ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 3 of 26 for:    influenza and universal

Safety and Immunogenicity of a Live-attenuated Universal Flu Vaccine Followed by an Inactivated Universal Flu Vaccine

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03300050
Recruitment Status : Active, not recruiting
First Posted : October 3, 2017
Last Update Posted : December 8, 2017
Sponsor:
Collaborators:
Icahn School of Medicine at Mount Sinai
Children's Hospital Medical Center, Cincinnati
Duke University
The EMMES Corporation
GlaxoSmithKline
Information provided by (Responsible Party):
PATH

Brief Summary:
The clinical study will evaluate safety and the immune response of a prime- boost regimen with a live attenuated influenza vaccine (LAIV) prime and an inactivated split influenza vaccine (IIV) boost with or without adjuvant.

Condition or disease Intervention/treatment Phase
Influenza Vaccine Biological: cH8/1N1 LAIV Biological: cH5/1N1 IIV + adjuvant Biological: cH5/1N1 IIV Biological: cH8/1N1 IIV + adjuvant Biological: Normal saline Biological: Phosphate buffered saline Phase 1

Detailed Description:
This is a prospective, multi-center, randomized, controlled, observer-blind, Phase 1 trial in healthy male and female adults 18 through 39 years of age to evaluate safety and the immune response of a prime boost regimen with LAIV prime and IIV boost with or without adjuvant . Up to 65 eligible subjects will participate and will be randomized 4:3:1:3:2 to one of five groups to receive a first dose of study cH8/1N1 LAIV (or placebo) or study cH8/1N1 IIV + AS03A adjuvant (or placebo) followed three months later by study cH5/1N1 IIV +/- AS03A adjuvant (or placebo).

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 65 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Eligible enrolled subjects will be randomized to any of the treatment arms (LAIV-IIV, Groups 1, 2, and 3; or IIV-IIV, Groups 4 and 5) under one allocation sequence, stratified by site, to allow comparability between study groups, such as LAIV-IIV vs IIV-IIV regimens (Groups 1 vs 4). Groups 1-3 will be inpatient and receive either LAIV or placebo as nasal drops at Dose 1. Groups 4-5 ill be outpatient and receive either IIV or placebo as an injection at Dose 1.
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: An unblinded pharmacist will prepare Dose 1 and Dose 2. Participants and study staff will remain blinded to their exact treatment group but will be unblinded to their overall group allocation (inpatient or outpatient).
Primary Purpose: Prevention
Official Title: A Phase 1, Randomized, Controlled, Observer-blind Study to Assess the Reactogenicity, Safety, and Immunogenicity of a Live Attenuated Universal Influenza Vaccine (cH8/1N1 LAIV) Administered as a Single Priming Dose Followed Three Months Later by a Single Booster Dose of an Inactivated Universal Influenza Vaccine (cH5/1N1 IIV) (Adjuvanted With AS03A or Unadjuvanted) in 18 Through 39 Year-old Healthy Subjects, Contrasted With a Two Dose Schedule of an Inactivated Universal Influenza Vaccine (cH8/1N1 IIV + AS03A Followed Three Months Later by cH5/1N1 IIV + AS03A)
Actual Study Start Date : October 10, 2017
Estimated Primary Completion Date : April 13, 2018
Estimated Study Completion Date : March 5, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Flu Flu Shot
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + adjuvant
Participants will receive 0.5mL cH8/1N1 LAIV administered as 0.25mL per nostril on D1 followed by 0.5mL cH5/1N1 IIV + AS03A administered as an injection on D85.
Biological: cH8/1N1 LAIV
One 0.5 mL dose contains cH8/1N1 LAIV titer of 10^7.5 +/- 0.5, egg infective dose 50%
Biological: cH5/1N1 IIV + adjuvant
One 0.5 mL dose contains 15μg split hemagglutinin (HA) with AS03 adjuvant
Other Name: cH5/1N1 IIV + AS03 adjuvant
Experimental: Group 2: cH8/1N1 LAIV and cH5/1N1 IIV
Participants will receive 0.5mL cH8/1N1 LAIV administered as 0.25mL per nostril on D1 followed by 0.5mL cH5/1N1 IIV administered as an injection on D85.
Biological: cH8/1N1 LAIV
One 0.5 mL dose contains cH8/1N1 LAIV titer of 10^7.5 +/- 0.5, egg infective dose 50%
Biological: cH5/1N1 IIV
One 0.5 mL dose contains 15μg split hemagglutinin (HA)
Placebo Comparator: Group 3: Placebo
Participants will receive 0.5mL of normal saline administered as 0.25mL per nostril on D1 followed by 0.5mL phosphate buffered saline administered as an injection on D85.
Biological: Normal saline
Administered as 0.25 mL nasal drops
Biological: Phosphate buffered saline
Administered as 0.5 mL injection
Experimental: Group 4: cH8/1N1 IIV + adjuvant and cH5/1N1 IIV + adjuvant
Participants will receive 0.5mL of cH8/1N1 IIV + AS03A administered as an injection on D1 followed by 0.5mL cH5/1N1 IIV + AS03A administered as an injection on D85.
Biological: cH5/1N1 IIV + adjuvant
One 0.5 mL dose contains 15μg split hemagglutinin (HA) with AS03 adjuvant
Other Name: cH5/1N1 IIV + AS03 adjuvant
Biological: cH8/1N1 IIV + adjuvant
One 0.5 mL dose contains 15μg split hemagglutinin (HA) with AS03 adjuvant
Other Name: cH8/1N1 IIV + AS03 adjuvant
Placebo Comparator: Group 5: Placebo
Participants will receive 0.5mL phosphate buffered saline administered as an injection on D1 followed by 0.5mL phosphate buffered saline administered as an injection on D85.
Biological: Phosphate buffered saline
Administered as 0.5 mL injection



Primary Outcome Measures :
  1. Occurrence of solicited local and general adverse events (AEs) post-vaccination [ Time Frame: 7 days post each dose ]
    Frequency of solicited local and general AEs post-vaccination

  2. Occurrence unsolicited AEs post-vaccination [ Time Frame: 28 days post each dose ]
    Frequency of unsolicited AEs post-vaccination

  3. Occurrence of hematological and biochemical laboratory abnormalities post-vaccination [ Time Frame: Days 8, 29, 85, 92, and 113 ]
    Frequency of hematological and biochemical laboratory abnormalities post-vaccination.

  4. Occurrence of medically attended events (MAEs), laboratory confirmed influenza like-illnesses (LC-ILI), potential immune-mediated disease (pMIDs), and serious adverse events (SAEs) [ Time Frame: through day 113 ]
    Frequency of MAEs, LC-ILI, pMIDs, and SAEs



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 39 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Able to understand planned study procedures and demonstrate comprehension of the protocol procedures and knowledge of study by passing a written examination prior to vaccination.
  • In the opinion of the investigator, can and will comply with the requirements of the protocol (e.g., completion of the diary cards, return for follow-up visits).
  • Written informed consent obtained from the subject prior to performance of any study specific procedure.
  • Male or non-pregnant female between, and including, 18 and 39 years of age at the time of the first vaccination.
  • Healthy subjects without acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality*.
  • Female subjects of non-childbearing potential may be enrolled in the study.
  • Female subjects of childbearing potential must have a negative pregnancy test within 24 hours of vaccination.
  • Female subjects of childbearing potential must have practiced adequate contraception for 30 days prior to first vaccination and agree to continue adequate contraception until 2 months after completion of the vaccination series (Month 5).
  • Male subjects must be surgically sterile (e.g., vasectomy) or agree to practice adequate contraception from the first vaccination until 2 months after completion of the vaccination series (Month 5). Please refer to the glossary of terms for the definition of adequate contraception.

Exclusion Criteria:

  • Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines.
  • Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe.
  • Medically diagnosed deviated nasal septum or nasal obstruction.
  • Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs within 6 months before the first dose.
  • Administration of long-acting immune-modifying drugs (e.g., infliximab, rituximab) within 6 months before the first dose (Visit 03), or planned administration any time during the study period.
  • Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the first dose (Visit 03) up to Month 15 (Visit 15)
  • Persons who should be annually vaccinated against influenza who live with or care for persons at high risk for influenza-related complications.
  • History of influenza vaccination within 6 months prior to study enrollment or unwillingness to forego seasonal influenza vaccination during the entire study period.
  • History of vaccination with an investigational pandemic influenza vaccine other than an H1N1pdm09 vaccine.
  • Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
  • Infection with human immunodeficiency virus regardless of clinical stage of immunodeficiency.
  • History of current infection with hepatitis B virus or hepatitis C virus regardless of clinical presentation.
  • History of or current autoimmune disease.
  • Subjects diagnosed with excessive daytime sleepiness or narcolepsy; or history of narcolepsy in a subject's parent or sibling.
  • History of Guillain-Barré syndrome.
  • History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines (including egg proteins); a history of anaphylactic-type reaction to consumption of eggs; or a history of severe adverse reaction to a previous influenza vaccine.
  • Hypersensitivity to latex.
  • Administration of immunoglobulins and/or any blood products during the period starting 3 months before the first dose of study vaccines or planned administration during the study period.
  • Pregnant or lactating female.
  • Female planning to become pregnant or male planning to father a child or either planning to discontinue contraceptive precautions.
  • Current smoker.
  • During screening, have a positive test for opiates without a prescription.
  • History of chronic alcohol consumption and/or drug abuse as deemed by the investigator to render the potential subject unable/unlikely to provide accurate safety reports.
  • Have a history of convulsions or encephalomyelitis within 90 days 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.
  • Blood donation or planned blood donation within 30 days prior to the study vaccination through 30 days after the last blood drawn for this study.
  • Have signs or symptoms that could confound or confuse assessment of study vaccine reactogenicity.
  • Any hematological or biochemical parameter that is out of range of normal, and is considered clinically significant by the investigator.

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): NCT03300050


Locations
United States, North Carolina
Duke University
Durham, North Carolina, United States, 27710
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
Sponsors and Collaborators
PATH
Icahn School of Medicine at Mount Sinai
Children's Hospital Medical Center, Cincinnati
Duke University
The EMMES Corporation
GlaxoSmithKline
Investigators
Principal Investigator: David Bernstein, MD Children's Hospital Medical Center, Cincinnati
Principal Investigator: Jeffrey Guptill, MD Duke University

Responsible Party: PATH
ClinicalTrials.gov Identifier: NCT03300050     History of Changes
Other Study ID Numbers: CVIA 057 (1082166-1)
First Posted: October 3, 2017    Key Record Dates
Last Update Posted: December 8, 2017
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by PATH:
live attenuated influenza vaccine
inactivated influenza vaccine

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Vaccines
Immunologic Factors
Physiological Effects of Drugs