H3N2 M2SR in Pediatric Population

NCT ID: NCT03553940

Last Updated: 2021-10-21

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

43 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-08-15

Study Completion Date

2020-08-27

Brief Summary

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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.

Detailed Description

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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. The secondary study objectives are to identify circulating and mucosal antibody responses induced by H3N2 M2SR vaccination and to identify cellular immune responses induced by H3N2 M2SR vaccination.

Conditions

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Influenza Influenza Immunisation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Arm 1

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

Group Type EXPERIMENTAL

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

Intervention Type 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.

Quadrivalent MDCK Inactivated Influenza Vaccine

Intervention Type 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 2

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

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

Quadrivalent MDCK Inactivated Influenza Vaccine

Intervention Type 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.

Interventions

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

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.

Intervention Type BIOLOGICAL

Placebo

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

Intervention Type OTHER

Quadrivalent MDCK Inactivated Influenza Vaccine

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.

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

1. Parent(s)/legal guardian(s) must provide written informed consent prior to initiation of any study procedures, and subject must provide assent.
2. Are able to understand and comply with planned study procedures and be available for all study visits.
3. Are males or non-pregnant females, 9-17 years old, inclusive at the time of enrollment.
4. Are in good health\*.

\*As determined by medical history and physical examination to evaluate acute or currently ongoing chronic medical diagnoses or conditions, defined as those that have been present for at least 90 days, which would affect the assessment of the safety of subjects or the immunogenicity of study vaccinations. Chronic medical diagnoses or conditions should be stable for the last 60 days (no hospitalizations, ER, or urgent care for condition and no adverse symptoms that need medical intervention). This includes no change in chronic prescription medication, dose, or frequency as a result of deterioration of the chronic medical diagnosis or condition in the 60 days prior to enrollment. Any prescription 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 deviation 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 deviation 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 and do not indicate a worsening of medical diagnosis or condition. Similarly, medication changes subsequent to enrollment and study vaccination are acceptable provided there was no deterioration in the subject's chronic medical condition that necessitated a medication change, and there is no additional risk to the subject or interference with the evaluation of responses to study vaccination. Note: Low dose topical steroids, herbals, vitamins, and supplements are permitted.
5. Oral temperature is less than 100.0 degrees Fahrenheit.
6. 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.
7. Female adolescent of childbearing potential must have a negative urine pregnancy test within 24 hours prior to study vaccination.
8. 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.
9. Agrees not to participate in another clinical trial during the study period.
10. Agrees not to donate blood or blood products to a blood bank for 12 months after receiving the investigational vaccine.
11. Weight = / \> 34 kg or 75 pounds.
12. Hemoglobin = / \> 11.5 g/dL.
13. Hematocrit \> 35%.
14. Ferritin level = / \> 15 ng/mL.
15. Parent/legal guardian must provide consent to future use of stored samples.

Exclusion Criteria

1. 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.
2. 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.
3. 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.
4. Have known active neoplastic disease or a history of any hematologic malignancy. Non-melanoma skin cancers that are not active are permitted.
5. Have known HIV, hepatitis B, or hepatitis C infection.
6. Have a history of severe reactions following previous immunization with licensed or unlicensed influenza vaccines.
7. History of anatomic disorder of the nares or nasopharynx (Deviated septum is allowed).
8. History of chronic sinus infections.
9. Have a history of Guillain-Barre Syndrome.
10. Have a history of alcohol or drug abuse prior to study vaccination.
11. Have any diagnosis, current or past, of schizophrenia, bipolar disease, or other psychiatric diagnosis that may interfere with subject compliance or safety evaluations.
12. Have been hospitalized for psychiatric illness, history of suicide attempt, or confinement for danger to self or others prior to study vaccination.
13. 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.
14. Have taken high-dose\*,\*\* inhaled corticosteroids within 30 days (prior to study vaccination).

\*High-dose defined as per age as using inhaled high dose per reference chart.

\*\*https://www.nhlbi.nih.gov/files/docs/guidelines/asthma\_org.pdf.
15. Use of aspirin or salicylate-containing products 30 days prior to the first vaccination.
16. Recurring or active wheezing or diagnosis of asthma, or history of significant wheezing\*.

\*Medically significant wheezing: defined as wheezing on physical exam plus sign of respiratory distress (tachypnea, retractions, or dyspnea), hypoxemia (O2 saturation \< 95%), or new bronchodilator prescription, or use of daily bronchodilator therapy (not on an "as needed" basis).
17. Received any licensed live or inactivated vaccine within 30 days prior to or plan to receive any licensed live or inactivated vaccine within 30 days after each study vaccination.
18. Received any influenza vaccine (inactivated or live) within 6 months prior to the first study vaccination and until the end of the study.
19. Received immunoglobulin or other blood products within 6 months prior to study vaccination.
20. Received an experimental agent\* within 30 days prior to the first study vaccination, or expects to receive an experimental agent\*\* during the 12-month trial-reporting period.

\*Including vaccine, drug, biologic, device, blood product, or medication.

\*\*Other than from participation in this study.
21. Are participating or plan to participate in another clinical trial with an interventional agent\* that will be received during the 12-month trial-reporting period.

\*Including agent (licensed or unlicensed vaccine, drug, biologic, device, blood product, or medication) during the 12-month study period.
22. Prior history of H3N2 actual or potential exposure or infection prior to the first study vaccination, or receipt of experimental vaccines within the past year prior to the first study vaccine.
23. Female adolescent subject who is breastfeeding or plans to breastfeed at any given time from the first study vaccination until 30 days after the last study vaccination.
24. Blood donation within 30 days prior to the study vaccination through 30 days after the last blood drawn for this study.
25. Have signs or symptoms that could confound or confuse assessment of study vaccine reactogenicity\*.

\*The study vaccination should be postponed/deferred until signs or symptoms have resolved and if within the acceptable protocol-specified window for that visit.
26. Have received any antiviral drug within 3 days of study vaccination.
Minimum Eligible Age

9 Years

Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Saint Louis University - Center for Vaccine Development

St Louis, Missouri, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 39369576 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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HHSN272201300021I

Identifier Type: -

Identifier Source: secondary_id

17-0012

Identifier Type: -

Identifier Source: org_study_id