A Study of Investigational RSV/hMPV Combination and Investigational hMPV Vaccines in Younger and Older Adults

Official title

A Phase 1/2, Randomized, Controlled, Observer-blind, Multicentre Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of GSK Biologicals' Investigational Respiratory Syncytial Virus (RSV)/Human Metapneumovirus (hMPV) Combination and Investigational hMPV Vaccines When Administered Intramuscularly According to a Single Dose Schedule in Younger Adults ≥18 to ≤49 Years and Older Adults Aged ≥60 to ≤80 Years

Overview

The aim of this study is to evaluate the safety, reactogenicity, and immune response of the different formulations of the investigational RSV/hMPV combination vaccine and investigational hMPV vaccine in younger and older adults.

Interventions

• Biological RSV/hMPV_V low dose vaccine
  RSV/hMPV\_V low dose vaccine administered intramuscularly.
• Biological RSV/hMPV_V medium dose vaccine
  RSV/hMPV\_V medium dose vaccine administered intramuscularly.
• Biological RSV/hMPV_V high dose vaccine
  RSV/hMPV\_V high dose vaccine administered intramuscularly.
• Biological RSV/hMPV_W low dose vaccine
  RSV/hMPV\_W low dose vaccine administered intramuscularly.
• Biological RSV/hMPV_W medium dose vaccine
  RSV/hMPV\_W medium dose vaccine administered intramuscularly.
• Biological RSV/hMPV_W high dose vaccine
  RSV/hMPV\_W high dose vaccine administered intramuscularly.
• Biological RSV/hMPV_X low dose vaccine
  RSV/hMPV\_X low dose vaccine administered intramuscularly.
• Biological RSV/hMPV_X medium dose vaccine
  RSV/hMPV\_X medium dose vaccine administered intramuscularly.
• Biological RSV/hMPV_X high dose vaccine
  RSV/hMPV\_X high dose vaccine administered intramuscularly.
• Biological hMPV_Y low dose vaccine
  hMPV\_Y low dose vaccine administered intramuscularly.

Primary outcome measures

• Number of Participants Reporting Solicited Administration Site Events [Time frame: Day 1 to Day 7]
• Number of Participants Reporting Solicited Systemic Events [Time frame: Day 1 to Day 7]
• Number of Participants Reporting Unsolicited Adverse Events (AEs) [Time frame: Day 1 to Day 30]
• Number of Participants Reporting Medically Attended Adverse Events (MAAEs) [Time frame: Day 1 to Month 12]
• Number of Participants Reporting Potential immune-mediated disorders (pIMDs) [Time frame: Day 1 to Month 12]
• Number of Participants Reporting Serious Adverse Events (SAEs) [Time frame: Day 1 to study end [Month 24 for OA groups (only the selected formulation group&its comparators), Month 12 for YA groups & OA groups (all other investigational vaccine formulation groups not selected for future clinical development&other comparators)]]
• Number of Participants Reporting Hematological and Biochemical Laboratory Abnormalities [Time frame: At Day 1 (pre-vaccination) in Phase 1 groups]
• Number of Participants Reporting Hematological and Biochemical Laboratory Abnormalities [Time frame: At Day 8 (post-vaccination) in Phase 1 groups]

Secondary outcome measures (12)

• Number of participants with hMPV neutralization titers equal to or above (>=) the assay cut-off value [Time frame: At Day 1 (pre-vaccination), Day 8 and Day 31 in Phase 1 and Phase 2 OA groups]
• Geometric mean titers (GMTs) of hMPV neutralization titers [Time frame: At Day 1 (pre-vaccination), Day 8 and Day 31 in Phase 1 and Phase 2 OA groups]
• Mean geometric increase (MGI) of hMPV neutralization titers [Time frame: At Day 8 and Day 31 compared to Day 1 (pre-vaccination) in Phase 1 and Phase 2 OA groups]
• Seroresponse rate (SRR) against hMPV [Time frame: At Day 8 and Day 31 compared to Day 1 (pre-vaccination) in Phase 1 and Phase 2 OA groups]
• Number of participants with RSV-A neutralization titers >= assay cut-off value [Time frame: At Day 1 (pre-vaccination), Day 8 and Day 31 in Phase 1 and Phase 2 OA groups]
• GMTs of RSV-A neutralization titers [Time frame: At Day 1 (pre-vaccination), Day 8 and Day 31 in Phase 1 and Phase 2 OA groups]
• MGI of RSV-A neutralization titers [Time frame: At Day 8 and Day 31 compared to Day 1 (pre-vaccination) in Phase 1 and Phase 2 OA groups]
• SRR against RSV-A [Time frame: At Day 8 and Day 31 compared to Day 1 (pre-vaccination) in Phase 1 and Phase 2 OA groups]
• Number of participants with RSV-B neutralization titers >= assay cut-off value [Time frame: At Day 1 (pre-vaccination), Day 8 and Day 31 in Phase 1 and Phase 2 OA groups]
• GMTs of RSV-B neutralization titers [Time frame: At Day 1 (pre-vaccination), Day 8 and Day 31 in Phase 1 and Phase 2 OA groups]
• MGI of RSV-B neutralization titers [Time frame: At Day 8 and Day 31 compared to Day 1 (pre-vaccination) in Phase 1 and Phase 2 OA groups]
• SRR against RSV-B [Time frame: At Day 8 and Day 31 compared to Day 1 (pre-vaccination) in Phase 1 and Phase 2 OA groups]

Eligibility criteria

Inclusion criteria

Participants are eligible to be included in the study only if all of the following criteria apply:

• Written informed consent obtained from the participant prior to performance of any study-specific procedure.
• Participants who can and will comply with the requirements of the protocol (e.g., completion of the eDiary, return for follow-up visits, ability to access and utilize a phone or other electronic communications).
• Note: For OA participants, in case of physical incapacity that would preclude the self-completion of the eDiaries, either site staff can assist the participant (for activities performed during site visits) and/or the participant may assign a caregiver to assist him/her with this activity (for activities performed at home). However, at no time will the site staff or caregiver evaluate the participant's health status while answering eDiaries or make decisions on behalf of the participant.
• Body Mass Index (BMI) between 18 kg/m\^2 and 33 kg/m\^2, inclusive.

Specific inclusion criteria for OA

• A male or female between and including, 60 to 80 YOA at the time of the study intervention administration.
• Healthy participants or medically stable patients as established by medical history, physical examination (and normal screening laboratory tests including Grade 1 laboratory abnormalities that are not-clinically significant in Phase 1 only).

Specific inclusion criteria for YA

• A male or female participant between and including 18 to 49 YOA at the time of the study intervention administration.
• Healthy participants as established by medical history, clinical examination and laboratory assessment at screening.
• Participants of non-childbearing potential may be enrolled in the clinical study.
• Participant of childbearing potential may be enrolled in the study if the participant:

• has used two methods of contraception, at-least one of which must be a highly effective method, and the other being male condom for male sexual partners of POCBP to be used during sexual intercourse (with the exception of sexual abstinence, vasectomized partner and male partner who has been sterilized, in which case contraception is not required), at-least 30 days prior to study intervention administration, and has agreed to continue using above contraception requirements for 8 weeks after study intervention administration.
• has a negative serum pregnancy test at screening and negative urine pregnancy test prior to study intervention administration on Day 1.

Exclusion criteria

Participants are excluded from participating in the study if any of the following criteria apply:

• History of any reaction or hypersensitivity likely to be exacerbated by any component of the study intervention(s).
• Any medical condition that in the judgment of the investigator would make IM injection unsafe.
• Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease (e.g., current malignancy, HIV) or immunosuppressive/cytotoxic therapy (e.g., medication used during cancer chemotherapy, organ transplantation, or to treat autoimmune disorders), based on medical history and physical examination (no laboratory testing required).
• Acute or unstable chronic pulmonary, cardiovascular, hepatic, or renal functional abnormality, as determined by physical examination and medical history.
• Documented history of HIV, HBV, HCV infection.
• History of RSV and /or hMPV-associated illness, diagnosed serologically or microbiologically in the last 12 months.
• Recurrent history or uncontrolled neurological disorders or seizures, or history of demyelinating conditions (including GBS).
• Any history of dementia or any medical condition that moderately or severely impairs cognition.
• Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the clinical study.
• Significant underlying illness that in the opinion of the investigator would be expected to prevent completion of the study (e.g., life-threatening disease).
• Use of any investigational or non-registered product (drug, vaccine, or invasive medical device) other than the study intervention during the period beginning 30 days before study intervention administration (Day -29 to Day 1), or within 5 half-lives, whichever is longer, or their planned use during the study period.
• Has previously received an investigational or approved vaccine or antibody for prevention of hMPV and/or RSV-associated diseases.
• Chronic administration of immune-modifying drugs (defined as more than 14 consecutive days in total) and/or planned use of long-acting immune-modifying treatments at any time up to the end of the study.

• Up to 3 months prior to the study intervention administration:

• For corticosteroids, this will mean prednisone equivalent >=20 mg/day for adult participants. Inhaled, topical and intra-articular steroids are allowed.
• Administration of immunoglobulins and/or any blood products or plasma derivatives.
• Up to 6 months prior to study intervention administration: long-acting immune-modifying drugs including among others immunotherapy (e.g., TNF-inhibitors), monoclonal antibodies, antitumoral medication.
• Concurrently participating in another clinical study, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational intervention.
• History of chronic alcohol consumption and/or drug abuse as deemed by the investigator to render the potential participant unable/unlikely to provide accurate safety reports or comply with study procedures.
• Participation of any study personnel or their immediate dependents, family, or household members.
• Planned move during the study period that will prohibit participating in the study until study end.
• Bedridden participants.

Specific exclusion criteria for OA population

• Planned or actual administration of a vaccine not foreseen by the study protocol in the period beginning 30 days before study intervention administration (Day - 29 to Day 1), or their planned use 30 days after study intervention administration, with the exception of inactivated, subunit and split influenza vaccines or COVID-19 vaccines which can be administered up to 14 days before or from 14 days after the study intervention administration.
• At screening (Phase 1 only): Any laboratory abnormality. Grade 1 laboratory abnormalities that are not-clinically significant\* may be included in the study.

• The investigators should use their clinical judgment to decide which abnormalities are clinically significant.

Specific exclusion criteria for YA population

• Pregnant or lactating participant.
• Female planning to become pregnant or planning to discontinue contraceptive precautions for 8 weeks after study intervention administration.
• Planned or actual administration of a vaccine not foreseen by the study protocol in the period beginning 30 days before study intervention administration (Day - 29 to Day 1), or their planned use 30 days after study intervention administration.
• At screening: Any hematologic and/or biochemical laboratory abnormality.
• Use of any medication, including prescription and non-prescription drugs or herbal remedies (such as St. John's wort) beginning 14 days (or 5 half-lives) prior to study intervention administration and/or planned administration during the study period. Certain medications may be permitted (Eg: contraceptives for POCBP).

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

Sequential

Masking

Quadruple blind

Primary purpose

Prevention

Study locations

United States · 2 centers

• GSK Investigational Site — Lenexa
• GSK Investigational Site — Seattle

Australia · 2 centers

• GSK Investigational Site — Botany
• GSK Investigational Site — Camberwell

Identifiers

NCT: NCT07628049 · 223960 · 2025-524456-58

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗