A Study to Characterize the Safety and Immunogenicity of AZD6489 in Participants 60 Years of Age and Older (ARIES)

Official title

A Phase I/II, Randomized, Double-Blind, Active-Controlled Study to Characterize the Safety and Immunogenicity of AZD6489 in Adults 60 Years of Age and Older

Overview

This Phase I/II study is to characterize the safety and immunogenicity of 2 dose levels of AZD6489, an investigational RSV recombinant prefusion F protein VLP vaccine.

Detailed description

This Phase I/II clinical study will be conducted in the US at approximately 5 sites. The study is a randomized, double-blind, active-controlled study to characterize the safety and immunogenicity of a single dose of AZD6489 in adults ≥ 60 years of age. Two dose levels of AZD6489 will be assessed.

Approximately 160 participants will be randomized and stratified by age group and previous receipt of RSV vaccine. Participants will be randomized/dosed to receive AZD6489, licensed RSV vaccine #1, or licensed RSV vaccine #2. The study is split into 2 cohorts based on the 2 dose levels of AZD6489 being studied.

For each cohort, an initial sentinel group of 8 participants will be followed up for safety via a telephone or teleconference call, approximately 48 hours post-study intervention, and the safety data will be evaluated by the SRC in order to provide a recommendation to continue randomization and vaccination for the remaining participants in that cohort.

An ESDR of all available safety data through 7 days post-vaccination of Cohort 1 will be conducted. Randomization of Cohort 2 will be allowed only after the ESDR of Cohort 1 participants has been completed and the results support that the safety profile is acceptable.

This study includes 5 in-clinic study visits. The duration of each participant's involvement in the study will be approximately 12 months following the administration of study intervention. Safety will be assessed for the duration of the study. Blood will be taken for immunological and safety assessments as per SoA.

Interventions

• Biological AZD6489
  Participants will receive AZD6489 as a single intramuscular injection.
• Biological Licensed RSV vaccine #1
  Participants will receive licensed RSV vaccine #1 as a single intramuscular injection.
• Biological Licensed RSV vaccine #2
  Participants will receive licensed RSV vaccine #2 as a single intramuscular injection.

Primary outcome measures

• Incidence of immediate unsolicited adverse events (AEs) [Time frame: 30 minutes post-study intervention]
• Incidence of injection site and systemic solicited adverse reactions (ARs) [Time frame: Day 1 through 7 days post-study intervention]
• Incidence of unsolicited adverse events (AEs) [Time frame: Day 1 through 28 days post-study intervention]
• Incidence of serious adverse events (SAEs) [Time frame: Day 1 to Day 365]
• Incidence of adverse events of special interest (AESIs) [Time frame: Day 1 to Day 365]
• Incidence of medically attended adverse events (MAAEs) [Time frame: Day 1 to Day 365]
• RSV A nAb responses to AZD6489 [Time frame: Day 29]

Eligibility criteria

Inclusion criteria

• Participant must be ≥ 60 years of age at the time of signing the informed consent.
• Participants who are medically stable in the opinion of the Investigator at the time of study intervention. Participants with chronic stable medical conditions with or without specific treatment, such as diabetes, hypertension, or cardiac disease, are allowed to participate in this study if considered by the Investigator as medically stable.
• Able to understand and comply with study requirements/procedures including attending all scheduled study visits (if applicable, with assistance by caregiver, surrogate, or legally authorized representative or equivalent representative as locally defined) based on the assessment of the Investigator.
• Capable of giving signed informed consent as described in Appendix A 3 which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.

Exclusion criteria

• Previous known laboratory-confirmed RSV infection within 6 months of Visit 1.
• Moderate to severe acute (time-limited) or any febrile (temperature ≥ 38.0 °C \[100.4 ºF\]) illness/infection within 3 days of Visit 1; participants excluded for transient acute illness may be rescreened once and vaccinated if the illness has resolved.
• History of a clinically significant bleeding disorder contraindicating IM injections or venipuncture based on Investigator judgment.
• History of hypersensitivity to any component of the study interventions.
• History of severe adverse reaction or severe allergic reaction (eg, anaphylaxis) associated with any vaccine.
• Known chronic hepatitis B or C.
• Known or suspected congenital or acquired immunodeficiency.
• History of Guillain-Barré syndrome or any other demyelinating condition.
• Current or previous (within the past 5 years) history of any malignancy (except treated non-melanoma skin cancers, locally treated cervical cancer, or prostate cancer that is stable at the time of vaccination in the absence of therapy).
• Chronic illness that, in the opinion of the Investigator, is at a stage where it might interfere with study conduct or completion.
• Receipt of any licensed or investigational RSV vaccine within 2 years prior to Visit 1, or planned receipt during the study.
• Receipt of any licensed vaccine (including licensed influenza or COVID-19 vaccines) within 28 days prior to Visit 1 or expected receipt prior to end of Visit 3 assessments.
• Receipt of immunoglobulin or blood products within 3 months prior to Visit 1, or planned receipt during the study.
• Receipt of immune-modifying drugs or immunosuppressive therapy (eg, anti-cancer chemotherapy, anti-cytokine therapy, or radiation therapy) within 6 months prior to Visit 1, or planned receipt during study.
• Long-term systemic corticosteroid therapy (prednisone or equivalent at a dose of ≥ 20 mg daily or every other day for more than 2 consecutive weeks) within 6 months prior to Visit 1 or planned receipt during study. Topical/inhaled/intra-articular/ophthalmic/otic steroids or short-term oral steroids are permitted.
• Receipt of allergen immunotherapy if dose has been escalated or reduced within 30 days of Visit 1. Allergen immunotherapy is allowed if participant is receiving stable desensitization therapy for at least 30 days prior to Visit 1 and there is no anticipated change before Visit 3.
• Participation in another clinical study with a study intervention administered in the preceding 90 days (or preceding 6 months for extended half-life drug products) or expected receipt of another study intervention during the study, or concurrent participation in another interventional study. Individuals who are in a prolonged post-administration observation period of another investigational, marketed drug, or non-interventional clinical study, for which there is no ongoing exposure to the investigational or marketed product and all scheduled on-site visits are completed, will be allowed to take part in this study, if all other eligibility criteria are met.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Prevention

Study locations

United States · 6 centers

• Research Site — Long Beach
• Research Site — Rolling Hills Estates
• Research Site — Chicago
• Research Site — Lenexa
• Research Site — Kansas City
• Research Site — Omaha

Identifiers

NCT: NCT07717840 · D7280C00001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗