Bivalent Norovirus Vaccine Study

NCT01168401 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: LV03-104U1111-1187-1052
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 3

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

Keywords

Vaccine, norovirus, acute gastroenteritis

Outcome Measures

Primary Outcomes (8)

• Number of Participants With Solicited Local Adverse Events (AEs) Post Dose 1

  The solicited local adverse events were reported using a memory aid. Pain was scaled as Mild (did not interfere with activity); Moderate (repeated use of non-narcotic pain reliever greater than (\>) 24 hours \[24h\] or interfered with activity); and Severe (any use of narcotic pain reliever or prevented daily activity). Tenderness was scaled as Mild (mild discomfort to touch); Moderate (discomfort with movement); and Severe (significant discomfort at rest). Swelling and redness were scaled as Mild (2.5-5 centimeter \[cm\] and did not interfere with activity); Moderate (5.1-10 cm or interfered with activity); and Severe (\>10 cm or prevented daily activity).

  Day 0 up to Day 7

• Number of Participants With Solicited Local AEs Post Dose 2

  The solicited local adverse events were reported using a memory aid. Pain was scaled as Mild (did not interfered with activity); Moderate (repeated use of non-narcotic pain reliever \>24h or interfered with activity); and Severe (any use of narcotic pain reliever or prevented daily activity). Tenderness was scaled as Mild (mild discomfort to touch); Moderate (discomfort with movement); and Severe (significant discomfort at rest). Swelling and redness were scaled as Mild (2.5-5 cm and did not interfere with activity); Moderate (5.1-10 cm or interfered with activity); and Severe (\>10 cm or prevented daily activity).

  Day 28 up to Day 35

• Number of Participants With Solicited Systemic AEs Post Dose 1

  Elevated oral temperature:Mild(38-38.4 Celsius\[C\]);Moderate(38.5-38.9 C);Severe(39-40 C).Headache:Mild(no interference with activity);Moderate(repeated use of non-narcotic pain reliever\>24h/some interference with activity);Severe(significant;any use of narcotic pain reliever/prevented daily activity).Fatigue,Malaise:Mild(no interference with activity);Moderate(some interference with activity);Severe(significant;prevented daily activity).Diarrhea:Mild(2-3loose stools/\<400gram\[g\]/24h);Moderate(4-5stools/400-800g/24h);Severe(\>=6watery stools/\>800g/24h/required intravenous\[IV\]hydration).Nausea/Vomiting:Mild(no interference with activity/1-2 episodes/24h);Moderate(some interference with activity/\>2 episodes/24h);Severe(prevented daily activity,required IV hydration).Muscle ache,chills,joint ache,abdominal cramp/pain:Mild(no interference with activity);Moderate(some interference with activity,not required medical intervention);Severe(prevented daily activity,required medical intervention).

  Day 0 up to Day 7

• Number of Participants With Solicited Systemic AEs Post Dose 2

  Elevated oral temperature:Mild(38-38.4 C);Moderate(38.5-38.9 C);Severe(39-40 C).Headache:Mild(no interference with activity);Moderate(repeated use of non-narcotic pain reliever\>24h/some interference with activity);Severe(significant;any use of narcotic pain reliever/prevented daily activity).Fatigue,Malaise:Mild(no interference with activity);Moderate(some interference with activity);Severe(significant;prevented daily activity).Diarrhea:Mild(2-3loose stools/\<400g/24h);Moderate(4-5stools/400-800g/24h);Severe(\>=6watery stools/\>800g/24h/required IV hydration).Nausea/Vomiting:Mild(no interference with activity/1-2 episodes/24h);Moderate(some interference with activity/\>2 episodes/24h);Severe(prevented daily activity,required IV hydration).Muscle ache,chills,joint ache,abdominal cramp/pain:Mild(no interference with activity);Moderate(some interference with activity,not required medical intervention);Severe(prevented daily activity,required medical intervention).

  Day 28 up to Day 35

• Number of Participants With Unsolicited AEs Post Dose 1

  Baseline up to Day 28 (Pre-dose 2)

• Number of Participants With Unsolicited AEs Post Dose 2

  Day 28 up to Day 56 (Post dose 2)

• Number of Participants With Clinically Significant Change From Baseline in Markedly Abnormal Laboratory Values

  The number of participants with any markedly abnormal standard safety laboratory values (serum chemistry or hematology) collected throughout study.

  Baseline up to Day 35

• Number of Participants With Serious Adverse Events (SAEs), Onset of Significant New Medical Conditions, Including Adverse Events of Special Interest (AESI)

  Baseline up to 365 Days after post dose 2 (Day 393)

Secondary Outcomes (12)

• Geometric Mean Titer (GMT) of Serum Anti-norovirus GI.1 and GII.4 VLP Ig (Immunoglobulin) A

  First (I) run: predose 1 and 7, 21, 28 days postdose (PD)1, and 7 and 28 days PD2; second (II) run: predose 1 and 28, 152 and 365 days PD2 (up to Day 393)

• GMT of Serum Anti-norovirus GI.1 and GII.4 VLP IgG

  I run: predose 1 and 7, 21, 28 days PD1, and 7 and 28 days PD2; II run: predose 1 and 28, 152 and 365 days PD2 (up to Day 393)

• GMT of Serum Anti-norovirus GI.1 and GII.4 VLP IgM

  I run: predose 1 and 7, 21, 28 days PD1, and 7 and 28 days PD2; II run: predose 1 and 28, 152 and 365 days PD2 (up to Day 393)

• Geometric Mean Fold Rise (GMFR) of Serum Anti-norovirus GI.1 and GII.4 VLP IgA as Compared to Baseline

  I run: 7, 21, 28 days PD1, 7 and 28 days PD2; II run: 28, 152 and 365 days PD2 (up to Day 393)

• GMFR of Serum Anti-norovirus GI.1 and GII.4 VLP IgG as Compared to Baseline

  I run: 7, 21, 28 days PD1, 7 and 28 days PD2; II run: 28, 152 and 365 days PD2 (up to Day 393)

Study Arms (2)

NoV GI.1/GII.4 Bivalent VLP Vaccine

EXPERIMENTAL

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.

Biological: NoV GI.1/GII.4 Bivalent VLP Vaccine

Saline

PLACEBO COMPARATOR

Biological: Saline

Interventions

NoV GI.1/GII.4 Bivalent VLP Vaccine 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)

NoV GI.1/GII.4 Bivalent VLP Vaccine

Saline BIOLOGICAL

Two doses 28 days apart

Saline

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent.
• 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
• 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.
• Expressed interest and availability to fulfill the study requirements.
• 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.
• 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.
• Agrees to storage of unused clinical specimens for an indefinite period of time for future norovirus research or research on other gastrointestinal pathogens.

You may not qualify if:

• 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
• 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.
• Allergies or hypersensitivity to any component of the vaccine including MPL and Al(OH)3 adjuvants.
• Any clinically significant abnormality detected on physical examination, including:
• Murmur (other than a functional murmur)
• Focal neurological abnormality

Sponsors & Collaborators

• Takeda: lead

Study Sites (3)

Navy Medical Research Center

Silver Springs, Maryland, 20910, United States

Location

Saint Louis University

St Louis, Missouri, 63104, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Related Publications (3)

• 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.

  PMID: 28249841 DERIVED

• 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.

  PMID: 25803642 DERIVED

• 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.

  PMID: 24951828 DERIVED

MeSH Terms

Conditions

Gastroenteritis

Interventions

Sodium Chloride

Condition Hierarchy (Ancestors)

Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Takeda
• Organization: Medical Director

trialdisclosures@takeda.com

+1-877-825-3327

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2010
• First Posted: July 23, 2010
• Study Start: September 3, 2010
• Primary Completion: January 1, 2013
• Study Completion: January 9, 2013
• Last Updated: November 23, 2018
• Results First Posted: November 23, 2018

Record last verified: 2018-04

Locations

US (3)