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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05829356




Registration number
NCT05829356
Ethics application status
Date submitted
6/04/2023
Date registered
25/04/2023
Date last updated
9/05/2024

Titles & IDs
Public title
Substudy 01 - Safety and Immunogenicity of One Monovalent Modified mRNA Vaccine Encoding Influenza Hemagglutinin With LNP, in Adult Participants Aged 18 to 49 Years and 60 Years and Above
Scientific title
A Phase I, Parallel, Randomized, Active-controlled, Multi-center, Dose-escalation Study With Early Safety Data Reviews to Assess Safety and Immunogenicity of One Monovalent Modified Influenza mRNA Vaccine Encapsulated in LNP, in Adults Aged 18 to 49 Years and 60 Years and Above.
Secondary ID [1] 0 0
U1111-1278-3835
Secondary ID [2] 0 0
VAV00019
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Influenza Immunization 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - H3 mRNA / LNP Vaccine
Other interventions - Quadrivalent recombinant influenza Vaccine (RIV4)

Experimental: Group 1: H3 mRNA /LNP dose 1 - Participants will receive one intramuscular (IM) dose of H3 mRNA/LNP at Day 01

Experimental: Group 2: H3 mRNA /LNP dose 2 - Participants will receive one IM dose of H3 mRNA/LNP at Day 01

Experimental: Group 3: H3 mRNA /LNP dose 3 - Participants will receive one IM dose of H3 mRNA/LNP at Day 01

Experimental: Group 4: H3 mRNA /LNP dose 4 - Participants will receive one IM dose of H3 mRNA/LNP at Day 01

Experimental: Group 5: H3 mRNA /LNP dose 5 - Participants will receive one IM dose of H3 mRNA/LNP at Day 01

Active Comparator: Group 6 (Control Group): RIV4 dose - Participants will receive one IM dose of RIV4 at Day 01


Other interventions: H3 mRNA / LNP Vaccine
Pharmaceutical Form: Suspension for injection
Route of Administration: Intra-Muscular

Other interventions: Quadrivalent recombinant influenza Vaccine (RIV4)
Pharmaceutical Form: Solution for injection in a pre-filled syringe
Route of Administration: Intra-Muscular
Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants with immediate adverse events (AEs)
Timepoint [1] 0 0
Within 30 minutes after vaccination
Primary outcome [2] 0 0
Number of participants with solicited injection site or systemic reaction
Timepoint [2] 0 0
Within 7 days from vaccination
Primary outcome [3] 0 0
Number of participants with unsolicited adverse events
Timepoint [3] 0 0
Up to 28 days after injection
Primary outcome [4] 0 0
Presence of out-of-range biological test results
Timepoint [4] 0 0
At Day 3, Day 9 or Day 29
Primary outcome [5] 0 0
Presence of serious adverse events (SAEs)
Timepoint [5] 0 0
Throughout Study (up to approximately Month 6)
Primary outcome [6] 0 0
Presence of adverse events of special interest (AESIs)
Timepoint [6] 0 0
Throughout Study (up to approximately Month 6)
Primary outcome [7] 0 0
Hemagglutination inhibition (HAI) antibody (Ab) response to homologous strain
Timepoint [7] 0 0
Day 29
Primary outcome [8] 0 0
HAI titers at D01
Timepoint [8] 0 0
Day 1
Primary outcome [9] 0 0
HAI titers at D29
Timepoint [9] 0 0
Day 29
Primary outcome [10] 0 0
Individual HAI Ab titer ratio
Timepoint [10] 0 0
Day 1 through Day 29
Primary outcome [11] 0 0
Number of Participants with Vaccine Response or Seroconversion
Timepoint [11] 0 0
Day 1 through Day 29
Primary outcome [12] 0 0
2-fold and 4-fold rise in HAI titers from D01 to D29
Timepoint [12] 0 0
Day 1 to Day 29
Primary outcome [13] 0 0
Percentage of participants with detectable antibody HAI titers greater than or equal to (=) 40 [1/dil]
Timepoint [13] 0 0
Day 29
Primary outcome [14] 0 0
Geometric Mean Titers (GMTs) of neutralizing antibody (nAb) titers at Day 1
Timepoint [14] 0 0
Day 1
Primary outcome [15] 0 0
Geometric Mean Titers (GMTs) of neutralizing antibody (nAb) titers at Day 29
Timepoint [15] 0 0
Day 29
Primary outcome [16] 0 0
Individual nab titer ratio
Timepoint [16] 0 0
Day 1 through Day 29
Primary outcome [17] 0 0
2-fold and 4-fold increase in neutralizing Ab titers from D01 to D29
Timepoint [17] 0 0
Day 1 to Day 29

Eligibility
Key inclusion criteria
- Aged 18 years and above on the day of inclusion

*Aged 18 years to 49 years or 60 years and above on the day of inclusion (substudy 01)

- 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 postmenopausal for at least 1 year, or surgically sterile.

OR

• Is of childbearing potential and agrees to use an effective contraceptive method or
abstinence from at least 4 weeks prior to study intervention administration until at least
12 weeks after 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) at the screening
visit.

- Inclusion Criteria to be Checked at Visit 1 (Day 1)

Participants are eligible for the study only if all of the following criteria are met:

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 postmenopausal for at least 1 year, or surgically sterile.

OR

• Is of childbearing potential and agrees to use an effective contraceptive method or
abstinence from at least 4 weeks prior to study intervention administration until at least
12 weeks after 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 8 hours before the
first dose of study intervention.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- Previous vaccination against influenza in the previous 6 months with an
investigational or marketed vaccine

- Any screening laboratory parameter with laboratory abnormalities that are greater than
Grade 1 or deemed clinically significant in the opinion of the Investigator

- OR, any screening Liver Function Test (ALT, AST, Bilirubin) > 1.2x Upper Limit of
Normal or any other screening laboratory parameter outside of the range of normal
limits for age and gender

- Positive test for human immunodeficiency virus (HIV) antigen and/or antibodies (Abs),
hepatitis B (HB) virus surface antigen (HBsAg), hepatitis B core antibodies (HBcAb),
or hepatitis C virus antibodies (HCV Abs)

- 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 (eg,
polyethylene glycol [PEG], polysorbate); history of a life-threatening reaction to the
study interventions used in the study or to a product containing any of the same
substances; any allergic reaction (eg, anaphylaxis) after administration of mRNA
COVID-19 vaccine

- Previous history of myocarditis, pericarditis, and/or myopericarditis

- Screening electrocardiogram (ECG) or troponin value that is consistent with probable
or possible myocarditis, pericarditis, and/or myopericarditis or screening ECG that
demonstrates clinically relevant abnormalities that may affect participant safety or
study results

- Self-reported thrombocytopenia, contraindicating intramuscular vaccination based on
Investigator's judgment

- Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion,
contraindicating intramuscular vaccination based on Investigator's judgment

- Chronic illness that, in the opinion of the Investigator, is at a stage where it might
interfere with study conduct or completion

- 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 4 weeks preceding study enrollment or planned receipt of
any vaccine in the 4 weeks following study intervention administration

- Receipt of any mRNA vaccine/product in the 2 months preceding study enrollment or
planned receipt of any mRNA vaccine/product within the 2 months following study
intervention administration

- 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 study
enrollment or planned participation during the present study period in another
clinical study investigating a vaccine, drug, medical device, or medical procedure

- Previous vaccination against influenza in the previous 6 months with an
investigational or marketed vaccine

- Exclusion criteria to be checked at Visit 1 Day 1:

- Moderate or severe acute illness/infection (according to Investigator's judgment)
or febrile illness (temperature = 38.0°C [100.4°F]) on the day of vaccination. A
prospective participant should not be included in the study until the condition
has resolved or the febrile event has subsided.

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

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
12/04/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
14/03/2024
Sample size
Target
Accrual to date
Final
159
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
Investigational Site Number : 0360004 - Herston
Recruitment hospital [2] 0 0
Investigational Site Number : 0360001 - Morayfield
Recruitment hospital [3] 0 0
Investigational Site Number : 0360002 - Camberwell
Recruitment hospital [4] 0 0
Investigational Site Number : 0360003 - Adelaide
Recruitment postcode(s) [1] 0 0
4006 - Herston
Recruitment postcode(s) [2] 0 0
4506 - Morayfield
Recruitment postcode(s) [3] 0 0
3124 - Camberwell
Recruitment postcode(s) [4] 0 0
5000 - Adelaide
Recruitment outside Australia
Country [1] 0 0
United Kingdom
State/province [1] 0 0
Leicestershire
Country [2] 0 0
United Kingdom
State/province [2] 0 0
London, City Of
Country [3] 0 0
United Kingdom
State/province [3] 0 0
Sheffield

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Sanofi Pasteur, a Sanofi Company
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a Phase 1, parallel, randomized, active-controlled, multi-center, dose-esclation
study with a Master Protocol design which will include several substudies that are developed
to evaluate the safety and immunogenicity of different dose levels of modified messenger
ribonucleic acid (mRNA) vaccines encoding full length hemagglutinin (HA) sequence of
influenza virus encapsulated in lipid nanoparticles (LNPs) (hereafter referred to as HA mRNA
vaccines) compared to control(s). The HA mRNA vaccine candidates and control(s) are presented
in the substudy protocols.

The aim is to generate clinical data across different substudies to provide learnings
regarding the mRNA technology to support optimization of the mRNA platform including mRNA and
LNP design and to support the decision of LNP and dose selection for future projects using
mRNA technology.

The purpose of this Substudy 01 is to evaluate the safety and immunogenicity of a single IM
injection of up to 5 dose levels of a monovalent modified mRNA encoding the full-length HA
sequence of A/Tasmania/503/2020 (H3N2) influenza virus encapsulated in LNP (hereafter
referred to as H3 mRNA /LNP) administered as a single intramuscular (IM) injection in adults
18 to 49 years of age and 60 years of age and above, compared to the following active
control: a quadrivalent recombinant influenza vaccine (RIV4).
Trial website
https://clinicaltrials.gov/ct2/show/NCT05829356
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Sciences & Operations
Address 0 0
Sanofi Pasteur, a Sanofi Company
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries