Trial record 2 of 53 for:    H7N9 influenza | Vaccine | NIH

A Phase I Study Priming With an Inactivated A/H7N9 Influenza Virus Vaccine With or Without MF59 Adjuvant Followed by Live Attenuated A/H7N9 Influenza Virus Vaccine

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified September 2014 by National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT02251288
First received: September 25, 2014
Last updated: NA
Last verified: September 2014
History: No changes posted
  Purpose

A phase I prospective, randomized study in healthy adult subjects at a single center. Adult subjects age 18 to 47 years and meeting all enrollment criteria will choose to participate as subjects who receive inactivated vaccine followed by a live vaccine boost at 4 weeks (Group 1), 12 weeks (Group 2), or 24 weeks (Group 3), or to be in an observational group (Group 4) which will not be scheduled for a booster dose but will serve as a backup for dropouts in the other three groups. A fifth group will receive two intramuscular doses of adjuvanted H7N9 pIIV separated by four weeks.


Condition Intervention Phase
Avian Influenza
Drug: MF59 Adjuvant
Biological: A/H7N9 pIIV Vaccine
Biological: H7N9 pLAIV Vaccine
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Phase I Randomized Study in Healthy Adults to Assess the Safety, Reactogenicity and Immunogenicity of Priming With an Inactivated A/H7N9 Influenza Virus Vaccine With or Without MF59 Adjuvant Followed by Live Attenuated A/H7N9 Influenza Virus Vaccine

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Occurrence of solicited vaccination site and systemic reactogenicity on the day of each study vaccination through 7 days after each study vaccination. [ Time Frame: On the day of each study vaccination through 7 days after each study vaccination ] [ Designated as safety issue: Yes ]
  • Percentage of subjects achieving seroconversion defined as either a pre-vaccination HAI titer <1:10 and a post-vaccination HAI titer >/1:40 or a pre-vaccination HAI titer >/1:10 and a minimum four-fold rise in post-vaccination HAI antibody titer [ Time Frame: 28 days after the second study vaccination ] [ Designated as safety issue: No ]
  • Occurrence of study vaccine-related serious adverse events from the time of the first study vaccination through approximately 12 months after the last study vaccination. [ Time Frame: Day 1 through approximately 12 months after the last study vaccination ] [ Designated as safety issue: Yes ]
  • Percentage of subjects shedding vaccine virus as detected by rRT-PCR after administration of pLAIV [ Time Frame: Day 27 through Day 178 ] [ Designated as safety issue: No ]
  • Percentage of subjects achieving a serum HAI antibody titer of 1:40 or greater against the H7N9 antigen contained in the study vaccines at approximately 28 days after the second study vaccination [ Time Frame: Approximately 28 days after the second study vaccination ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Occurrence of new-onset chronic medical conditions through 6 months after the last study vaccination [ Time Frame: Day 169 through 6 months after the last study vaccination ] [ Designated as safety issue: Yes ]
  • Percentage of subjects achieving seroconversion (defined as either a pre-vaccination HAI titer <1:10 and a post-vaccination HAI titer>/1:40 or a pre-vaccination HAI titer >/1:10 and a minimum four-fold rise in post-vaccination HAI antibody titer) [ Time Frame: Approximately 28 days after the first study vaccination, and 56 and 180 days after the second study vaccination ] [ Designated as safety issue: No ]
  • Percentage of subjects achieving seroconversion defined as either a pre-vaccination neutralizing antibody (NtAb) titer <1:10 and a post-vaccination NtAb titer>/1:40 or pre-vaccination NtAb titer >/1:10 and a min. four-fold rise in post-vaccination NtAb [ Time Frame: Approximately 28 days after each study vaccination and 56 and 180 days after the last vaccination ] [ Designated as safety issue: No ]
  • Percentage of subjects achieving a serum NtAb titer of 1:40 or greater against the H7N9 antigen contained in the study vaccines at baseline and at approximately 28 days after each study vaccination and 56 and 180 days after the second vaccination [ Time Frame: Baseline and at approximately 28 days after each study vaccination and 56 and 180 days after the second vaccination ] [ Designated as safety issue: No ]
  • Occurrence of unsolicited non-serious adverse events 28 days after each study vaccination [ Time Frame: 28 days after each study vaccination ] [ Designated as safety issue: Yes ]
  • Percentage of subjects achieving a serum HAI antibody titer of 1:40 or greater against the H7N9 antigen contained in the study vaccine at baseline and at approximately 28 days after the first study vaccination, and 56 and 180 days after the second study [ Time Frame: Baseline and 28 days after the first study vaccination and 56 and 180 days after the second study vaccination ] [ Designated as safety issue: No ]
  • Geometric mean titers of serum HAI and NtAb antibody at baseline and at approximately 28 days after each study vaccination [ Time Frame: Baseline and at approximately 28 days after each study vaccination ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 4
8 patients receive A/H7N9 15 mcg IM on Day 1, 8 patients receive A/H7N9 15 mcg plus MF59 adjuvant IM on Day 1
Drug: MF59 Adjuvant
Novartis supplies the MF59 adjuvant as an oil-in-water milky emulsion in single-use vials containing a fill volume of 0.7 mL. Group 1 through Group 5 will receive MF59 IM on Day 1.
Biological: A/H7N9 pIIV Vaccine
Sanofi supplies the monovalent influenza A/H7N9 virus vaccine as a sterile, clear, and slightly opalescent suspension in single-dose vials containing 15 mcg HA per 0.5 mL. Group 1 through Group5 will receive the IM vaccine on Day 1
Experimental: Group 3
12 patients receive S A/H7N9 15 mcg IM on Day 1, 12 patients receive A/H7N9 15 mcg plus MF59 adjuvant IM on Day 1 and all receive single dose of IN sprayer 107 FFU H7 N9 pLAIV on Day 169
Drug: MF59 Adjuvant
Novartis supplies the MF59 adjuvant as an oil-in-water milky emulsion in single-use vials containing a fill volume of 0.7 mL. Group 1 through Group 5 will receive MF59 IM on Day 1.
Biological: A/H7N9 pIIV Vaccine
Sanofi supplies the monovalent influenza A/H7N9 virus vaccine as a sterile, clear, and slightly opalescent suspension in single-dose vials containing 15 mcg HA per 0.5 mL. Group 1 through Group5 will receive the IM vaccine on Day 1
Biological: H7N9 pLAIV Vaccine
MedImmune supplies pLAIV vaccines as a colorless to pale yellow and clear to slightly cloudy suspension in single, unit-dose, Becton-Dickinson Accuspray™ Nasal Spray Systems sprayer devices. Each filled sprayer device contains a 0.5 mL dose of 10^7FFU of H7N9 Anhui 2013/AA ca vaccine. Group I receives the IN dose on Day 29, Group 2 on Day 85, and Group 3 on Day 169.
Experimental: Group 2
12 patients receive A/H7N9 15 mcg IM on Day 1, 12 patients receive A/H7N9 15 mcg plus MF59 adjuvant IM on Day 1 and all receive single dose of IN sprayer107 FFU H7 N9 pLAIV on Day 85
Drug: MF59 Adjuvant
Novartis supplies the MF59 adjuvant as an oil-in-water milky emulsion in single-use vials containing a fill volume of 0.7 mL. Group 1 through Group 5 will receive MF59 IM on Day 1.
Biological: A/H7N9 pIIV Vaccine
Sanofi supplies the monovalent influenza A/H7N9 virus vaccine as a sterile, clear, and slightly opalescent suspension in single-dose vials containing 15 mcg HA per 0.5 mL. Group 1 through Group5 will receive the IM vaccine on Day 1
Biological: H7N9 pLAIV Vaccine
MedImmune supplies pLAIV vaccines as a colorless to pale yellow and clear to slightly cloudy suspension in single, unit-dose, Becton-Dickinson Accuspray™ Nasal Spray Systems sprayer devices. Each filled sprayer device contains a 0.5 mL dose of 10^7FFU of H7N9 Anhui 2013/AA ca vaccine. Group I receives the IN dose on Day 29, Group 2 on Day 85, and Group 3 on Day 169.
Experimental: Group 1
12 patients receive Intramuscular (IM) A/H7N9 15 mcg on Day 1, 12 patients receive A/H7N9 15 mcg plus MF59 adjuvant IM on Day 1 and all receive single dose of Intranasal (IN) sprayer 107 FFU H7 N9 pLAIV on Day 29
Drug: MF59 Adjuvant
Novartis supplies the MF59 adjuvant as an oil-in-water milky emulsion in single-use vials containing a fill volume of 0.7 mL. Group 1 through Group 5 will receive MF59 IM on Day 1.
Biological: A/H7N9 pIIV Vaccine
Sanofi supplies the monovalent influenza A/H7N9 virus vaccine as a sterile, clear, and slightly opalescent suspension in single-dose vials containing 15 mcg HA per 0.5 mL. Group 1 through Group5 will receive the IM vaccine on Day 1
Biological: H7N9 pLAIV Vaccine
MedImmune supplies pLAIV vaccines as a colorless to pale yellow and clear to slightly cloudy suspension in single, unit-dose, Becton-Dickinson Accuspray™ Nasal Spray Systems sprayer devices. Each filled sprayer device contains a 0.5 mL dose of 10^7FFU of H7N9 Anhui 2013/AA ca vaccine. Group I receives the IN dose on Day 29, Group 2 on Day 85, and Group 3 on Day 169.
Experimental: Group 5
12 patients receive A/H7N9 15 mcg plus MF59 adjuvant on Day 1 and Day 29
Drug: MF59 Adjuvant
Novartis supplies the MF59 adjuvant as an oil-in-water milky emulsion in single-use vials containing a fill volume of 0.7 mL. Group 1 through Group 5 will receive MF59 IM on Day 1.
Biological: A/H7N9 pIIV Vaccine
Sanofi supplies the monovalent influenza A/H7N9 virus vaccine as a sterile, clear, and slightly opalescent suspension in single-dose vials containing 15 mcg HA per 0.5 mL. Group 1 through Group5 will receive the IM vaccine on Day 1

Detailed Description:

The study will be conducted as a Phase I prospective, randomized study in healthy adult subjects at a single center. Adult subjects age 18 to 47 years and meeting all enrollment criteria will choose to participate as subjects who receive unadjuvanted or adjuvanted H7H9 pIIV vaccine followed by a live vaccine boost at 4 weeks (Group 1, n=24), 12 weeks (Group 2, n=24), or 24 weeks (Group 3, n=24), or to be in an observational group (Group 4, n=16) which will not be scheduled for a booster dose but will serve as a backup for dropouts in the other three groups. Within each group, subjects will be randomized at a 1:1 ratio to receive a single dose of either unadjuvanted H7N9 pIIV at 15 mcg (Subgroup A), or the same vaccine adjuvanted with the oil-in-water emulsion, MF59, (Subgroup B) delivered intramuscularly. Finally, a fifth group (Group 5, n=12) will receive two intramuscular doses of adjuvanted H7N9 pIIV separated by four weeks. The total duration of study participation for all subjects will be approximately 12 months.

  Eligibility

Ages Eligible for Study:   18 Years to 47 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Provide written informed consent prior to initiation of any study procedures, including future use of specimens.
  • Are able to understand and comply with planned study procedures and be available for all study visits.
  • Are males or non-pregnant, non-breastfeeding females, 18 to 47 years old, inclusive.
  • Are in good health, as determined medical history, and targeted physical examination to ensure any existing medical diagnoses or conditions (except those exclusionary) are stable.

Stable chronic medical condition - no change in prescription medication, dose, or frequency of medication in the last 3 months (defined as 90 days) and health outcomes of the specific disease are considered to be within acceptable limits in the last 6 months (defined as 180 days). Any change that is due to change of health care provider, insurance company etc., or that is done for financial reasons, as long as in the same class of medication, will not be considered a violation of this inclusion criterion. Any change in prescription medication due to improvement of a disease outcome, as determined by the site principal investigator or appropriate sub-investigator, will not be considered a violation of this inclusion criterion.

Subjects may be on chronic or as needed (prn) medications if, in the opinion of the site principal investigator or appropriate sub-investigator, they pose no additional risk to subject safety or assessment of reactogenicity and immunogenicity. Note: Topical, nasal, and inhaled medications (with the exception of steroids as outlined in the Subject Exclusion Criteria (see Section 5.2)), vitamins, and contraceptives are permitted.

  • Oral temperature is less than 100.4 degrees F
  • Pulse is 50 to 115 bpm, inclusive.
  • Systolic blood pressure is 85 to 150 mm Hg, inclusive.
  • Diastolic blood pressure is 55 to 95 mmHg, inclusive.
  • Women of childbearing potential in sexual relationships with men must use an acceptable method of conception from 30 days prior to pIIV administration until 90 days after pLAIV administration.Not sterilized via tubal ligation, bilateral oophorectomy or hysterectomy and still menstruating or < 1 year of the last menses if menopausal).Includes, but is not limited to, abstinence from intercourse with a male partner, monogamous relationship with a vasectomized partner, male condoms with the use of applied spermicide, intrauterine devices, and licensed hormonal methods, with use of a highly effective method of contraception for a minimum of 30 days prior to study product exposure and agree to practice highly effective contraception for the duration of study product exposure, including 2 months (defined as 60 days) after the last study vaccination. A highly effective method of contraception is defined as one which results in a low failure rate (i.e., less than 1 percent per year) when used consistently and correctly.
  • Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 24 hours prior to study vaccination.

Exclusion Criteria:

  • Have an acute illness within 72 hours prior to study vaccination.
  • Any medical disease or condition that, in the opinion of the investigator, is a contraindication to study participation.Includes medical disease or condition that would place the subject at an unacceptable risk of injury, render them unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or their successful completion of the study.
  • Have history of any significant acute or chronic medical conditions or need for chronic medications that, in the opinion of the investigator, will interfere with immunogenicity or affect safety.Chronic medical condition - a medical condition persisting 3 months (defined as 90 days) or longer
  • Have immunosuppression or are taking systemic immunosuppressants as a result of an underlying illness or treatment.
  • Diagnosis of asthma or reactive airway disease within the past 2 years.
  • History of surgical splenectomy.
  • Use of anticancer chemotherapy or radiation therapy (cytotoxic) within 36 months prior to vaccination.
  • Have known active neoplastic disease or a history of any hematologic malignancy.
  • Have known hepatitis B or hepatitis C infection.
  • Have known hypersensitivity or allergy to eggs, egg or chicken protein, squalene-based adjuvants, or other components of the study vaccine.
  • Known allergy or intolerance to oseltamivire.
  • Have a history of severe reactions following previous immunization with licensed or unlicensed influenza virus vaccines.
  • Have a history of Guillain-Barré Syndrome.
  • Have a history of neuralgia, paresthesia, neuritis, convulsions, or encephalomyelitis within 90 days prior to study vaccination.
  • Have a history of autoimmune disease.Including, but not limited to, neuroinflammatory diseases, vasculitis, clotting disorders, dermatitis, arthritis, thyroiditis, or muscle, liver, or kidney disease.
  • Have a history of alcohol or drug abuse within 5 years prior to study vaccination.
  • Have any diagnosis, current or past, of schizophrenia, bipolar disease, or other psychiatric diagnosis that may interfere with subject compliance or safety evaluations.
  • Have been hospitalized for psychiatric illness, history of suicide attempt, or confinement for danger to self or others within 10 years prior to study vaccination.
  • Have taken oral or parenteral corticosteroids of any dose within 30 days prior to study vaccination.
  • Chronic use (defined as daily use for > 7days within the 30 days prior to study vaccination) of any inhaled medication, including inhaled corticosteroids.
  • Received any licensed live vaccine within 30 days prior to pIIV vaccination. This is inclusive of licensed seasonal influenza vaccines.
  • Received any licensed inactivated vaccine within 14 days prior to pIIV vaccination. This is inclusive of licensed seasonal influenza vaccines.
  • Planned receipt of any vaccine from the first study vaccination through the follow-up visit at approximately 56 days after the second study vaccination. This is inclusive of licensed seasonal influenza vaccines
  • Received immunoglobulin or other blood products (with exception of Rho D immunoglobulin) within 90 days prior to study vaccination.
  • Received an experimental agent within 30 days prior to pIIV administration or planned receipt of an experimental agent to within 90 days after pLAIV administration.Includes vaccine, drug, biologic, device, blood product, or medication.-Plans to enroll in another clinical trial that could interfere with safety assessment of the investigational product at any time during the study period.Includes trials that have a study intervention such as a drug, biologic, or device
  • Prior participation in a clinical trial of influenza A/H7 vaccine or have a history of A/H7 actual or potential exposure or infection prior to the first study vaccination.Documented receipt of placebo in such a trial is not exclusionary
  • Plan to travel outside the U.S. (continental U.S., Hawaii and Alaska) in the time between the first study vaccination and 56 days after the second study vaccination.
  • Positive screening pregnancy test or other evidence of pregnancy.-Female subjects who are breastfeeding or plan to breastfeed at any given time from the first study vaccination until 30 days after their last study vaccination.
  • Seropositive to the H7N9 influenza A virus (serum HAI titer >1:8) during the screening period prior to the first study vaccination.
  • Positive urine drug screen for opiates and cocaine at the time of check-in for the period of confinement
  • Positive ELISA and confirmatory Western blot tests for human immunodeficiency virus-1 (HIV-1) during the screening period prior to LAIV vaccination.
  • Current smoker unwilling to stop smoking for the period of confinement. A nicotine patch during the period of confinement may be offered.
  Contacts and Locations
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: NCT02251288

Contacts
Contact: John Treanor (585) 275-5871 john_treanor@urmc.rochester.edu

Locations
United States, New York
University of Rochester Medical Center - Vaccine Research Unit Not yet recruiting
Rochester, New York, United States, 14642-0001
Sponsors and Collaborators
  More Information

No publications provided

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT02251288     History of Changes
Other Study ID Numbers: 13-0087, HHSN272201200005C
Study First Received: September 25, 2014
Last Updated: September 25, 2014
Health Authority: United States: Federal Government
United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
H7N9 pandemic, inactivated influenza vaccine (pIIV),MF59 adjuvant, live attenuated influenza vaccine (pLAIV)

Additional relevant MeSH terms:
Influenza, Human
Influenza in Birds
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
MF59 oil emulsion
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 30, 2014