Bivalent Norovirus Vaccine Study

NCT ID: NCT01168401

Last Updated: 2018-11-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 102 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-09-03
• Study Completion Date: 2013-01-09

Brief Summary

Randomized, multi-site, dose-escalation study of the safety and immunogenicity of four dosage levels of Intramuscular (IM) Norovirus Bivalent VLP Vaccine adjuvanted with MPL and Al(OH)3 compared to controls. Participants will receive two doses, by IM injection, 28 days apart.

The hypotheses for this study are:

• The incidence of adverse events after vaccination with IM Norovirus Bivalent VLP Vaccine will be similar to the incidence of adverse events after other IM vaccines including CERVARIX® which contains MPL and Al(OH)3.
• Two doses of IM Norovirus Bivalent VLP Vaccine will be more immunogenic than one dose.
• The post-vaccination serum antibody responses, the number of antibody secreting cells (ASC), including homing markers, and memory B-cell responses directed against norovirus antigens will be increased after IM Norovirus Bivalent VLP Vaccine compared to controls.

Conditions

Gastroenteritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

NoV GI.1/GII.4 Bivalent VLP Vaccine

Norovirus Bivalent GI.1 and GII.4 VLP Vaccine, adjuvanted with 50 microgram (mcg) MPL and 500 mcg Al(OH)3, IM, on Days 0 and 28.

Group Type: EXPERIMENTAL

NoV GI.1/GII.4 Bivalent VLP Vaccine

Intervention Type: BIOLOGICAL

2 Doses 28 days apart Cohort A: 18-49 Years

Cohort A1: IM Norovirus Bivalent GI.1/GII.4 VLP Vaccine (5/5 mcg)

Cohort A2: IM Norovirus Bivalent GI.1/GII.4 VLP Vaccine (15/15 mcg)

Cohort A3: IM Norovirus Bivalent GI.1/GII.4 VLP Vaccine (50/50 mcg)

Cohort A4: IM Norovirus Bivalent GI.1/GII.4 VLP Vaccine (150/150 mcg)

Cohort B: 50-64 Years IM Norovirus Bivalent GI.1/GII.4 VLP Vaccine (50/50 mcg)

Cohort C: 65-85 Years IM Norovirus Bivalent GI.1/GII.4 VLP Vaccine (50/50 mcg)

Cohort D: 18-49 Years IM Norovirus Bivalent GI.1/GII.4 VLP Vaccine (50/50 mcg)

Saline

Group Type: PLACEBO_COMPARATOR

Saline

Intervention Type: BIOLOGICAL

Two doses 28 days apart

Interventions

NoV GI.1/GII.4 Bivalent VLP Vaccine

2 Doses 28 days apart Cohort A: 18-49 Years

Cohort A1: IM Norovirus Bivalent GI.1/GII.4 VLP Vaccine (5/5 mcg)

Cohort A2: IM Norovirus Bivalent GI.1/GII.4 VLP Vaccine (15/15 mcg)

Cohort A3: IM Norovirus Bivalent GI.1/GII.4 VLP Vaccine (50/50 mcg)

Cohort A4: IM Norovirus Bivalent GI.1/GII.4 VLP Vaccine (150/150 mcg)

Cohort B: 50-64 Years IM Norovirus Bivalent GI.1/GII.4 VLP Vaccine (50/50 mcg)

Cohort C: 65-85 Years IM Norovirus Bivalent GI.1/GII.4 VLP Vaccine (50/50 mcg)

Cohort D: 18-49 Years IM Norovirus Bivalent GI.1/GII.4 VLP Vaccine (50/50 mcg)

Intervention Type: BIOLOGICAL

Saline

Two doses 28 days apart

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. Signed written informed consent.

2. Age:

• Cohort A: 18-49 years, inclusive
• Cohort B: 50-64 years, inclusive
• Cohort C: 65-85 years, inclusive
• Cohort D: 18-49 years, inclusive

3. Health Status:

• Cohort A and D: In good health as determined by a screening evaluation that includes vital signs, medical history, and physical exam within 45 days before administration of IM Norovirus Bivalent VLP Vaccine or control.
• Cohorts B and C: In good health as determined by a screening evaluation that includes vital signs, medical history, and physical exam within 45 days before administration of IM Norovirus Bivalent VLP Vaccine or control. Any existing medical diagnoses or conditions must be stable based on medical history and targeted physical examination. A stable medical condition is defined as: (A) Clinically acceptable health outcomes for the specific condition over the prior 6 months and (B) No change in prescription medication(s), dose, or frequency over the prior 3 months. Acceptable changes in medications are: a change of health care provider or insurance company or that is made for financial reasons as long as the medications are in the same class and/or a change due to improvement in a disease outcome.

4. Expressed interest and availability to fulfill the study requirements.

5. Female participants must be of non-childbearing potential (surgically sterile or post-menopausal for greater than or equal to [>=] 12 months), or if of childbearing potential (as determined by the investigator) must be practicing abstinence or using an effective licensed method of birth control (example 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 for at least 60 days after the last vaccination. A woman is eligible if she is monogamous with a male who has had a vasectomy. Male participants must agree not to father a child for at least 60 days after the last vaccination and to practice abstinence or use an effective method of birth control as noted above.

6. Agrees not to participate in another clinical trial with an investigational product for the entire duration of the study one year after the last study dose that is 393 days.

7. Agrees to storage of unused clinical specimens for an indefinite period of time for future norovirus research or research on other gastrointestinal pathogens.

3. Allergies or hypersensitivity to any component of the vaccine including MPL and Al(OH)3 adjuvants.

4. Any clinically significant abnormality detected on physical examination, including:

• Murmur (other than a functional murmur)
• Focal neurological abnormality
• Hepatosplenomegaly
• Lymphadenopathy
• Jaundice

5. Hypertension (Blood Pressure [BP] greater than [>] 140/90 millimeter of mercury [mm Hg] on two separate days)

6. Any lab abnormality (per the site local laboratory), as listed below:

• Absolute Neutrophil Count (ANC) outside the normal range (may be repeated if outside this limit)
• Total white blood cells (WBC) outside the normal range (may be repeated if outside this limit)
• Hemoglobin outside the normal range (may be repeated if outside this limit)
• Platelet count outside the normal range (may be repeated if outside this limit)
• Blood urea nitrogen (BUN) > upper limit of normal (ULN) (may be repeated if outside this limit)
• Creatinine > ULN (may be repeated if outside this limit)
• Glucose (fasting or random) outside the normal range (may be repeated if outside this limit)
• Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) > ULN (may be repeated if outside this limit)

7. Positive serology for hepatitis C or Human Immunodeficiency Virus (HIV) antibody or hepatitis B surface antigen.

8. For women of child bearing potential, positive serum pregnancy test within 14 days and urine pregnancy test within 24 hours of administering either dose of IM Norovirus Bivalent VLP Vaccine or control.

9. Nursing mother.

10. Temperature >100.4 degree Fahrenheit (F) or symptoms of an acute self-limited illness such as an upper respiratory infection or gastroenteritis within 3 days of administration of IM Norovirus Bivalent VLP Vaccine or control.

11. Previous participation in a Norovirus vaccine or challenge study.

12. Study site personnel or their family members.

13. Significant history of psychiatric hospitalization, alcohol abuse, or illicit drug use in the prior 5 years.

14. Completion of an investigational vaccine or drug study within 28 days before administration of IM Norovirus Bivalent VLP Vaccine or control.

15. Have a history of receiving immunoglobulin or other blood product within the 3 months prior to vaccination in this study.

16. Other condition that in the clinical judgment of the investigator would jeopardize the safety or rights of a participant participating in the trial, would render the participant unable to comply with the protocol or would interfere with the evaluation of the vaccine.

Exclusion Criteria

1. History of any of the following medical illnesses:

• Diabetes
• Cancer (malignancy other than resolved/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 less than [<] 5 years old)
• Recurrent infections (more than 3 hospitalizations for invasive bacterial infections such as pneumonia or meningitis)
• Any condition associated with immunodeficiency or participants taking immunosuppressant medication
• Neuroinflamatory or auto-immune disease

2. Any current illness requiring daily medication other than the following:

• Cohort A and D: Vitamins, birth control, anti-hypertensive medication, antihistamines or anti-depressant medication. The Principal Investigator (PI) should consult with the Central Safety Monitor and/or the sponsor for any clarification of medications allowable.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Navy Medical Research Center

Silver Springs, Maryland, United States

Saint Louis University

St Louis, Missouri, United States

University of Rochester Medical Center

Rochester, New York, United States

Countries

United States

References

Ramani S, Neill FH, Ferreira J, Treanor JJ, Frey SE, Topham DJ, Goodwin RR, Borkowski A, Baehner F, Mendelman PM, Estes MK, Atmar RL. B-Cell Responses to Intramuscular Administration of a Bivalent Virus-Like Particle Human Norovirus Vaccine. Clin Vaccine Immunol. 2017 May 5;24(5):e00571-16. doi: 10.1128/CVI.00571-16. Print 2017 May.

Reference Type: DERIVED

PMID: 28249841 (View on PubMed)

Lindesmith LC, Ferris MT, Mullan CW, Ferreira J, Debbink K, Swanstrom J, Richardson C, Goodwin RR, Baehner F, Mendelman PM, Bargatze RF, Baric RS. Broad blockade antibody responses in human volunteers after immunization with a multivalent norovirus VLP candidate vaccine: immunological analyses from a phase I clinical trial. PLoS Med. 2015 Mar 24;12(3):e1001807. doi: 10.1371/journal.pmed.1001807. eCollection 2015 Mar.

Reference Type: DERIVED

PMID: 25803642 (View on PubMed)

Treanor JJ, Atmar RL, Frey SE, Gormley R, Chen WH, Ferreira J, Goodwin R, Borkowski A, Clemens R, Mendelman PM. A novel intramuscular bivalent norovirus virus-like particle vaccine candidate--reactogenicity, safety, and immunogenicity in a phase 1 trial in healthy adults. J Infect Dis. 2014 Dec 1;210(11):1763-71. doi: 10.1093/infdis/jiu337. Epub 2014 Jun 20.

Reference Type: DERIVED

PMID: 24951828 (View on PubMed)

Other Identifiers

U1111-1187-1052

Identifier Type: REGISTRY

Identifier Source: secondary_id

LV03-104

Identifier Type: -

Identifier Source: org_study_id