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Assess the Safety and Immunogenicity of One or Two Doses of Sing2016 M2SR H3N2 Influenza 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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04960397
Recruitment Status : Recruiting
First Posted : July 13, 2021
Last Update Posted : March 25, 2022
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary:

This is a Phase 1b, randomized, double-blind, dose-escalating, age de-escalating, placebo-controlled study of a targeted 220 children, ages 6 months to 17 years, inclusive. This clinical trial is designed to assess the safety and immunogenicity of of one and two doses of Sing2016 M2SR H3N2 influenza vaccine (manufactured by FluGen) administered intranasally in seven cohorts of children. The first two groups to be vaccinated will be Cohorts 1 and 2.

Cohort 1 consists of 45 children 9-17 years old. Thirty of them will receive one dose of the vaccine at a dose of 10^9 TCID50, and 15 will receive one dose of placebo. Cohort 2 comprises 45 children 2-8 years old. Thirty of them will receive one dose of the vaccine at a dose of 10^8 TCID50 and 15 will receive one dose of placebo. Sites will enroll participants into Cohorts 1 and 2 simultaneously. Once 25 or more participants in each of the first 2 cohorts (Cohorts 1 and 2) have completed Day 8, SRC will evaluate if any halting rules are met and if it is deemed safe enrollment in Cohort 3 may open. Cohort 2 must fully enroll before enrollment in Cohort 3 may begin Cohort 3 consists of 25 children 2-8 years old. Fifteen of them will receive one dose of vaccine at 10^9 TCID50 and 10 will receive one dose of placebo. Once all 25 participants in Cohort 3 have completed Day 8 of follow-up, similar to Cohorts 1 and 2, the SRC will review to ensure no halting rules are met and if no rules are met, and the SRC determines it is safe to proceed, simultaneous enrollment into Cohorts 4 and 5 can begin. If any halting rules are met or Cohort 4 consists of 45 children 2-8 years old, thirty of them will receive two doses of vaccine at 10^9 TCID50 and 15 will receive two doses of placebo, with a 28-day interval between the first and second doses. Once 25 or more participants in Cohort 4 have completed Day 36 of follow-up, once again the SRC will review to ensure no halting rules are met. If progression is allowed, Cohort 5 will begin. Enrollment within the cohort will not halt during the SRC review of the lead-in group of eight children.

In Cohorts 5, 6, and 7, each will enroll 6- to 23-month-olds who are influenza-naïve (defined as children without receipt of influenza vaccine and without previous documented influenza infection). Cohort 5 consists of 8 children who will be randomized to receive two doses of 10^7 TCID50 Sing2016 M2SR (n=6) or two doses of placebo (n=2). A safety assessment will be conducted once all 8 have completed Day 8 to determine progression to Cohort 6. Cohort 6 will consist of 26 children. A lead-in group of 8 children will be randomly assigned to receive either two doses of 10^8 TCID50 of the Sing2016 M2SR (n=6) or two doses of placebo (n=2). Once the first 8 children have completed Day 8, the SRC will review the safety and determine if Cohort 7 may begin enrollment. The additional 18 children in Cohort 6 may continue to enroll during the SRC review. Overall, they will be assigned randomly to two doses of 10^8 TCID50 of the Sing2016 M2SR (n=12) or two doses of placebo (n=6). Cohort 7 will be the final cohort. Twenty-six children will be randomly allocated to receive two doses of either 10^9 TCID50 Sing2016 M2SR (n=18) or placebo (n=8). This cohort does not have a "lead-in" group since data from such a group are not needed to allow the enrollment in a subsequent cohort. However, the study-wide and individual halting rules still apply.

For all cohorts, a minimally acceptable pre-vaccination blood volume is set at one 5-mL tube of blood (Serum Separator Tube (SST) for serum), regardless of age. Should the site not be able to collect that blood before the first vaccination, the child will not be permitted to continue. After the administration of the above noted vaccine doses, safety will be assessed by the evaluation of reactogenicity from Days 1-8 for participants in Cohorts 1-3, who are receiving a single dose of vaccine or placebo, and from Days 1-8 and approximately Days 29-36 for participants in Cohorts 4, 5, 6, and 7, who are receiving 2 doses of vaccine or placebo. Study duration will be approximately 22 months with subject participation duration approximately three months. The primary study objective is to assess the safety and tolerability of one and two administrations of the Sing2016 M2SR H3N2 influenza vaccine at 10^7, 10^8, or 10^9 TCID50 delivered intranasally to healthy participants, 6 months to 17 years of age.


Condition or disease Intervention/treatment Phase
H3N2 Influenza Other: Placebo Biological: Sing2016 M2SR H3N2 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 220 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Phase 1b, Double-Blind, Randomized, Dose-Escalating, Age De-Escalating, Placebo-Controlled Study to Assess the Safety and Immunogenicity of One or Two Doses of Sing2016 M2SR H3N2 Influenza Vaccine Delivered Intranasally In a Healthy Pediatric Population 6 Months Through 17 Years of Age.
Actual Study Start Date : September 10, 2021
Estimated Primary Completion Date : November 1, 2023
Estimated Study Completion Date : November 1, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Flu Flu Shot Vaccines

Arm Intervention/treatment
Experimental: Cohort 1
A cohort of influenza non-naïve 25 healthy children, 9-17 years old, will receive a single dose of 10^9 TCID50 of intranasal Sing2016 M2SR H3N2 vaccine (N=30) or placebo (N=15) at Day 1. N=45.
Other: Placebo
Physiological saline, i.e., 0.9% sodium chloride.

Biological: Sing2016 M2SR H3N2
Novel intranasal live attenuated influenza vaccine with a defective M2 gene which renders the virus unable to replicate and generate progeny in animals and in humans, making its infectivity self-limiting. It induces both a mucosal and cell-mediated immune response and is administered intranasally. Supplied by Flugen Inc.

Experimental: Cohort 2
A cohort of influenza non-naïve 25 healthy children, 2-8 years old, will receive a single dose of 10^8 TCID50 of intranasal Sing2016 M2SR H3N2 vaccine (N=30) or placebo (N=15) at Day 1 intranasally. N= 45
Other: Placebo
Physiological saline, i.e., 0.9% sodium chloride.

Biological: Sing2016 M2SR H3N2
Novel intranasal live attenuated influenza vaccine with a defective M2 gene which renders the virus unable to replicate and generate progeny in animals and in humans, making its infectivity self-limiting. It induces both a mucosal and cell-mediated immune response and is administered intranasally. Supplied by Flugen Inc.

Experimental: Cohort 3
Once, there is sufficient evidence of safety and tolerability in Cohorts 1 and 2,and enrollment has completed of all 45 in each of these cohorts. Cohort 3 will begin enrollment. A cohort of influenza non-naïve 25 healthy children, 2-8 years old, will receive a single dose of 10^9 TCID50 of intranasal Sing2016 M2SR H3N2 vaccine (N=15) or placebo (N=10) at Day 1. N=25.
Other: Placebo
Physiological saline, i.e., 0.9% sodium chloride.

Biological: Sing2016 M2SR H3N2
Novel intranasal live attenuated influenza vaccine with a defective M2 gene which renders the virus unable to replicate and generate progeny in animals and in humans, making its infectivity self-limiting. It induces both a mucosal and cell-mediated immune response and is administered intranasally. Supplied by Flugen Inc.

Experimental: Cohort 4
Once, there is sufficient evidence of safety and tolerability in Cohort 3 and enrollment has been completed for this cohort, and fifth cohorts (Cohorts 4 and 5) will begin enrollment. A cohort of influenza non-naïve 25 healthy children, 2-8 years old, will receive two doses of the 10^9 TCID50 of intranasal Sing2016 M2SR H3N2 vaccine (N=30) or two doses of placebo (N=15) at Day 1 and Day 29. N=45.
Other: Placebo
Physiological saline, i.e., 0.9% sodium chloride.

Biological: Sing2016 M2SR H3N2
Novel intranasal live attenuated influenza vaccine with a defective M2 gene which renders the virus unable to replicate and generate progeny in animals and in humans, making its infectivity self-limiting. It induces both a mucosal and cell-mediated immune response and is administered intranasally. Supplied by Flugen Inc.

Experimental: Cohort 5
Participants in Cohort 4, will enroll concurrently. A cohort of influenza-naïve healthy children, 6-23 months old, will be randomized to receive two doses of 10^7 TCID50 of intranasal Sing2016 M2SR vaccine (N=6) or two doses of placebo (N=2) at Day 1 and Day 29. N=8.
Other: Placebo
Physiological saline, i.e., 0.9% sodium chloride.

Biological: Sing2016 M2SR H3N2
Novel intranasal live attenuated influenza vaccine with a defective M2 gene which renders the virus unable to replicate and generate progeny in animals and in humans, making its infectivity self-limiting. It induces both a mucosal and cell-mediated immune response and is administered intranasally. Supplied by Flugen Inc.

Experimental: Cohort 6
Once, there is sufficient evidence of safety in Cohort 5, Cohort 6 will begin enrollment. A cohort of influenza-naïve healthy children, 6-23 months old, where a lead-in group (N=20) will be randomly assigned to receive either two doses of 10^8 TCID50 of intranasal Sing2016 M2SR vaccine (N=6) or two doses of placebo (N=2) at Day 1 and Day 29. N=20. Once lead-in group completes Day 8, the SRC will review the safety and determine if Cohort 7 may begin enrollment. Additional group of children may continue to enroll during the SRC review, which will be assigned randomly to receive two doses of 10^8 TCID50 of intranasal Sing2016 M2SR (N=12) or two doses of placebo (N=6) at Day 1 and Day 29. N= 26
Other: Placebo
Physiological saline, i.e., 0.9% sodium chloride.

Biological: Sing2016 M2SR H3N2
Novel intranasal live attenuated influenza vaccine with a defective M2 gene which renders the virus unable to replicate and generate progeny in animals and in humans, making its infectivity self-limiting. It induces both a mucosal and cell-mediated immune response and is administered intranasally. Supplied by Flugen Inc.

Experimental: Cohort 7
Once, there is sufficient evidence of safety in Cohort 6, Cohort 7 will begin enrollment. A cohort of influenza-naïve healthy children, 6-23 months old, will be randomly assigned to receive two doses of 10^9 TCID50 dose of intranasal Sing2016 M2SR vaccine (N=18) or two doses of placebo (N=8) at Day 1 and Day 29. N=26
Other: Placebo
Physiological saline, i.e., 0.9% sodium chloride.

Biological: Sing2016 M2SR H3N2
Novel intranasal live attenuated influenza vaccine with a defective M2 gene which renders the virus unable to replicate and generate progeny in animals and in humans, making its infectivity self-limiting. It induces both a mucosal and cell-mediated immune response and is administered intranasally. Supplied by Flugen Inc.




Primary Outcome Measures :
  1. Occurrence of Adverse Events of Special Interest (AESIs) [ Time Frame: Day 1 through Day 395 ]
  2. Occurrence of New-onset Chronic Medical Conditions (NOCMCs) [ Time Frame: Day 1 through Day 395 ]
  3. Occurrence of Serious Adverse Event (SAEs) [ Time Frame: Day 1 through Day 395 ]
  4. Occurrence of solicited reactogenicity Adverse Events (AEs) [ Time Frame: Through 7 days post vaccination ]
    Both local and systemic solicited reactogenicity adverse events (AEs) will be assessed.

  5. Occurrence of unsolicited non serious Adverse Events (AE) [ Time Frame: Through 28 days post vaccination ]

Secondary Outcome Measures :
  1. Change from baseline in Geometric Mean Fold Rise (GMFR) in Hemagglutination inhibition (HAI) antibody titers [ Time Frame: Day 1 through Day 57 ]
    Hemagglutination inhibition (HAI) antibody titers against an H3N2 M2SR-like virus

  2. Change from baseline in Geometric Mean Fold Rise (GMFR) in neutralization titers [ Time Frame: Day 1 through Day 57 ]
    Neutralization titers against an H3N2 M2SR-like virus

  3. Change from baseline in Geometric mean titer (GMT) of secretory Immunoglobulin A (sIgA) [ Time Frame: Day 1 through Day 57 ]
    Secretory ImmunoglobulinA (sIgA) against an H3N2 M2SR-like virus

  4. Geometric mean fold rise (GMFR) of secretory Immunoglobulin A (sIgA) [ Time Frame: Day 1 through Day 57 ]
    Secretory ImmunoglobulinA (sIgA) against an H3N2 M2SR-like virus

  5. Geometric Mean Titers (GMTs) of serum Hemagglutination inhibition (HAI) antibody [ Time Frame: Up to Day 57 ]
    Hemagglutination inhibition (HAI) antibody against an H3N2 M2SR-like virus

  6. Geometric Mean Titers (GMTs) of serum neutralizing antibodies [ Time Frame: Up to Day 57 ]
    Serum neutralizing antibodies against an H3N2 M2SR-like virus

  7. Occurrence of greater than or equal to 2- and 4-fold mean rises in Hemagglutination inhibition (HAI) antibody titers [ Time Frame: Day 1 through Day 57 ]
    Hemagglutination inhibition (HAI) antibody titers against an H3N2 M2SR-like virus

  8. Occurrence of greater than or equal to 2- and 4-fold mean rises in neutralization titers [ Time Frame: Day 1 through Day 57 ]
    Neutralization titers against an H3N2 M2SR-like virus

  9. Occurrence of neutralization titer > / =1:40 [ Time Frame: Up to Day 57 ]
    Neutralization titer > / =1:40 against an H3N2 M2SR-like virus

  10. Occurrence of putative seroprotection [ Time Frame: Up to Day 57 ]
    Seroprotection defined as Hemagglutination inhibition (HAI) antibody titer > / = 1:40 against an H3N2 M2SR-like virus



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.


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Ages Eligible for Study:   6 Months to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

1. Participant is a male or female child aged 6 months to 17 years inclusive at time of enrollment (each cohort has its own age upper and lower limits*)

  • Cohort 1: 9-17 years (on or after the ninth birthday and before the eighteenth birthday at the time of the first dose); Cohorts 2, 3, and 4: 2-8 years (on or after the second birthday and before the ninth birthday at the time of the first dose); Cohorts 5, 6, and 7: 6 months to 23 months (on or after the sixth month of life based on calendar day and before the second birthday at the time of the first dose) 2. For Cohorts 1 to 4, receipt of at least 2 doses of seasonal influenza vaccine in the past.

    3. For Cohorts 5 to 7, receipt of no seasonal influenza vaccines in the past and no documented history of laboratory-confirmed influenza illness 4. Parent/guardian of the participating child provides written informed permission and participating child provides assent* prior to initiation of any study procedures

  • As appropriate by age or development and approved by the Institutional Review Board (IRB) 5. Parent/guardian and participant, as appropriate, are able to understand and comply with planned study procedures and are available for all study visits 6. Participant is in good health as assessed by the principal investigator or other designated study investigator*
  • Based on medical history and physical examination (physical examination may be done as part of routine medical care or specifically for eligibility screening) 7. Parent/guardian of the participating child agrees not to allow the participant to join another clinical trial that includes an investigational agent or device during the study period 8. A female participant of child-bearing potential* agrees to abstain from sexual intercourse or to correctly use an acceptable method of contraception**
  • A female of child-bearing potential is defined as a female who is post-menarchal and not sterilized via tubal ligation, bilateral oophorectomy, salpingectomy, hysterectomy, or successful Essure (R) placement (permanent, non-surgical, non-hormonal sterilization) with documented radiological confirmation test at least 90 days after the procedure. This applies only to participants in Cohort 1.

    **Acceptable methods of contraception must be used from 30 days prior to vaccination until 60 days after the last study vaccination (not Inactivated Influenza Vaccine (IIV4)) and include full abstinence from sexual intercourse with a male partner, monogamous relationship with vasectomized partner who has been vasectomized for 180 days or more or shown to be azoospermic prior to the participant receiving the study vaccination, barrier methods such as condoms or diaphragms/cervical cap, intrauterine devices, NuvaRing (R), and licensed hormonal methods such as implants, injectables, or oral contraceptives ("the pill").

    9. A female participant of child-bearing potential must have a negative urine pregnancy test within 24 hours prior to each study product 10. A male who is sexually active with a female of childbearing potential must agree to use an acceptable method of contraception*

  • From the time of the first dose of study vaccine until 60 days after receipt of the last dose study vaccine, only in cohort 1. The only acceptable method of contraception for males who are sexually active with females of childbearing potential is condoms.

Exclusion Criteria:

  1. Has a body temperature of 38 degrees Celsius or 100.4 degrees Fahrenheit (oral or axillary) or greater or another acute illness* within the 72 hours prior to study vaccination

    *Potential participants who are recovering from an acute illness and have residual minimal symptoms, which, in the opinion of the site principal investigator or appropriate sub-investigator, will not likely affect the evaluation of outcome measures are not ineligible. Temperature evaluation will not be performed as a study procedure on participants prior to administration of seasonal influenza vaccine

  2. Has any medical or mental health disease or condition* that would render study participation unsafe, or would interfere with the evaluation of the responses

    *In the opinion of the site principal investigator or appropriate sub-investigator

  3. Has had a wheezing episode or use of medications to treat asthma in the 12 months prior to screening.
  4. Has immunosuppression as a result of an underlying illness or treatment, a recent history or current use of immunosuppressive or immunomodulating disease therapy
  5. Has a diagnosis of or history of malignant neoplastic disease
  6. Has taken oral, parenteral (intramuscular or intravenous), inhaled, or nasal corticosteroids of any dose within 30 days prior to study vaccination
  7. Has known HIV, hepatitis B, or hepatitis C infection
  8. Has known hypersensitivity or allergy to any components of the study vaccine or material in the nasal delivery device*

    *Vaccine components: sucrose, sodium chloride, phosphate, glutamate; delivery device material: polycarbonate, polypropylene, synthetic rubber

  9. Has a history of severe reactions following previous immunization with licensed or unlicensed influenza vaccines?
  10. Has a history of an anatomic disorder of the nares or nasopharynx
  11. Has a history of chronic sinus infections
  12. Has a history of or currently smokes or vapes
  13. Has a history of Guillain-Barré syndrome
  14. Use of aspirin- or salicylate-containing products in the 30 days prior to or intends to use these products in the 30 days following administration of the investigational vaccine
  15. Has a history of documented influenza or receipt of influenza antiviral treatment in the 4 months prior to the first vaccination
  16. Receipt of any antiviral drug within the week prior to or following the investigational vaccine.
  17. Receipt of a licensed live vaccine within 30 days prior to the first study vaccination or plans to receive a licensed live vaccine within the 30 days after the last study vaccination.
  18. Receipt of licensed inactivated non-flu vaccine within 14 days prior to the first study vaccination, or plans to receive licensed, inactivated vaccine within the 30 days after the last study vaccination. ** Participants will be asked to avoid receipt of any routine licensed vaccines or vaccines under emergency use authorization during the periods described.
  19. Receipt of an influenza vaccine within the 4 months prior to the first study vaccination or plans to receive an influenza vaccine following the last study vaccination. Seasonal IIV4 will be received by participants as part of this trial.
  20. Receipt of immunoglobulin or other blood products within the 6 months prior to the first study vaccination or plans to receive during the period of study participation.
  21. Receipt of an experimental* agent or device within the 6 months prior to the first study vaccination or expects to receive an experimental agent or device during the study period.

    *Products for treatment or prevention of coronavirus disease 2019 (COVID-19), when received under Emergency Use Authorization (EUA) or full FDA approval and not as part of a clinical trial, will not be deemed "experimental" for the purposes of this criterion and will not make an otherwise eligible prospective participant ineligible.

  22. Is a family member of study personnel or personnel directly involved in the conduct or monitoring of the study.
  23. Receipt of an approved or experimental product for treatment or prevention of COVID-19 within the 10 days prior to study enrollment.

    • Participants may enroll if greater than 10 days after receipt of the COVID-19 treatment or prevention.
    • Participants who are receiving COVID-19 vaccines around the time of dosing of the investigational product will be asked to avoid COVID-19 vaccination within the 10 days before any vaccination in the study and within any reactogenicity period (the day of and 7 days following each intranasal vaccination).
  24. Inability of the study team to collect 5 mL of blood from the participant before the first vaccination (pre-vaccination blood).

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): NCT04960397


Contacts
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Contact: James D. Campbell 14107065328 jcampbel@som.umaryland.edu

Locations
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United States, Iowa
University of Iowa - Infectious Disease Clinic Recruiting
Iowa City, Iowa, United States, 52242-1009
United States, Maryland
University of Maryland School of Medicine - Center for Vaccine Development - Baltimore Recruiting
Baltimore, Maryland, United States, 21201-1509
United States, North Carolina
Duke Human Vaccine Institute - Duke Vaccine and Trials Unit Recruiting
Durham, North Carolina, United States, 27704
United States, Tennessee
Vanderbilt University - Pediatric - Vanderbilt Vaccine Research Center Recruiting
Nashville, Tennessee, United States, 37232-2573
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT04960397    
Other Study ID Numbers: 20-0009
75N93019C00055
First Posted: July 13, 2021    Key Record Dates
Last Update Posted: March 25, 2022
Last Verified: March 8, 2022

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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):
Healthy Pediatric Population
Immunogenicity
Influenza
M2SR H3N2 Influenza Vaccine
Phase 1b
Sing2016 M2SR H3N2 Influenza Vaccine
Additional relevant MeSH terms:
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Influenza, Human
Respiratory Tract Infections
Infections
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Diseases