H3N2 M2SR in Pediatric Population

NCT03553940 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 17-0012HHSN272201300021I
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase I double-blind, randomized, placebo-controlled study in 50 healthy adolescents and children, 9-17 years of age, inclusive, who are in good health and meet all eligibility criteria. This clinical trial is designed to assess the safety and immunogenicity of a prime-boost regimen of H3N2 M2SR intranasal influenza vaccine (manufactured by FluGen) followed by licensed inactivated Quadrivalent Influenza Vaccine (QIV) boost administered intramuscularly Subjects will be enrolled in one of two groups in a 1:1 ratio. Arm 1 will receive one dose of M2SR intranasally on Day 1 and one dose of QIV on Day 92. Arm 2 will receive one dose of placebo (saline) intranasally on Day 1, and one dose of QIV on Day 92. Study duration will be approximately 28 months with patient participation duration approximately 13 months. The primary study objective is to assess the safety and reactogenicity of a monovalent live attenuated influenza H3N2 M2SR vaccine.

Conditions

Influenza; Influenza Immunisation

Keywords

H3N2 M2SR Prime; Immunogenicity; Influenza; Pediatric Population; QIV; Safety; Vaccine

Outcome Measures

Primary Outcomes (5)

• Number of Participants With Adverse Events of Special Interest (AESIs)

  Adverse Events of Special Interest (AESIs) included medically significant wheezing and otitis media. AESIs were collected from receipt of the first study vaccination through 3 months after first vaccination.

  Day 1 through Day 92

• Number of Participants With New Onset Chronic Medical Conditions (NOCMCs)

  Participants were queried at each visit for the occurrence of new onset chronic medical conditions (NOCMCs). NOCMCs were collected from receipt of the first study vaccination through 3 months after first vaccination.

  Day 1 through Day 92

• Number of Participants With Serious Adverse Events (SAEs)

  SAEs included any untoward medical occurrence that resulted in death; was life threatening; was a persistent/significant disability/incapacity; required inpatient hospitalization or prolongation or a congenital anomaly/birth defect.

  Day 1 through Day 366

• Number of Participants With Solicited Reactogenicity

  Reactogenicity assessments included an assessment of solicited AEs occurring from the time of first study vaccination through 7 days after first vaccination. For upper respiratory symptoms, this included an assessment of runny nose, stuffy nose/ congestion, sneezing, nasal pain/irritation/nasal dryness, nasal bleeding/epistaxis, sinus pressure/pain, sore throat/sore/scratchy, itchy or painful throat, cough, and trouble breathing/shortness of breath. For general systemic symptoms, this included an assessment of reactions including fever, feverishness (chills/shivering/sweating), fatigue (tiredness), malaise, myalgia (body aches/muscular pain), arthralgia (joint pain), headache, flushing, decreased activity, decreased appetite, abdominal pain, nausea, vomiting, diarrhea, eye pruritus, eye redness (conjunctivitis), allergy, and wheezing.

  Day 1 through Day 8

• Number of Participants With Unsolicited Non-Serious Adverse Events

  Adverse events were defined as any untoward medical occurrence in a participant administered a pharmaceutical product regardless of its causal relationship to the study treatment. Non-serious AEs were collected from the time of first study vaccination through 21 days after first vaccination. Adverse events were MedDRA coded and are summarized by MedDRA System Organ Class (SOC).

  Day 1 through Day 22

Secondary Outcomes (53)

• Frequency of Conserved Internal Viral Protein-specific Spot Forming Cells

  Day 1 through Day 113

• Frequency of Influenza H3 HA-specific Spot Forming Cells for the H3N2 M2SR-like Virus A/Brisbane/10/2007

  Day 1 through Day 113

• Frequency of Influenza H3 HA-specific Spot Forming Cells for the H3N2 QIV-like Virus A/North Carolina/04/2016

  Day 1 through Day 113

• Frequency of Influenza H3 HA-specific Spot Forming Cells for the H3N2 QIV-like Virus A/Singapore/INFIMH-16-0019/2016

  Day 1 through Day 113

• Frequency of Influenza H3 HA-specific Spot Forming Cells for the H3N2 QIV-like Virus A/Kansas/14/2017

  Day 1 through Day 113

Study Arms (2)

Arm 1

EXPERIMENTAL

A single dose of monovalent live attenuated influenza H3N2 M2SR vaccine (M2SR) administered intranasally on Day 1, and a single dose of licensed quadrivalent influenza vaccine (QIV) administered intramuscularly on Day 92. N=25

Biological: Influenza Virus Monovalent A/H3N2/Bris 10 M2SR Live Vaccine; Biological: Quadrivalent MDCK Inactivated Influenza Vaccine

Arm 2

PLACEBO COMPARATOR

A single dose of Placebo administered intranasally on Day 1, and a single dose of licensed QIV administered intramuscularly on Day 92. N=25

Other: Placebo; Biological: Quadrivalent MDCK Inactivated Influenza Vaccine

Interventions

Influenza Virus Monovalent A/H3N2/Bris 10 M2SR Live Vaccine BIOLOGICAL

Live monovalent influenza A/H3N2-based M2SR (M2 defective Single Replication vaccine), comprised of 5 out of 8 gene segments on the donor virus influenza A/Puerto Rica/8/34. HA and NA derive from an A/Brisbane/10/2007-like virus. Administered intranasally as s single dose.

Arm 1

Placebo OTHER

H3N2 M2SR vaccine placebo (normal saline). Administered intranasally as a single dose.

Arm 2

Quadrivalent MDCK Inactivated Influenza Vaccine BIOLOGICAL

A quadrivalent cell culture inactivated vaccine (ccIV4) is an inactivated subunit influenza vaccine prepared from virus propagated in Madin Darby Canine Kidney (MDCK) cells indicated for the prevention of influenza disease caused by influenza virus subtypes A and type B contained in the vaccine. Administered intramuscularly as a single dose.

Arm 1; Arm 2

Eligibility Criteria

• Age: 9 Years - 17 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Parent(s)/legal guardian(s) must provide written informed consent prior to initiation of any study procedures, and subject must provide assent.
• Are able to understand and comply with planned study procedures and be available for all study visits.
• Are males or non-pregnant females, 9-17 years old, inclusive at the time of enrollment.
• Are in good health\*.
• Oral temperature is less than 100.0 degrees Fahrenheit.
• For female adolescent of child-bearing potential\* must agree to correctly use an acceptable method of contraception\*\* from 30 days prior to vaccination until 30 days after the last study vaccination.
• \*Defined by the onset of menses, and not sterilized via tubal ligation, bilateral oophorectomy, hysterectomy, or successful Essure(R) placement (permanent, non-surgical, non-hormonal sterilization) with documented radiological confirmation test at least 90 days after the procedure, and still menstruating.
• \*\*Includes non-male sexual relationships, abstinence from sexual intercourse with a male partner, monogamous relationship with a vasectomized partner, and correct use of male condoms with the use of applied spermicide, intrauterine devices, NuvaRing(R), and licensed hormonal methods such as implants, injectables, contraceptive patches or oral contraceptives ("the pill"). Method of contraception will be captured on the appropriate data collection form.
• Female adolescent of childbearing potential must have a negative urine pregnancy test within 24 hours prior to study vaccination.
• Males who are sexually active with a female of childbearing potential must agree not to father a child for 30 days after receipt of the first study vaccination.
• Agrees not to participate in another clinical trial during the study period.
• Agrees not to donate blood or blood products to a blood bank for 12 months after receiving the investigational vaccine.
• Weight = / \> 34 kg or 75 pounds.
• Hemoglobin = / \> 11.5 g/dL.
• Hematocrit \> 35%.

You may not qualify if:

• Have an acute illness\*, as determined by the site PI or appropriate sub-investigator, within 72 hours prior to each study vaccination.
• \*An acute illness which is nearly resolved with only minor residual symptoms remaining is allowable if, in the opinion of the site PI or appropriate sub-investigator, the residual symptoms will not interfere with the ability to assess safety parameters as required by the protocol.
• Have any medical disease or condition that, in the opinion of the site PI or appropriate sub-investigator, is a contraindication to study participation\*.
• \*Including acute or chronic medical disease or condition, defined as persisting for at least 90 days, that would place the subject at an unacceptable risk of injury, render the subject unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the subject's successful completion of this study.
• Have immunosuppression as a result of an underlying illness or treatment, or use of anticancer chemotherapy or radiation therapy (cytotoxic) within 3 years prior to study vaccination.
• Have known active neoplastic disease or a history of any hematologic malignancy. Non-melanoma skin cancers that are not active are permitted.
• Have known HIV, hepatitis B, or hepatitis C infection.
• Have a history of severe reactions following previous immunization with licensed or unlicensed influenza vaccines.
• History of anatomic disorder of the nares or nasopharynx (Deviated septum is allowed).
• History of chronic sinus infections.
• Have a history of Guillain-Barre Syndrome.
• Have a history of alcohol or drug abuse 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 prior to study vaccination.
• Have taken oral and/or nasal corticosteroids of any dose within 30 days prior to each study vaccination or plan to take in the 30 days following the first study vaccination.

Sponsors & Collaborators

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

Study Sites (1)

Saint Louis University - Center for Vaccine Development

St Louis, Missouri, 63104-1015, 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: Daniel F. Hoft, MD, PhD
• Organization: Saint Louis University

daniel.hoft@health.slu.edu

314-977-5500

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2018
• First Posted: June 12, 2018
• Study Start: August 15, 2018
• Primary Completion: August 27, 2020
• Study Completion: August 27, 2020
• Last Updated: October 21, 2021
• Results First Posted: October 21, 2021

Record last verified: 2021-03-01

Locations

US (1)