Study on Two Adjuvanted Dose Levels of Panblok H7+MF59 Compared for Immunogenicity and Safety With an Unadjuvanted Dose of Panblok H7 in Participants 18 Years of Age and Older

A Parallel-group, Phase I/II, Randomized, Modified Double-blind, 3-arm, Active Comparator, Multi-center, Prevention Study to Evaluate the Immunogenicity and Safety of Two Adjuvanted Dose Levels of Panblok H7+MF59 Influenza Vaccine Compared With an Unadjuvanted Dose of Panblok H7 in Participants 18 Years of Age and Older

VAM00001 is a Phase I/II, randomized, modified double-blind, multi-center study.

The purpose of this study is to compare 2 dose levels of Panblok H7 (dose 1 and dose 2 of rHA) with a standard squalene dose of adjuvant MF59 to Panblok H7 (dose 3) unadjuvanted in approximately 700 adult participants in order to select one dose formulation to be used for further clinical development. The randomization ratio will be 3:3:1 for Panblok H7 (dose 1) + MF59, Panblok H7 (dose 2) + MF59, and Panblok H7 (dose 3) unadjuvanted, respectively. Each study group will be stratified into the age groups 18-64 years and ≥ 65 years of age.

The study duration for each participant will be approximately 13 months.

Study Overview

• Status: Completed
• Conditions: Influenza; Healthy Volunteers
• Intervention / Treatment: Biological: Panblok + MF59 Dose 1; Biological: Panblok + MF59 Dose 2; Biological: Unadjuvanted Panblok Dose 3

Detailed Description

The study duration for each participant will be approximately 13 months.

• Study Type: Interventional
• Enrollment (Actual): 581
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Trial Transparency email recommended (Toll free for US & Canada); Email: Contact-US@sanofi.com

Study Locations

• United States
  • Arizona
    • Mesa, Arizona, United States, 85206
      • Centricity Research-Mesa Site Number : 8400006
  • Florida
    • Hallandale Beach, Florida, United States, 33009
      • Velocity Clinical Research-Hallandale Beach Site Number : 8400026
    • Hollywood, Florida, United States, 33024
      • Research Centers of America Site Number : 8400024
    • Miami, Florida, United States, 33173
      • Suncoast Research Associates, LLC Site Number : 8400008
    • Saint Augustine, Florida, United States, 32086
      • St Johns Center for Clinical Research Site Number : 8400021
  • Georgia
    • Atlanta, Georgia, United States, 30331
      • CenExel ACMR (Atlanta Center for Medical Research) Site Number : 8400022
  • Indiana
    • Valparaiso, Indiana, United States, 46383
      • Velocity Clinical Research Valparaiso Site Number : 8400007
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Velocity Clinical Research Site Number : 8400027
  • North Carolina
    • Raleigh, North Carolina, United States, 27612
      • M3 Wake Research Inc Site Number : 8400010
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15236
      • Preferred Primary Care Physicians Site Number : 8400015
    • Pittsburgh, Pennsylvania, United States, 15243
      • Preferred Primary Care Physicians, Inc. Site Number : 8400002
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • Velocity Clinical Research Anderson Site Number : 8400016
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • WR-ClinSearch, LLC Site Number : 8400003
  • Texas
    • Austin, Texas, United States, 78759
      • Velocity Clinical Research Site Number : 8400019
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • JBR Clinical Research Site Number : 8400005
    • Salt Lake City, Utah, United States, 84121
      • Foothill Family Research-South Site Number : 8400009

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Aged 18 years or older on the day of inclusion
• Participants who are healthy as determined by medical evaluation including medical history and physical examination
• A female participant is eligible to participate if she is not pregnant or breastfeeding and one of the following conditions applies:

Is of non-childbearing potential. To be considered of non-childbearing potential, a female must be post-menopausal for at least 1 year, or surgically sterile.

OR Is of childbearing potential and agrees to use a highly effective contraceptive method or abstinence from at least 4 weeks prior to each study intervention administration until at least 12 weeks after the last study intervention administration.

• A female participant of childbearing potential must have a negative highly sensitive pregnancy test (urine or serum as required by local regulation) within 24 hours before the first dose of study intervention
• Informed consent form has been signed and dated

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

• Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)
• Known systemic hypersensitivity to any of the study intervention components, or history of a life-threatening reaction to the study interventions used in the study or to a product containing any of the same substances
• Thrombocytopenia or bleeding disorder contraindicating intramuscular injection based on investigator's judgement

• Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with study conduct or completion (1)

  (1) Chronic illness may include, but is not limited to, cardiac disorders, renal disorders, auto-immune disorders, diabetes, psychiatric disorders, or chronic infection

• Neoplastic disease or any hematologic malignancy (except localized skin or prostate cancer that is stable at the time of study intervention administration in the absence of therapy, and participants who have a history of neoplastic disease and who have been disease-free for ≥ 5 years)
• Moderate or severe acute illness/infection (according to investigator judgment) or febrile illness (temperature ≥ 100.4°F) on the day of study intervention administration. A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided
• Alcohol, prescription drug, or substance abuse that, in the opinion of the Investigator, might interfere with the study conduct or completion
• Receipt of any vaccine in the 14 days preceding Visit 1 or planned receipt of any vaccine prior to Visit 3, except for seasonal flu vaccine, which may be received at least 2 weeks after Visit 2
• Previous vaccination against H7N9 with an investigational vaccine
• Receipt of immune globulins, blood or blood-derived products in the past 3 months
• Participation at the time of study enrollment (or in the 4 weeks preceding the first study intervention administration) or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure
• Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily
• Identified as an Investigator or employee of the Investigator or study center with direct involvement in the proposed study, or identified as an immediate family member (ie, parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study
• Personal or family history of Guillain-Barré syndrome
• Self-reported seropositivity for Hepatitis B antigen or Hepatitis C

"The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial."

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; 2 doses, 21 days apart, of Panblok H7 dose 1 + MF59	Biological: Panblok + MF59 Dose 1; Pharmaceutical form: suspension for injection Route of administration: intramuscular
Experimental: Group 2; 2 doses, 21 days apart, of Panblok H7 dose 2 + MF59	Biological: Panblok + MF59 Dose 2; Pharmaceutical form: suspension for injection Route of administration: intramuscular
Active Comparator: Group 3; 2 doses, 21 days apart, of Panblok H7 dose 3 unadjuvanted	Biological: Unadjuvanted Panblok Dose 3; Pharmaceutical form: liquid for injection Route of administration: intramuscular

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Titers of Hemagglutination inhibition (HAI) Antibody (Ab) titers in participants	HAI Ab titers obtained on Day 22 for comparison with Day 01, Day 202 and Day 387 by HIH measurement method	At Day 22
Geometric Mean Titers of Hemagglutination inhibition (HAI) Antibody (Ab) titers in participants	HAI Ab titers obtained on Day 43 for comparison with Day 01, Day 202 and Day 387 by HIH measurement method	At Day 43
Geometric Mean of individual Ratio (GMR) of HAI Ab titers in participants	Individual HAI Ab titers ratio Day 22/Day 01 (baseline) by HIH measurement method	At Day 22
Geometric Mean of individual Ratio (GMR) of HAI Ab titers in participants	Individual HAI Ab titers ratio Day 43/Day 01 (baseline) by HIH measurement method	At Day 43
Geometric Mean of individual Ratio (GMR) of HAI Ab titers in participants	Individual HAI Ab titers ratio Day 202/Day 01 (baseline) by HIH measurement method	At Day 202
Geometric Mean of individual Ratio (GMR) of HAI Ab titers in participants	Individual HAI Ab titers ratio Day 387/ Day 01 (baseline) by HIH measurement method	At Day 387
Percentage of participants with seroconversion	Seroconversion: defined as titer < 10 (1/dilution [1/dil]) on Day 01 and post-vaccination titer ≥ 40 (1/dil) on Day 22 or Day 43; or titer ≥ 10 (1/dil) on Day 01 and a ≥ 4-fold increase in titer (1/dil) on Day 22 or Day 43 Vaccination taking place on Day 01 and Day 22 by HIH measurement method	At 21 days after each vaccination
Percentage of participants with HAI titer above predefined threshold	Participants with HAI Ab titers ≥ 40 (1/dil) by HIH measurement method	At Day 01
Percentage of participants with HAI titer above predefined threshold	Participants with HAI Ab titers ≥ 40 (1/dil) by HIH measurement method	At Day 22
Percentage of participants with HAI titer above predefined threshold	Participants with HAI Ab titers ≥ 40 (1/dil) by HIH measurement method	At Day 43
Percentage of participants with HAI titer above predefined threshold	Participants with HAI Ab titers ≥ 40 (1/dil) by HIH measurement method	At Day 202
Percentage of participants with HAI titer above predefined threshold	Participants with HAI Ab titers ≥ 40 (1/dil) by HIH measurement method	At Day 387
Percentage of participants with detectable HAI Ab titer	Detectable HAI Ab titer, ie, with a titer ≥ 10 (1/dil) by HIH measurement method	At Day 01
Percentage of participants with detectable HAI Ab titer	Detectable HAI Ab titer, ie, with a titer ≥ 10 (1/dil) by HIH measurement method	At Day 22
Percentage of participants with detectable HAI Ab titer	Detectable HAI Ab titer, ie, with a titer ≥ 10 (1/dil) by HIH measurement method	At Day 43
Percentage of participants with detectable HAI Ab titer	Detectable HAI Ab titer, ie, with a titer ≥ 10 (1/dil) by HIH measurement method	At Day 202
Percentage of participants with detectable HAI Ab titer	Detectable HAI Ab titer, ie, with a titer ≥ 10 (1/dil) by HIH measurement method	At Day 387
Geometric Mean Titers Ratio (GMTR) for Group1/Group3, Group2/Group3, and Group2/Group1	Ratio of GMTs for Group1/Group3, Group2/Group3, and Group2/Group1 Vaccination taking place on Day 01 and Day 22 by HIH measurement method	At 21 days after each vaccination
Geometric Mean Titers of Neutralization (NT) Ab titer in participants	Neutralization (NT) Ab titer obtained on Day 22 for comparison with D01, D202, and D387 by SN measurement method	At Day 22
Geometric Mean Titers of Neutralization (NT) Ab titer in participants	Neutralization (NT) Ab titer obtained on Day 43 for comparison with D01, D202, and D387 by SN measurement method	At Day 43
Geometric Mean of individual Ratio (GMR) of NT Ab titers in participants	Individual NT Ab titer ratio Day 22/Day 01 (baseline) by SN measurement method	At Day 22
Geometric Mean of individual Ratio (GMR) of NT Ab titers in participants	Individual NT Ab titer ratio Day 43/Day 01 (baseline) by SN measurement method	At Day 43
Geometric Mean of individual Ratio (GMR) of NT Ab titers in participants	Individual NT Ab titer ratio Day 202/Day 01 (baseline) by SN measurement method	At Day 202
Geometric Mean of individual Ratio (GMR) of NT Ab titers in participants	Individual NT Ab titer ratio Day 387/Day 01 (baseline) by SN measurement method	At Day 387
Percentage of participants with NT Ab titer above predefined threshold	Participants with NT Ab titers ≥ 20 (1/dil), ≥ 40 (1/dil), ≥ 80 (1/dil) on Day 22; compared to Day 01, Day 202, and Day 387 by SN measurement method	At Day 22
Percentage of participants with NT Ab titer above predefined threshold	Participants with NT Ab titers ≥ 20 (1/dil), ≥ 40 (1/dil), ≥ 80 (1/dil) on Day 43; compared to Day 01, Day 202, and Day 387 by SN measurement method	At Day 43
Percentage of participants with fold-increase in NT Ab titer	Fold-increase in NT Ab titer [post/pre] ≥ 2 and ≥ 4 on Day 22 and Day 43, as compared to D01 Vaccination taking place on Day 01 and Day 22 by SN measurement method	At 21 days after each vaccination
Percentage of participants with detectable NT Ab titer	Detectable NT Ab titer, ie, with a titer ≥ 10 (1/dil) by SN measurement method	At Day 01
Percentage of participants with detectable NT Ab titer	Detectable NT Ab titer, ie, with a titer ≥ 10 (1/dil) by SN measurement method	At Day 22
Percentage of participants with detectable NT Ab titer	Detectable NT Ab titer, ie, with a titer ≥ 10 (1/dil) by SN measurement method	At Day 43
Percentage of participants with detectable NT Ab titer	Detectable NT Ab titer, ie, with a titer ≥ 10 (1/dil) by SN measurement method	At Day 202
Percentage of participants with detectable NT Ab titer	Detectable NT Ab titer, ie, with a titer ≥ 10 (1/dil) by SN measurement method	At Day 387
GMR for Group1/Group3, Group2/Group3, and Group2/Group1	Ratio of GMs for Group1/Group3, Group2/Group3, and Group2/Group1 Vaccination taking place on Day 01 and Day 22 by SN measurement method	At 21 days after each vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with immediate adverse events (AEs)	Immediate adverse events are any unsolicited systemic adverse events	Within 30 minutes after each vaccination
Number of participants with solicited injection site and systemic reactions	Solicited injection site reactions include injection site pain, erythema, swelling, induration, ecchymosis Solicited systemic reactions include fever, headache, malaise, myalgia	Up to 7 days after each/any vaccination
Number of participants with unsolicited AEs	Unsolicited (spontaneously reported) AEs, not fulfilling criteria for solicited adverse reactions	Up to 21 days after each/any vaccination
Number of participants with medically adverse events (MAAEs)	MAAEs	From Day 01 up to Day 387
Number of participants with adverse events of special interest (AESIs)	AESIs	From Day 01 up to Day 387
Number of participants with serious adverse events (SAEs) (including AESIs)	SAEs (including AESIs)	From Day 01 up to Day 387

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company
• Investigators: Study Director: Clinical Sciences & Operations, MCM Vaccines B.V.

Study record dates

Study Major Dates

• Study Start (Actual): November 3, 2022
• Primary Completion (Actual): February 18, 2023
• Study Completion (Actual): February 13, 2024

Study Registration Dates

• First Submitted: October 20, 2022
• First Submitted That Met QC Criteria: November 4, 2022
• First Posted (Actual): November 7, 2022

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 7, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Physiological Effects of Drugs; Immunologic Factors; Adjuvants, Immunologic; MF59 oil emulsion
• Other Study ID Numbers: VAM00001; U1111-1256-9115 (Registry Identifier: ICTRP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No