Baylor College of Medicine
||Robert L Atmar, MD
||Children's Hospital Medical Center, Cincinnati
||G. Marshall Lyon, MD
||John J Treanor, MD
||University of Rochester
No publications provided by LigoCyte Pharmaceuticals, Inc.
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Bernstein DI, Atmar RL, Lyon GM, Treanor JJ, Chen WH, Jiang X, Vinjé J, Gregoricus N, Frenck RW Jr, Moe CL, Al-Ibrahim MS, Barrett J, Ferreira J, Estes MK, Graham DY, Goodwin R, Borkowski A, Clemens R, Mendelman PM. Norovirus vaccine against experimental human GII.4 virus illness: a challenge study in healthy adults. J Infect Dis. 2015 Mar 15;211(6):870-8. doi: 10.1093/infdis/jiu497. Epub 2014 Sep 9.
ClinicalTrials.gov processed this record on April 23, 2015
||LigoCyte Pharmaceuticals, Inc.
History of Changes
|Other Study ID Numbers:
|Study First Received:
||May 25, 2012
||May 9, 2014
||United States: Food and Drug Administration