Study of a Respiratory Syncytial Virus Candidate Encapsulated in a Lipid Nanoparticle Based Formulation in Adults Aged 18 to 50 Years and 60 Years and Older

• ClinicalTrials.gov Identifier: NCT05639894
• Recruitment Status: Active, not recruiting
• First Posted: December 7, 2022
• Last Update Posted: May 3, 2024
• Sponsor: Sanofi Pasteur, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Sanofi Pasteur, a Sanofi Company )

Tracking Information

• First Submitted Date: November 17, 2022
• First Posted Date: December 7, 2022
• Last Update Posted Date: May 3, 2024
• Actual Study Start Date: November 17, 2022
• Estimated Primary Completion Date: April 29, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 10, 2024)

• Presence of unsolicited systemic adverse events (AEs) [ Time Frame: Within 30 minutes after vaccination ]
  Number of participants experienciing unsolicited systemic adverse events
• Presence of solicited injection site or systemic reactions [ Time Frame: Within 7 days after vaccination ]
  Number of participants reporting:

  • injection site reactions: pain, erythema and swelling
  • systemic reactions: fever, headache, malaise, myalgia, arthralgia and chills
• Presence of unsolicited AEs [ Time Frame: Within 28 days after vaccination ]
  Number of participants experiencing unsolicited AEs
• Presence of medically attended adverse events (MAAEs) [ Time Frame: Within 28 days after vaccination ]
  Number of participants experiencing MAAEs
• Presence of serious adverse events (SAEs) [ Time Frame: Month 12 ]
  Number of participants experiencing SAEs
• Presence of adverse events of special interest (AESIs) [ Time Frame: Month 12 ]
  Number of participants experiencing AESIs
• Presence of out-of-range biological test results [ Time Frame: Within 7 days after vaccination ]
  Number of participants with biological safety assessment values out of normal range (as per the laboratory performing the test)
• Geometric Mean Titers (GMTs) of neutralizing antibody (nAb) titers pre-vaccination at Day 1 [ Time Frame: Day 1 ]
  Nab titers pre-vaccination
• Geometric Mean Titers (GMTs) of neutralizing antibody (nAb) titers post-primary vaccination at Day 29 [ Time Frame: Day 29 ]
  Nab titers post-vaccination

Original Primary Outcome Measures (submitted: December 2, 2022)

• Presence of immediate adverse events (AEs) [ Time Frame: Within 30 minutes after vaccination ]
  Number of participants experiencing immediate an immediate adverse event
• Presence of solicited injection site or systemic reactions [ Time Frame: Within 7 days after vaccination ]
  Number of participants reporting:

  • injection site reactions: pain, erythema and swelling
  • systemic reactions: fever, headache, malaise, myalgia, arthralgia and chills
• Presence of unsolicited AEs [ Time Frame: Within 28 days after vaccination ]
  Number of participants experiencing unsolicited AEs
• Presence of medically attended adverse events (MAAEs) [ Time Frame: Within 28 days after vaccination ]
  Number of participants experiencing MAAEs
• Presence of serious adverse events (SAEs) [ Time Frame: Month 12 ]
  Number of participants experiencing SAEs
• Presence of adverse events of special interest (AESIs) [ Time Frame: Month 12 ]
  Number of participants experiencing AESIs
• Presence of out-of-range biological test results [ Time Frame: Within 7 days after vaccination ]
  Number of participants with biological safety assessment values out of normal range (as per the laboratory performing the test)
• Geometric Mean Titers (GMTs) of neutralizing antibody (nAb) titers post-primary vaccination at Day 1 [ Time Frame: Day 1 ]
  Nab titers post-primary vaccination
• Geometric Mean Titers (GMTs) of neutralizing antibody (nAb) titers post-primary vaccination at Day 29 [ Time Frame: Day 29 ]
  Nab titers post-primary vaccination

Current Secondary Outcome Measures (submitted: April 10, 2024)

• Presence of immediate unsolicited systemic AEs (Stage 1) [ Time Frame: Within 30 minutes after vaccination ]
  Number of participants experiencing immediate unsolicitied systemic AEs
• Presence of solicited injection site or systemic reactions post-booster vaccination (Stage 1) [ Time Frame: Within 7 days after vaccination ]
  Number of participants reporting:

  • injection site reactions: pain, erythema and swelling
  • systemic reactions: fever, headache, malaise, myalgia, arthralgia and chills
• Presence of unsolicited AEs post-booster vaccination (Stage 1) [ Time Frame: Within 28 days after vaccination ]
  Number of participants experiencing unsolicited AEs
• Presence of MAAEs (Stage 1) [ Time Frame: Within 28 days after vaccination ]
  Number of participants experiencing MAAEs
• Presence of serious adverse events (SAEs) post-booster vaccination (Stage 1) [ Time Frame: Throughout the booster study, approximately 12 months ]
  Number of participants experiencing SAEs
• Presence of adverse events of special interest post-booster vaccination (Stage 1) [ Time Frame: Throughout the booster study, approximately 12 months ]
  Number of participants experiencing AESIs
• Presence of out-of-range biological test results post-booster vaccination (Stage 1) [ Time Frame: Within 7 days after vaccination ]
  Number of participants with biological safety assessment values out of normal range (as per the laboratory performing the test)
• RSV-A serum nAb titers at pre-vaccination (D01) and 28 days post- primary vaccination (D29) (Stage 1) [ Time Frame: Day 1, Day 29, Month 3, Month 6 and Month 12 ]
  RSV-A serum nAb titers at pre-vaccination (D01), 28 days (D29), and 3, 6, and 12 months post-primary vaccination
• GMTs of serum anti-F immunoglobulin G (IgG) antibody (Ab) titers post-primary vaccination (Stage 1) [ Time Frame: Day 1, Day 29, Month 3, Month 6 and Month 12 ]
  Serum anti-F IgG Ab titers at pre-vaccination (D01), 28 days (D29), and 3, 6, and 12 months post-primary vaccination
• GMTs of RSV-A serum nAb post-booster vaccination (Stage 1) [ Time Frame: Day 1, Day 29, Month 3, Month 6 and Month 12 post-booster ]
  RSV-A serum nAb titers at pre-booster vaccination, 28 days, and 3, 6, and 12 months post-booster vaccination
• GMTs of serum anti-F IgG Ab titers post-booster vaccination (Stage 1) [ Time Frame: Day 1, Day 29, Month 3, Month 6 and Month 12 post-booster ]
  Serum anti-F IgG Ab titers at pre-booster vaccination, 28 days, and 3, 6, and 12 months post- booster vaccination
• GMTs of serum anti-F IgG Ab titers pre-vaccination (Stage 2) [ Time Frame: Day 1 ]
  Nab titers pre-primary vaccination
• GMTs of serum anti-F IgG Ab titers post-vaccination (Stage 2) [ Time Frame: Day 29 ]
  Nab titers post-vaccination

Original Secondary Outcome Measures (submitted: December 2, 2022)

• Presence of immediate adverse events post-booster vaccination [ Time Frame: Within 30 minutes after vaccination ]
  Number of participants experiencing immediate an immediate adverse event
• Presence of solicited injection site or systemic reactions post-booster vaccination [ Time Frame: Within 7 days after vaccination ]
  Number of participants reporting:

  • injection site reactions: pain, erythema and swelling
  • systemic reactions: fever, headache, malaise, myalgia, arthralgia and chills
• Presence of unsolicited AEs post-booster vaccination [ Time Frame: Within 28 days after vaccination ]
  Number of participants experiencing unsolicited AEs
• Presence of medically attended adverse events post-booster vaccination [ Time Frame: Within 28 days after vaccination ]
  Number of participants experiencing MAAEs
• Presence of serious adverse events (SAEs) post-booster vaccination [ Time Frame: Throughout the booster study, approximately 12 months ]
  Number of participants experiencing SAEs
• Presence of adverse events of special interest post-booster vaccination [ Time Frame: Throughout the booster study, approximately 12 months ]
  Number of participants experiencing AESIs
• Presence of out-of-range biological test results post-booster vaccination [ Time Frame: Within 7 days after vaccination ]
  Number of participants with biological safety assessment values out of normal range (as per the laboratory performing the test)
• RSV-A serum nAb titers at pre-vaccination (D01) and 28 days post- primary vaccination (D29) [ Time Frame: Day 1, Day 29, Month 3, Month 6 and Month 12 ]
  RSV-A serum nAb titers at pre-vaccination (D01), 28 days (D29), and 3, 6, and 12 months post-primary vaccination
• GMTs of serum anti-F immunoglobulin G (IgG) antibody (Ab) titers post-primary vaccination [ Time Frame: Day 1, Day 29, Month 3, Month 6 and Month 12 ]
  Serum anti-F IgG Ab titers at pre-vaccination (D01), 28 days (D29), and 3, 6, and 12 months post-primary vaccination
• GMTs of RSV-A serum nAb post-booster vaccination [ Time Frame: Day 1, Day 29, Month 3, Month 6 and Month 12 post-booster ]
  RSV-A serum nAb titers at pre-booster vaccination, 28 days, and 3, 6, and 12 months post-booster vaccination
• GMTs of serum anti-F IgG Ab titers post-booster vaccination [ Time Frame: Day 1, Day 29, Month 3, Month 6 and Month 12 post-booster ]
  Serum anti-F IgG Ab titers at pre-booster vaccination, 28 days, and 3, 6, and 12 months post- booster vaccination

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of a Respiratory Syncytial Virus Candidate Encapsulated in a Lipid Nanoparticle Based Formulation in Adults Aged 18 to 50 Years and 60 Years and Older
• Official Title: A Phase I/IIa, Randomized, Placebo-controlled Multi-arm Dose-finding Study to Evaluate the Safety and Immunogenicity of a RSV Vaccine Candidate in Adult Participants 18 to 50 Years of Age in Phase I, and 60 Years and Older in Phase IIa

Brief Summary

Brief Summary of Stage 1:

The purpose Stage 1 (Phase I/IIa) is to assess the safety and immunogenicity of a single intramuscular (IM) injection of 3 dose-levels of an Respiratory Syncytial Virus (RSV) vaccine candidate formulated with 2 different lipid nanoparticles (LNPs) in healthy adult participants aged between 18 to 50 years, and 60 years and older. The primary objectives of this stage are to assess the safety and immunogenicity profiles across the dose-level groups (low, medium, and high doses) with 2 LNPs. This stage will evaluate the safety and immunogenicity of a booster vaccination administered 12 months after the primary vaccination in a subset of the study population.

Brief Summary of Stage 2:

The study also also incorporates a Stage 2 (Phase IIa, dose-ranging design) that includes adults aged 60 years and older to assess the safety and immunogenicity of different doses of RSV vaccine encapsulated in one of the LNPs. In the Phase IIa dose-ranging stage, eligible participants will be randomly assigned in a 1:1:1 ratio to receive a single IM administration of RSV vaccine candidate doses, or placebo. Multiple safety analyses will be performed, minimally at D07 and D28. Additional analyses may be performed as data are available.

Detailed Description

Stage 1:

The duration of each participant's participation is 12 months for the Sentinel and Main Cohorts, 24 months overall for the subset of participants enrolled in the Booster Cohort.

Treatment Duration:

• Sentinel Cohort: 1 intra-muscular (IM) injection. Participants will be followed for 12 months post-vaccination.
• Main Cohort: 1 IM injection. Participants will be followed for 12 months post-vaccination.
• Booster Cohort: 1 IM injection 12 months after the primary vaccination. Participants will be followed for 12 months after administration of the booster dose.

Stage 2:

The duration of each participant's participation is approximately 6 months.

Treatment Duration:

1 IM injection. Participants will be followed for approximately 6 months post vaccination

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Sequential (Phase I)/ parallel (Phase IIa)

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Sentinel Cohort: single-blind

• Investigators, study staff who conduct the safety assessment, and the participant will not know which study intervention is administered
• Sponsor study staff and study staff preparing/administering the study interventions and not involved with the safety evaluation will know which study intervention is administered Main and Booster Cohorts in Stage 1 and Stage 2: Modified double-blind
• Investigators, study staff who conduct the safety assessment, and the participant will not know which study intervention is administered
• Only the study staff who prepare and administer the study intervention and are not involved with the safety evaluation will know which study intervention is administered

Primary Purpose: Prevention

• Condition: Respiratory Syncytial Virus Immunization

Intervention

• Biological: RSV vaccine candiate formulation 1
  Pharmaceutical Form: Liquid frozen solution in a vial Route of Administration: Intramuscular injection
• Biological: RSV vaccine candidate formulation 2
  Pharmaceutical Form: Liquid frozen solution in a vial Route of Administration: Intramuscular injection
• Other: Placebo
  Pharmaceutical Form: Liquid Route of Administration: Intramuscular injection

Study Arms

• Experimental: Group 1: Sentinel and Main Cohorts (Stage 1)
  1 injection of RSV vaccine candidate (Dose A) via intramuscular injection
  Intervention: Biological: RSV vaccine candiate formulation 1
• Experimental: Group 2: Sentinel and Main Cohorts (Stage 1)
  1 injection of RSV vaccine candidate (Dose A) via intramuscular injection
  Intervention: Biological: RSV vaccine candidate formulation 2
• Experimental: Group 3: Sentinel and Main Cohorts (Stage 1)
  1 injection of RSV vaccine candidate (Dose B) via intramuscular injection
  Intervention: Biological: RSV vaccine candiate formulation 1
• Experimental: Group 4: Sentinel and Main Cohorts (Stage 1)
  1 injection of RSV vaccine candidate (Dose B) via intramuscular injection
  Intervention: Biological: RSV vaccine candidate formulation 2
• Experimental: Group 5: Sentinel and Main Cohorts (Stage 1)
  1 injection of RSV vaccine candidate (Dose C) via intramuscular injection
  Intervention: Biological: RSV vaccine candiate formulation 1
• Experimental: Group 6: Sentinel and Main Cohorts (Stage 1)
  1 injection of RSV vaccine candidate (Dose C) via intramuscular injection
  Intervention: Biological: RSV vaccine candidate formulation 2
• Placebo Comparator: Group 7: Main, Sentinel and Booster Cohorts (Stage 1)
  1 injection of placebo via intramuscular injection
  Intervention: Other: Placebo
• Experimental: Group 0: Phase IIa/Dose-ranging (Stage 2)
  1 injection of RSV vaccine candidate (Dose A) via intramuscular injection
  Intervention: Biological: RSV vaccine candiate formulation 1
• Experimental: Group 1: Phase IIa/Dose-ranging (Stage 2)
  1 injection of RSV vaccine candidate (Dose B) via intramuscular injection
  Intervention: Biological: RSV vaccine candidate formulation 2
• Placebo Comparator: Group 2: Phase 11a/Dose-ranging (Stage 2)
  1 injection of placebo via intramuscular injection
  Intervention: Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: May 2, 2024): 865
• Original Estimated Enrollment (submitted: December 2, 2022): 790
• Estimated Study Completion Date: April 29, 2025
• Estimated Primary Completion Date: April 29, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Sentinel Cohort Stage 1: Aged 18 to 50 years on the day of inclusion
• Main Cohort Stage 1 and Stage 2: Aged 60 years or older on the day of inclusion

Stage 1 and Stage 2:

• Sentinel Cohort: A female participant is eligible to participate if she is not pregnant or breastfeeding and:

  • 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.

• Main and Booster Cohorts: A female participant is eligible to participate if she is not pregnant or breastfeeding and:

  • 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.
• Able to attend all scheduled visits and to comply with all study procedures
• Informed consent form has been signed and dated

Exclusion Criteria:

• 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, 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
• History of RSV-associated illness, diagnosed clinically, serologically, or microbiologically in the last 12 months
• Previous history of myocarditis, pericarditis, and/or myopericarditis
• Thrombocytopenia or bleeding disorder, contraindicating IM injection based on investigator's judgment
• Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular injection
• 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 other than mRNA vaccine in the 4 weeks preceding any study intervention administration or planned receipt of any vaccine other than mRNA vaccine in the 4 weeks following any study intervention administration
• Receipt of any mRNA vaccine in the 60 days preceding any study intervention administration or planned receipt of any mRNA vaccine in the 60 days following any study intervention administration
• Previous vaccination against RSV with an investigational vaccine
• Receipt of immune globulins, blood, or blood-derived products in the past 3 months
• Receipt of oral or injectable antibiotic therapy within 72 hours prior to the first blood draw
• 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
• Self-reported or documented human immunodeficiency virus (HIV) detected by any FDA-approved/validated test, hepatitis B virus surface antigen (HBsAg), hepatits B core antibodies (HBcAb), or hepatitis C virus antibodies (HCV Abs), or positive SARS-CoV-2 RT-PCR or antigen test
• 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

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Puerto Rico, United States
• Removed Location Countries: Honduras, Mexico

Administrative Information

• NCT Number: NCT05639894
• Other Study ID Numbers: VAE00010; U1111-1271-1514 ( Registry Identifier: ICTRP ); 2023-505343-40 ( Registry Identifier: CTIS )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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

• Current Responsible Party: Sanofi ( Sanofi Pasteur, a Sanofi Company )
• Original Responsible Party: Sanofi
• Current Study Sponsor: Sanofi Pasteur, a Sanofi Company
• Original Study Sponsor: Sanofi
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

• PRS Account: Sanofi
• Verification Date: May 2024