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Trial record 42 of 156 for:    Recruiting, Not yet recruiting, Available Studies | "Influenza, Human"

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

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ClinicalTrials.gov Identifier: NCT02251288
Recruitment Status : Recruiting
First Posted : September 29, 2014
Last Update Posted : September 15, 2017
Sponsor:
Information provided by (Responsible Party):

Study Description
Brief Summary:
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 may serve as a roll-over group for subjects who withdraw prior to the second vaccination but agree to remain in follow-up. A fifth group will receive two intramuscular doses of adjuvanted H7N9 pIIV separated by four weeks.

Condition or disease Intervention/treatment Phase
Avian Influenza Biological: Influenza Virus Vaccine, Live Attenuated H7N9 Anhui 2013/AA ca Biological: Influenza Virus Vaccine, Monovalent A/H7N9 A/Shanghai/2/2013 Drug: MF59 adjuvant Phase 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 may serve as a roll-over group for subjects who withdraw prior to the second vaccination but agree to remain in follow-up. 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 13 months. Recruitment, enrollment and administration of study product will be suspended when one of the following occurs in the clinical or research laboratory at the clinical site: at least two respiratory cultures or PCR assays are determined to be positive for influenza or at least 10% diagnostic tests (rapid tests, respiratory cultures or PCR assays) performed for influenza as positive during two consecutive weeks in the clinical or research laboratory at the clinical site. Recruitment, enrollment and administration of study product may be resumed after 2 weeks without a signal that influenza is still circulating in the community, as defined by the same measures that indicate the start of influenza season (i.e., less than 2 respiratory cultures or PCR assays are determined to positive for influenza or less than 10% of diagnostic tests performed or influenza with positive results).

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (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
Actual Study Start Date : July 14, 2015
Estimated Primary Completion Date : June 30, 2018
Estimated Study Completion Date : June 30, 2018

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
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 10^7 FFU H7 N9 pLAIV on Day 29
Biological: Influenza Virus Vaccine, Live Attenuated H7N9 Anhui 2013/AA ca
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.
Biological: Influenza Virus Vaccine, Monovalent A/H7N9 A/Shanghai/2/2013
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
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.
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 sprayer10^7 FFU H7 N9 pLAIV on Day 85
Biological: Influenza Virus Vaccine, Live Attenuated H7N9 Anhui 2013/AA ca
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.
Biological: Influenza Virus Vaccine, Monovalent A/H7N9 A/Shanghai/2/2013
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
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.
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 10^7 FFU H7 N9 pLAIV on Day 169
Biological: Influenza Virus Vaccine, Live Attenuated H7N9 Anhui 2013/AA ca
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.
Biological: Influenza Virus Vaccine, Monovalent A/H7N9 A/Shanghai/2/2013
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
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.
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
Biological: Influenza Virus Vaccine, Monovalent A/H7N9 A/Shanghai/2/2013
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
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.
Experimental: Group 5
12 patients receive A/H7N9 15 mcg plus MF59 adjuvant on Day 1 and Day 29
Biological: Influenza Virus Vaccine, Monovalent A/H7N9 A/Shanghai/2/2013
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
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.


Outcome Measures

Primary Outcome Measures :
  1. Geometric mean titers determined by neuraminidase inhibiting antibody by enzyme-linked lectin assay (ELLA) [ Time Frame: Approximately 28 days after each study vaccination ]
  2. Occurrence of solicited systemic and respiratory reactogenicity [ Time Frame: On the day of pLAIV vaccination through 10 days after pLAIV vaccination ]
  3. Occurrence of study vaccine-related serious adverse events [ Time Frame: Day 1 through approximately 6 months after pLAIV vaccination ]
  4. Occurrence of study vaccine-related unsolicited, non-serious adverse events [ Time Frame: Within 28 days of pLAIV vaccination ]
  5. Percentage of subjects achieving a serum HAI antibody titer of 1:40 or greater against the H7N9 antigen contained in the study vaccines [ Time Frame: Approximately 28 days after the second study vaccination ]
  6. 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 ]
  7. Percentage of subjects shedding vaccine virus as detected by rRT-PCR [ Time Frame: Within 7 days after pLAIV vaccination ]
  8. Percentage of subjects with mucosal immune responses by HA-specific ELISA performed on nasal wick. [ Time Frame: Day 1, through Day 365 ]
  9. Percentage of subjects with positive B cell responses by plasmablast assays on peripheral blood mononuclear cells [ Time Frame: Approximately 28 days after each study vaccination, and 56 and 180 days after the second study vaccination ]

Secondary Outcome Measures :
  1. Geometric mean titers of serum HAI and NtAb antibody [ Time Frame: Baseline and at approximately 28 days after each study vaccination and 56 and 180 days after the second vaccination. ]
  2. Occurrence of adverse events of special interest [ Time Frame: Day 29 through 12 months after the last pIIV vaccination ]
  3. Occurrence of local and systemic reactogenicity [ Time Frame: Day 29 through 7 days following vaccination ]
  4. Occurrence of new-onset chronic medical conditions [ Time Frame: Day 1 through 6 months after the last study vaccination ]
  5. Occurrence of study vaccine-related serious adverse events [ Time Frame: Day 1 to approximately 12 months after the last pIIV vaccination ]
  6. Occurrence of study vaccine-related unsolicited non-serious adverse events [ Time Frame: Within 28 days of pIIV vaccination ]
  7. Percentage of subjects achieving a serum HAI antibody titer of 1:40 or greater against the H7N9 antigen contained in the study vaccine [ Time Frame: Baseline and 28 days after the first study vaccination and 56 and 180 days after the second study vaccination ]
  8. Percentage of subjects achieving a serum NtAb titer of 1:40 or greater against the H7N9 antigen contained in the study vaccines [ Time Frame: Baseline and at approximately 28 days after each study vaccination and 56 and 180 days after the second vaccination ]
  9. 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 ]
  10. 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 ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 47 Years   (Adult)
Sexes Eligible for Study:   All
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. Note: 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 55 to 100 bpm, inclusive. -Systolic blood pressure is 90 to 140 mm Hg, inclusive. -Diastolic blood pressure is 55 to 90 mm Hg, inclusive. -Women of childbearing potential in sexual relationships with men must use an acceptable method of contraception from 30 days prior to pIIV administration until 90 days after last study vaccination. -Note: 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 3 months (defined as 90 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. -Note: 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. -Note: 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 oseltamivir. -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. -Note: 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. -Note: 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. -Note: Includes trials that have a study interven tion 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. -Note: 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 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02251288


Contacts
Contact: John Treanor 15852755871 john_treanor@urmc.rochester.edu

Locations
United States, New York
University of Rochester Medical Center - Vaccine Research Unit Recruiting
Rochester, New York, United States, 14642-0001
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
More Information

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT02251288     History of Changes
Other Study ID Numbers: 13-0087
HHSN272201200005C
First Posted: September 29, 2014    Key Record Dates
Last Update Posted: September 15, 2017
Last Verified: February 9, 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

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

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