Healthy Participants
Conditions
Keywords
Respiratory syncytial virus (RSV), Human metapneumovirus (hMPV)
Brief summary
The primary purpose of this study is to assess the immunogenicity and safety of IVX-A12 in adults 60 years of age and older.
Detailed description
This is a randomized, modified double-blind, active controlled study to characterize the immunogenicity and safety of IVX-A12. Approximately 140 participants will be randomized in a 1:1 ratio to receive IVX-A12 (approximately 70) or licensed respiratory syncytial virus (RSV) vaccine (AREXVY) (approximately 70). The study is planned to be conducted at approximately 5 sites in the United States. The duration of each participant's involvement in the study will be approximately 6 months following administration of study vaccination.
Interventions
BIOLOGICALIVX-A12
IVX-A12 IM injection.
BIOLOGICALLicensed RSV Vaccine
Licensed RSV Vaccine (AREXVY) IM injection.
Sponsors
Icosavax, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Adults \>=60 years of age at the time of signing informed consent. 2. Participants who are medically stable according to the judgment of the Investigator. 3. Able to understand and comply with study requirements/procedures based on the assessment of the Investigator. 4. Capable of giving signed informed consent.
Exclusion criteria
1. Acute (time-limited) or febrile (temperature \>=38.0 °C \[100.4 ºF\]) illness/infection within 3 days of planned dosing. 2. History of a clinically significant bleeding disorder (e.g., factor deficiency, coagulopathy, or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venipuncture. 3. History of hypersensitivity to any component of the study vaccination. 4. History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (e.g., anaphylaxis). 5. Known or suspected congenital or acquired immunodeficiency. 6. Known or suspected autoimmune condition as determined by history and/or physical examination. 7. History of Guillain-Barré syndrome or any other demyelinating condition. 8. History of malignancy other than treated non-melanoma skin cancers or locally-treated cervical cancer in previous 5 years. 9. Any condition that may significantly increase the risk to the participant because of participation in the study, impact the participant's ability to participate in the study, or impair the interpretation of the study data. 10. Receipt of any licensed or investigational RSV and/or Human metapneumovirus (hMPV) vaccine any time prior to administration of study intervention. 11. Receipt of any licensed vaccine (other than licensed influenza or COVID-19 vaccines) within 28 days prior to or expected receipt within 28 days after administration of study intervention. Licensed influenza or COVID-19 vaccines are permitted beginning greater than (\>)14 days prior to and \>14 days after administration of study intervention. 12. Receipt of immunoglobulin or blood products within 3 months prior to administration of study intervention or expected receipt during the study. 13. Receipt of immune-modifying drugs or immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy within 6 months prior to enrollment (or expected receipt during study), or long-term systemic corticosteroid therapy (prednisolone or equivalent at a dose of \>=20 mg daily or every other day for more than 2 consecutive weeks) within 6 months prior to study intervention or anticipated receipt during study. 14. Participation in another study or receiving interventional study investigational medicinal product (IMP), in the preceding 28 days or expected receipt of another study intervention (or participation in another study) during the period of study follow-up. 15. Employees of the Sponsor involved in planning, executing, supervising, or reviewing the IVX-A12 program, clinical study site staff, or any other individuals involved with the conduct of the study, or immediate family members of such individuals. 16. Alcohol or substance abuse that, in the opinion of the Investigator, might interfere with the study conduct or completion. 17. Deprived of freedom by an administrative or court order, or in emergency setting, or hospitalized involuntarily. 18. Judgment by the Investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Model-adjusted Geometric Mean Concentration (GMC) for RSV/A Neutralizing Antibodies (NAb) | At Day 29 | Model-adjusted GMCs and 95% CIs were derived using an ANCOVA model for log2 nAb responses at Day 29 with independent variables of study intervention, log2 baseline response, and age group. Measured values were calculated as the anti-logarithm transformation of the least square means and 95% CIs from the model. |
| Geometric Mean Fold Rise (GMFR) in RSV/A NAb Concentrations | From baseline up to Day 29 | The GMFR was calculated as the anti-logarithm of Σ(log2 transformed (post-baseline response/baseline response)/n), where n is the number of participants with non-missing response information at baseline and at the post-baseline timepoint. |
| Number of Participants With Immediate Unsolicited Adverse Events (AEs) | Within the 30 minutes after vaccination on Day 1 | Immediate AEs were defined as having an onset time within 30 minutes after study vaccination. |
| Number of Participants With Injection Site and Systemic Solicited Adverse Reactions (ARs) | Day 1 through Day 8 | The injection site solicited ARs included predefined injection site pain, injection site erythema/redness, and injection site swelling. The systemic solicited ARs included predefined fever, chills, headache, myalgia (muscle aches and pains), and fatigue (physical or mental tiredness). |
| Number of Participants With Unsolicited Adverse Events (AEs) | Day 1 through Day 29 | The unsolicited AEs were any AE other than predefined solicited AEs. |
| Number of Participants With Serious Adverse Events (SAEs), Medically-attended Adverse Events (MAAEs), and Adverse Events of Special Interests (AESIs) | Day 1 through Day 29 | A SAE defined as an AE that occurred during any phase of study and met one or more of following criteria: resulted in death; was immediately life-threatening; required in-patient hospitalization or led to prolongation of existing hospitalization; resulted in persistent or significant disability or incapacity; was a congenital anomaly or birth defect; or was considered an important medical event that might have jeopardized the participant or required medical intervention to prevent one of aforementioned outcomes. MAAEs defined as AEs leading to medically-attended visits that were not routine visits for physical examination or vaccination, such as an emergency room visit, or an otherwise unscheduled visit to or from medical personnel (medical doctor) for any reason. An AESI was an event of scientific and medical interest, specific to further understanding of safety profile of investigational vaccine and required close monitoring and rapid communication by Investigators to the Sponsor. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited at 5 investigative sites in the United States.
Pre-assignment details
A total 143 participants were enrolled and randomized to receive vaccinations in this study.
Participants by arm
| Arm | Count |
|---|---|
| IVX-A12 Participants received a single dose of 300 mcg IVX-A12, IM injection on Day 1. | 71 |
| AREXVY Participants received a single dose of 120 mcg AREXVY, IM injection on Day 1. | 72 |
| Total | 143 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 0 |
| Overall Study | Other | 1 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 0 |
Baseline characteristics
| Characteristic | AREXVY | Total | IVX-A12 |
|---|---|---|---|
| Age, Continuous | 66.6 years STANDARD_DEVIATION 5.6 | 66.7 years STANDARD_DEVIATION 5.7 | 66.8 years STANDARD_DEVIATION 5.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants | 27 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 57 Participants | 115 Participants | 58 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants | 33 Participants | 19 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 56 Participants | 105 Participants | 49 Participants |
| Sex: Female, Male Female | 38 Participants | 74 Participants | 36 Participants |
| Sex: Female, Male Male | 34 Participants | 69 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 71 | 0 / 72 |
| other Total, other adverse events | 6 / 71 | 15 / 72 |
| serious Total, serious adverse events | 2 / 71 | 1 / 72 |
Outcome results
Primary
Geometric Mean Fold Rise (GMFR) in RSV/A NAb Concentrations
The GMFR was calculated as the anti-logarithm of Σ(log2 transformed (post-baseline response/baseline response)/n), where n is the number of participants with non-missing response information at baseline and at the post-baseline timepoint.
Time frame: From baseline up to Day 29
Population: IAS included all participants in the SAF who had no eligibility-related protocol deviations judged to have the potential to interfere with the generation or interpretation of an immune response. Here, Overall Number of Participants Analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| IVX-A12 | Geometric Mean Fold Rise (GMFR) in RSV/A NAb Concentrations | 3.4 fold rise |
| AREXVY | Geometric Mean Fold Rise (GMFR) in RSV/A NAb Concentrations | 6.5 fold rise |
Primary
Model-adjusted Geometric Mean Concentration (GMC) for RSV/A Neutralizing Antibodies (NAb)
Model-adjusted GMCs and 95% CIs were derived using an ANCOVA model for log2 nAb responses at Day 29 with independent variables of study intervention, log2 baseline response, and age group. Measured values were calculated as the anti-logarithm transformation of the least square means and 95% CIs from the model.
Time frame: At Day 29
Population: Immunogenicity analysis set (IAS) included all participants in the SAF who had no eligibility-related protocol deviations judged to have the potential to interfere with the generation or interpretation of an immune response. Here, Overall Number of Participants Analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| IVX-A12 | Model-adjusted Geometric Mean Concentration (GMC) for RSV/A Neutralizing Antibodies (NAb) | 5910.4 internation unit per milliliter (IU/mL) |
| AREXVY | Model-adjusted Geometric Mean Concentration (GMC) for RSV/A Neutralizing Antibodies (NAb) | 10500.4 internation unit per milliliter (IU/mL) |
Primary
Number of Participants With Immediate Unsolicited Adverse Events (AEs)
Immediate AEs were defined as having an onset time within 30 minutes after study vaccination.
Time frame: Within the 30 minutes after vaccination on Day 1
Population: The SAF included all randomized participants who received one dose of study intervention, irrespective of their protocol adherence and continued participation in the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IVX-A12 | Number of Participants With Immediate Unsolicited Adverse Events (AEs) | 0 Participants |
| AREXVY | Number of Participants With Immediate Unsolicited Adverse Events (AEs) | 0 Participants |
Primary
Number of Participants With Injection Site and Systemic Solicited Adverse Reactions (ARs)
The injection site solicited ARs included predefined injection site pain, injection site erythema/redness, and injection site swelling. The systemic solicited ARs included predefined fever, chills, headache, myalgia (muscle aches and pains), and fatigue (physical or mental tiredness).
Time frame: Day 1 through Day 8
Population: The SAF included all randomized participants who received one dose of study intervention, irrespective of their protocol adherence and continued participation in the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IVX-A12 | Number of Participants With Injection Site and Systemic Solicited Adverse Reactions (ARs) | Solicited injection site AR | 14 Participants |
| IVX-A12 | Number of Participants With Injection Site and Systemic Solicited Adverse Reactions (ARs) | Solicited systemic AR | 19 Participants |
| AREXVY | Number of Participants With Injection Site and Systemic Solicited Adverse Reactions (ARs) | Solicited injection site AR | 31 Participants |
| AREXVY | Number of Participants With Injection Site and Systemic Solicited Adverse Reactions (ARs) | Solicited systemic AR | 17 Participants |
Primary
Number of Participants With Serious Adverse Events (SAEs), Medically-attended Adverse Events (MAAEs), and Adverse Events of Special Interests (AESIs)
A SAE defined as an AE that occurred during any phase of study and met one or more of following criteria: resulted in death; was immediately life-threatening; required in-patient hospitalization or led to prolongation of existing hospitalization; resulted in persistent or significant disability or incapacity; was a congenital anomaly or birth defect; or was considered an important medical event that might have jeopardized the participant or required medical intervention to prevent one of aforementioned outcomes. MAAEs defined as AEs leading to medically-attended visits that were not routine visits for physical examination or vaccination, such as an emergency room visit, or an otherwise unscheduled visit to or from medical personnel (medical doctor) for any reason. An AESI was an event of scientific and medical interest, specific to further understanding of safety profile of investigational vaccine and required close monitoring and rapid communication by Investigators to the Sponsor.
Time frame: Day 1 through Day 29
Population: The SAF included all randomized participants who received one dose of study intervention, irrespective of their protocol adherence and continued participation in the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IVX-A12 | Number of Participants With Serious Adverse Events (SAEs), Medically-attended Adverse Events (MAAEs), and Adverse Events of Special Interests (AESIs) | SAEs | 2 Participants |
| IVX-A12 | Number of Participants With Serious Adverse Events (SAEs), Medically-attended Adverse Events (MAAEs), and Adverse Events of Special Interests (AESIs) | MAAEs | 1 Participants |
| IVX-A12 | Number of Participants With Serious Adverse Events (SAEs), Medically-attended Adverse Events (MAAEs), and Adverse Events of Special Interests (AESIs) | AESIs | 0 Participants |
| AREXVY | Number of Participants With Serious Adverse Events (SAEs), Medically-attended Adverse Events (MAAEs), and Adverse Events of Special Interests (AESIs) | SAEs | 1 Participants |
| AREXVY | Number of Participants With Serious Adverse Events (SAEs), Medically-attended Adverse Events (MAAEs), and Adverse Events of Special Interests (AESIs) | MAAEs | 9 Participants |
| AREXVY | Number of Participants With Serious Adverse Events (SAEs), Medically-attended Adverse Events (MAAEs), and Adverse Events of Special Interests (AESIs) | AESIs | 0 Participants |
Primary
Number of Participants With Unsolicited Adverse Events (AEs)
The unsolicited AEs were any AE other than predefined solicited AEs.
Time frame: Day 1 through Day 29
Population: The SAF included all randomized participants who received one dose of study intervention, irrespective of their protocol adherence and continued participation in the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IVX-A12 | Number of Participants With Unsolicited Adverse Events (AEs) | 5 Participants |
| AREXVY | Number of Participants With Unsolicited Adverse Events (AEs) | 11 Participants |