Healthy Volunteers
Conditions
Keywords
Human Metapneumovirus, Respiratory Syncytial Virus, Vaccine
Brief summary
The main purposes of this study are to assess the safety, reactogenicity and immunogenicity of 4 dose levels of the bivalent combination Respiratory Syncytial Virus (RSV) / human Metapneumovirus (hMPV) vaccine candidate VXB-241 when administered as a single-dose regimen to healthy adults 60 to 83 years of age, and to assess the impact of revaccination approximately 1 year later.
Detailed description
This is a multi-center study in older adults with run-in in younger adults to evaluate the safety, reactogenicity, and immunogenicity of 4 dose levels of VXB-241. The total planned sample size is 136 randomized participants, composed of 16 younger adults 18 to 40 years of age and 120 older adults 60 to 83 years of age who are in good health, which allows for many chronic conditions, if well controlled and compatible with self-sufficiency in self-care and daily living activities. Recruitment will be in 2 stages: * Stage 1 (Sequential Cohort Stage, N=32). Four cohorts (Cohorts 1 to 4), each of 8 participants, will be enrolled sequentially. In each cohort, 4 younger adults will be enrolled first, followed by 4 older adults. Younger and older adult participants will be randomized with 3:1 ratio to VXB-241 at increasing dose (60 microgram (mcg), 120 mcg, 240 mcg, 480 mcg in Cohorts 1 to 4, respectively) or Placebo. A Safety Monitoring Committee will make recommendations on escalation from one cohort to the next and from Stage 1 to Stage 2 based on safety and reactogenicity data collected over 1 week after investigational medicinal product (IMP) dosing. * Stage 2 (Concurrent Group Stage, N=104). Older adult participants will be randomized concurrently with unequal randomization to 1 of 6 treatment groups: VXB-241 60 mcg (Group 1a), VXB-241 120 mcg (1b), VXB-241 240 mcg (1c), VXB-241 480 mcg (1d), commercial RSV vaccine Arexvy (2a), Placebo (3a). The planned total sample size of each treatment group, combining Stage 1 and Stage 2, is N=20. The overall planned duration of the study is approximately 6 months for younger adult participants and approximately 2 years for older adult participants. At the end of the 1st year, older adult participants will receive a second IMP injection (revaccination): participants who received VXB-241 (at any dose) will be assigned 1:1 to revaccination with VXB-241 (Group 1e) or Placebo (1f); participants who received Arexvy will be revaccinated with placebo (2b); participants who received Placebo will be revaccinated with VXB-241 (3b). The dose of VXB-241 for revaccination will be 240 mcg (RSV preF 120 mcg + HMPV preF 120 mcg) (based on 1 month post 1st IMP injection results).
Interventions
BIOLOGICALVXB-241 120 mcg (Medium Dose)
VXB-241 medium dose, single, IM injection.
BIOLOGICALVXB-241 240 mcg (Medium-high Dose)
VXB-241 medium-high dose, single, IM injection.
BIOLOGICALVXB-241 480 mcg (High Dose)
VXB-241 high dose, single, IM injection.
BIOLOGICALVXB-241 240 mcg
VXB-241 240 mcg (RSV preF 120 mcg + hMPV preF 120 mcg) (based on 1 month post 1st IMP injection results) single, IM injection.
OTHERPlacebo
Placebo, single, IM injection.
BIOLOGICALArexvy 120 mcg
Arexvy 120 mcg, single, IM injection.
BIOLOGICALVXB-241 60 mcg (Low Dose)
VXB-241 low dose, single, IM injection.
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Outcomes Assessor)
Intervention model description
Stage 1 is a sequential assignment followed by Stage 2 parallel assignment.
Eligibility
Sex/Gender
ALL
Age
18 Years to 83 Years
Healthy volunteers
Yes
Inclusion criteria
1. Male or female, 18 to 40 years of age (yoa) (younger adult) or 60 to 83 yoa (older adult). 2. Evidence of signed and dated participant informed consent form (PICF) prior to any study procedure, indicating that the participant has been informed of all pertinent aspects of the study. 3. Willingness and ability to comply with the planned study visits and calls, procedures, and restrictions for the duration of the study. 4. Good health, which allows for pre-existing well-controlled and low impact chronic diseases, except for the diseases listed in the
Exclusion criteria
. A disease is defined as well-controlled and low impact if it did not require meaningful change in therapy or unplanned medical visits in the previous 3 months and allows participant's primary responsibility for self-care and daily living activities. 5. Non-smoker or occasional smoker, defined as smoking less than 10 nicotine-containing cigarettes/ vapes/cigars/pipe fills per week. 6. Contraception: heterosexually active participants of childbearing potential able and willing to use a double contraceptive method for at least 4 weeks before and 12 weeks after the first IMP injection at Visit 2 (all participants of childbearing potential) and second IMP injection at Visit 6 (male older adults of childbearing potential). 7. Body Mass Index (BMI) \>=17.0 kilogram per square meter (kg/m\^2) and less than or equal to (\<=) 35.0 kg/m\^2.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Older Adult Participants With 1 or More Unsolicited AEs | 1 month after first IMP injection (Days 1 to 30) | — |
| Proportion of Older Adult Participants With 1 or More Solicited AEs | 7 days after first IMP injection (Days 1 to 8) | — |
| Geometric Mean Fold Increase (GMFI) of RSV-A, RSV-B, hMPV-A, and hMPV-B Serum Neutralizing Antibody Titers in Older Adults | Pre-injection baseline to 1 month (Day 30) after first IMP injection | GMFI is defined as geometric mean of ratios of specific antibody titer/concentration at each post-vaccination time point over pre-vaccination baseline. |
| Ratio of Dose-response Curves for GMFIs of RSV-A, RSV-B, hMPV-A and hMPV-B Serum Neutralizing Antibody Titers in Older Adults | Pre-injection baseline to 1 month (Day 30) after first IMP injection | Ratio of VXB-241 dose versus GMFI of RSV-A, RSV-B, hMPV-A and hMPV-B will be calculated. |
Secondary
| Measure | Time frame |
|---|---|
| Proportion of Older Adult Participants With 1 or More Unsolicited AEs and With 1 or More Severe Unsolicited AE | 1 month after first IMP injection (Days 1 to 30) and 1 month after second IMP injection (revaccination, Days 364 to 394) |
| Proportion of Older Adult Participants With Serious Adverse Events (SAEs), AEs of Special Interest (AESIs), and Premature Discontinuation Associated AEs (PDAEs) | 1 month after first IMP injection (Days 1 to 30) and 1 month after second IMP injection (revaccination, Days 364 to394), and throughout follow-up (Days 1 to 720) |
| Mean Change From Baseline for Abnormal and Severe Abnormal Hematology Laboratory Values for Hemoglobin in Older Adults | 7 days (Day 8) and 1 month (Day 30) after first IMP injection, and 1 month (Day 394) after second IMP injection (revaccination |
| Mean Change From Baseline for Abnormal and Severe Abnormal Hematology Laboratory Values for Red Blood Cells, White Blood Cells, and Platelet Count in Older Adults | 7 days (Day 8) and 1 month (Day 30) after first IMP injection, and 1 month (Day 394) after second IMP injection (revaccination |
| Mean Change From Baseline for Abnormal and Severe Abnormal Blood Chemistry Laboratory Values for Alanine Transaminase (ALT), Aspartate Transaminase (AST), and Alkaline Phosphatase in Older Adults | 7 days (Day 8) and 1 month (Day 30) after first IMP injection, and 1 month (Day 394) after second IMP injection (revaccination |
| Mean Change From Baseline for Abnormal and Severe Abnormal Blood Chemistry Laboratory Values for Total Bilirubin, Creatinine, and Urea in Older Adults | 7 days (Day 8) and 1 month (Day 30) after first IMP injection, and 1 month (Day 394) after second IMP injection (revaccination |
| Proportion of Older Adult With Abnormal and Severe Abnormal Values for Hematology Laboratory Parameter | 7 days (Day 8) and 1 month (Day 30) after first IMP injection, and 1 month (Day 394) after second IMP injection (revaccination) |
| Proportion of Older Adult With Abnormal Values and Severe Abnormal Values for Blood Chemistry Laboratory Parameter | 7 days (Day 8) and 1 month (Day 30) after first IMP injection, and 1 month (Day 394) after second IMP injection (revaccination) |
| Proportion of Older Adult Participants With Solicited AEs | 7 days after 2nd IMP injection (revaccination, Day 364 to 371) |
| GMFI of RSV-A, RSV-B, hMPV-A, and hMPV-B Serum Neutralizing Antibody Titers in Older Adults | Pre-injection baseline to 6 months (Day 182) and 12 months (Day 364) after first IMP injection, and 1 month (Day 394), 6 months (Day 546), and 12 months (Day 720) after second IMP injection (revaccination) |
| Geometric Mean Titers (GMTs) of RSV-A, RSV-B, hMPV-A, and hMPV-B Serum Neutralizing Antibody Titers in Older Adults | Pre-injection baseline to 1 month (Day 30), 6 months (Day 182) and 12 months (Day 364) after first IMP injection, and 1 month (Day 394), 6 months (Day 546), and 12 months (Day 720) after second IMP injection (revaccination) |
| Proportion of Older Adult Participants with Sero-response Greater Than or Equal to (>=) 4-fold (SRR-4) and 8-fold (SRR-8) Increase from Baseline in Neutralizing Antibody Titers for RSV-A, RSV-B, hMPV-A and hMPV-B | Pre-injection baseline up to 1 month (Day 30), 6 months (Day 182) and 12 months (Day 364) after first IMP injection, and 1 month (Day 394), 6 months (Day 546), and 12 months (Day 720) after second IMP injection (revaccination) |
| GMFI of RSV Pre-fusion Protein (Pre-F) and hMPV Pre-F Serum Immunoglobulins G (IgG) Concentrations in Older Adults | Pre-injection baseline up to 1 month (Day 30), 6 months (Day 182) and 12 months (Day 364) after first IMP injection, and 1 month (Day 394), 6 months (Day 546), and 12 months (Day 720) after second IMP injection (revaccination) |
| Geometric Mean Concentrations (GMC) of Serum IgG Versus RSV Pre-F and hMPV Pre-F in Older Adults | Up to 1 month (Day 30), 6 months (Day 182), and 12 months (Day 364) after first IMP injection and 1 month (Day 394), 6 months (Day 546) and 12 months (Day 720) after second IMP injection (revaccination) |
| Geometric Mean Ratios (GMRs) of Fold Increase of RSV-A and RSV-B Neutralizing Serum Antibody Titers Versus Fold Increase of RSV Pre-F Serum IgG Concentration in Older Adults | Pre-injection baseline up to 1 month (Day 30), 6 months (Day 182) and 12 months (Day 364) after first IMP injection, and 1 month (Day 394), 6 months (Day 546), and 12 months (Day 720) after second IMP injection (revaccination) |
| GMR of Fold Increase of hMPV-A and hMPV-B Neutralizing Serum Antibody Titers Versus Fold Increase of hMPV Pre-F Serum IgG Concentration in Older Adults | Pre-injection baseline up to 1 month (Day 30), 6 months (Day 182) and 12 months (Day 364) after first IMP injection, and 1 month (Day 394), 6 months (Day 546), and 12 months (Day 720) after second IMP injection (revaccination) |
Countries
Australia
Outcome results
None listed