Assess the Safety and Immunogenicity of One or Two Doses of Sing2016 M2SR H3N2 Influenza Vaccine

NCT04960397 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: 20-000975N93019C00055
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 4

Brief Summary

This is a Phase 1b, randomized, double-blind, dose-escalating, age de-escalating, placebo-controlled study of 200 children, ages 6 months to 17 years. This clinical trial is designed to assess the safety, tolerability/reactogenicity, and immunogenicity of one and two doses of Sing2016 M2SR H3N2 influenza vaccine (manufactured by FluGen) administered intranasally in seven cohorts of children. The study design includes pre-planned Safety Review Committee( SRC) reviews. 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. Cohort 3 consists of 25 children 2-8 years old. 15 of them will receive one dose of vaccine at 10\^9 TCID50 and 10 will receive one dose of placebo. Once 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 any concerns are raised by the SRC, an external SMC may meet to discuss the data for recommendations on either progression or clinical trial modification before progression to the next cohort. Cohort 4 consists of 25 children 2-8 years old; 15 of them will receive two doses of vaccine at 10\^9 TCID50 and 10 will receive two doses of placebo, with a 28-day interval between the first and second doses. Due to the limited availability of product, and funding to support additional years of enrollment into Cohorts 5, 6, and 7, the decision was made to stop enrollment after the final participant was enrolled into Cohort 4. 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\^8 or 10\^9 TCID50 delivered intranasally to healthy participants, 2 to 17 years of age.

Conditions

H3N2 Influenza

Keywords

Healthy Pediatric Population; Immunogenicity; Influenza; M2SR H3N2 Influenza Vaccine; Phase 1b; Sing2016 M2SR H3N2 Influenza Vaccine

Outcome Measures

Primary Outcomes (7)

• Number and Percentage of Participants Experiencing a Solicited Reactogenicity Adverse Event

  Number and percentage of participants in Cohorts 1-4 each and across Cohorts 1-4 who experience systemic (solicited or local) reactogenicity events, of all severity grades and by grade

  Day of first vaccination through 7 days post-dose 1

• Number and Percentage of Participants Experiencing a Solicited Reactogenicity Adverse Event

  Number and percentage of participants in Cohort 4 who experience systemic (solicited or local) reactogenicity events, of all severity grades and by grade

  Day of second vaccination through 7 days post-dose 2 (Day 29 to Day 36)

• Number and Percentage of Participants Experiencing an Unsolicited Non-serious Adverse Event (AE)

  Number and percentage of participants in Cohorts 1-4 each and across Cohorts 1-4 who experience unsolicited non-serious adverse events, of all severity grades and by grade

  Day of first vaccination through 28 days post-dose 1

• Number and Percentage of Participants Experiencing an Unsolicited Non-serious Adverse Event (AE)

  Number and percentage of participants in Cohort 4 who experience unsolicited non-serious adverse events, of all severity grades and by grade

  Day of second vaccination through 7 days post-dose 2 (Day 29 to Day 36)

• Number and Percentage of Participants Experiencing an Adverse Event of Special Interest (AESI)

  Number and percentage of participants in Cohorts 1-4 each and across Cohorts 1-4 who experience AESIs

  Day 1 through final visit in the month of April of the calendar year following enrollment (up to 14 months post-baseline)

• Number and Percentage of Participants Experiencing a Serious Adverse Event (SAE)

  Number and percentage of participants in Cohorts 1-4 each and across Cohorts 1-4 who experience serious adverse events (SAEs)

  Day 1 through final visit in the month of April of the calendar year following enrollment (up to 14 months post-baseline)

• Number and Percentage of Participants Experiencing a New-onset Chronic Medical Condition (NOCMC)

  Number and percentage of participants in Cohorts 1-4 each and across Cohorts 1-4 who experience new-onset chronic medical conditions (NOCMCs)

  Day 1 through final visit in the month of April of the calendar year following enrollment (up to 14 months post-baseline)

Secondary Outcomes (10)

• Number and Percentage of Participants With Putative Seroprotection Against an H3N2 M2SR-like Virus

  Day 1, Day 29 (Cohorts 1, 2, and 3), and Day 57 (Cohort 4)

• Number and Percentage of Participants With Serum Neutralizing Antibody Titer Against an H3N2 M2SR-like Virus Greater Than or Equal to 1:40

  Day 1, Day 29 (Cohorts 1, 2, and 3), and Day 57 (Cohort 4)

• Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Antibodies Against an H3N2 M2SR-like Virus

  Day 1, Day 29 (Cohorts 1, 2, and 3), and Day 57 (Cohort 4)

• Geometric Mean Titers (GMTs) of Serum Neutralizing Antibodies Against an H3N2 M2SR-like Virus

  Day 1, Day 29 (Cohorts 1, 2, and 3), and Day 57 (Cohort 4)

• Geometric Mean Fold Rise (GMFR) in Serum Hemagglutination Inhibition (HAI) Antibody Titers Against an H3N2 M2SR-like Virus

  Day 29 (Cohorts 1, 2, and 3) and Day 57 (Cohort 4)

Study Arms (4)

Cohort 1

EXPERIMENTAL

A cohort of influenza non-naïve 45 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; Biological: Sing2016 M2SR H3N2

Cohort 2

EXPERIMENTAL

A cohort of influenza non-naïve 45 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; Biological: Sing2016 M2SR H3N2

Cohort 3

EXPERIMENTAL

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; Biological: Sing2016 M2SR H3N2

Cohort 4

EXPERIMENTAL

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=15) or two doses of placebo (N=10) at Day 1 and Day 29. N=25

Other: Placebo; Biological: Sing2016 M2SR H3N2

Interventions

Placebo OTHER

Physiological saline, i.e., 0.9% sodium chloride.

Cohort 1; Cohort 2; Cohort 3; Cohort 4

Sing2016 M2SR H3N2 BIOLOGICAL

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.

Cohort 1; Cohort 2; Cohort 3; Cohort 4

Eligibility Criteria

• Age: 6 Months - 17 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• \. 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.
• \. 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").
• \. 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.

You may not qualify if:

• 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
• 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
• Has a history of provider-diagnosed asthma requiring the use of medications at any age or has had a wheezing episode or use of medications to treat asthma in the 12 months prior to screening.
• Has immunosuppression as a result of an underlying illness or treatment, a recent history or current use of immunosuppressive or immunomodulating disease therapy
• Has a diagnosis of or history of malignant neoplastic disease
• Has taken oral, parenteral (intramuscular or intravenous), inhaled, or nasal corticosteroids of any dose within 30 days prior to study vaccination
• Has known HIV, hepatitis B, or hepatitis C infection
• 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
• Has a history of severe reactions following previous immunization with licensed or unlicensed influenza vaccines
• Has a history of an anatomic disorder of the nares or nasopharynx
• Has a history of chronic sinus infections
• Has a history of or currently smokes or vapes

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (4)

University of Iowa - Infectious Disease Clinic

Iowa City, Iowa, 52242, United States

Location

University of Maryland, School of Medicine, Center for Vaccine Development and Global Health

Baltimore, Maryland, 21201-1509, United States

Location

Duke Vaccine and Trials Unit

Durham, North Carolina, 27704, United States

Location

Vanderbilt University - Pediatric - Vanderbilt Vaccine Research Center

Nashville, Tennessee, 37232-2573, United States

Location

Related Publications (1)

• Taaffe J, Ostrowsky JT, Mott J, Goldin S, Friede M, Gsell P, Chadwick C. Advancing influenza vaccines: A review of next-generation candidates and their potential for global health impact. Vaccine. 2024 Dec 2;42(26):126408. doi: 10.1016/j.vaccine.2024.126408. Epub 2024 Oct 5.

  PMID: 39369576 DERIVED

MeSH Terms

Conditions

Influenza, Human

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Dr. James D. Campbell
• Organization: University of Maryland

jcampbel@som.umaryland.edu

410-706-5328

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants, site investigators, and study personnel performing any study-related assessments following study product administration are blinded to product received. Laboratory personnel performing immunological assays will receive serum blinded to participant ID number, specimen visit number, and allocation group.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2021
• First Posted: July 13, 2021
• Study Start: September 10, 2021
• Primary Completion: April 12, 2024
• Study Completion: April 12, 2024
• Last Updated: August 3, 2025
• Results First Posted: June 6, 2025

Record last verified: 2025-04-18

Locations

US (4)