A Phase III, open-label, randomized, controlled, multi-country study to evaluate the immune response, safety and reactogenicity of RSVPreF3 OA investigational vaccine when co-administered with 20-valent pneumococcal conjugate vaccine (PCV20) in adults aged 60 years and older.
- Trial ID
- 2022-501988-40-00
- Protocol
- 219276
- Sponsor
- GlaxoSmithKline Biologicals
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this Phase III, open-label, randomized, controlled, multi-country study is to demonstrate the **non-inferiority** of the 20-valent pneumococcal conjugate vaccine (**PCV20**) when co-administered with the RSVPreF3 OA investigational vaccine compared to PCV20 administered alone. Additionally, the study aims to demonstrate the non-inferiority of the RSVPreF3 OA investigational vaccine in terms of RSV-A and RSV-B neutralization antibodies when co-administered with PCV20 compared to the RSVPreF3 OA investigational vaccine administered alone. This is clinically relevant as it evaluates the potential for simultaneous administration of these vaccines in adults aged 60 years and older, which could enhance vaccination strategies against **RSV-associated disease** and pneumococcal infections in this population.
Secondary objectives include:
- Evaluating the humoral immune response to the RSVPreF3 OA investigational vaccine when co-administered with PCV20 or administered alone.
- Assessing the safety and reactogenicity following administration of the RSVPreF3 OA investigational vaccine and PCV20, whether co-administered or administered alone.
Participants
The clinical trial involves a total of **735 participants** who are adults aged **60 years and older**. The study population includes both **male and female** subjects, and participants are required to be medically stable, as determined by the investigator, at the time of the first study intervention. Individuals with chronic stable medical conditions such as diabetes mellitus, hypertension, or cardiac disease are eligible to participate if deemed stable. Participants are selected based on their ability to comply with the study protocol, including the completion of an electronic diary and attending follow-up visits. They must reside in the general community or in an assisted-living facility that provides minimal assistance, allowing them to be primarily responsible for their self-care and daily activities. The trial does not include a vulnerable population, and all participants have provided written or witnessed informed consent prior to any study-specific procedures. The study focuses on **RSV-associated disease** in this age group, with the aim of evaluating the non-inferiority of the investigational vaccines when co-administered.
Plans and Procedures
The clinical trial is a **Phase III**, open-label, randomized, controlled, multi-country study designed to evaluate the immune response, safety, and reactogenicity of an investigational vaccine for **respiratory syncytial virus** (RSV) when co-administered with a 20-valent pneumococcal conjugate vaccine (PCV20) in adults aged 60 years and older. The trial aims to demonstrate the non-inferiority of PCV20 when co-administered with the RSV investigational vaccine compared to PCV20 administered alone, as well as the non-inferiority of the RSV investigational vaccine in terms of RSV-A and RSV-B neutralization antibodies when co-administered with PCV20 compared to the RSV investigational vaccine administered alone. The trial is expected to conclude by June 27, 2024, with recruitment having started on August 7, 2023.
Participants will be involved in the study for a period of approximately six months, with the primary endpoint being the measurement of opsonophagocytic antibody titers for each pneumococcal vaccine serotype, and RSV-A and RSV-B neutralizing antibody titers, one month after the respective vaccine doses. Secondary endpoints include the mean geometric increase of RSV-A and RSV-B neutralizing antibody titers over baseline, and the percentage of participants reporting solicited and unsolicited adverse events, serious adverse events, and potential immune-mediated diseases up to the end of the study.
The study visits are structured as follows: an initial inclusion (screening) visit to assess eligibility based on criteria such as age, medical stability, and ability to comply with study requirements. This is followed by the administration of the study interventions and subsequent follow-up visits to monitor safety and collect data on immune response. The end-of-study visit will occur six months after the last vaccination to assess long-term safety and efficacy outcomes. Participants may be withdrawn from the study early if they experience significant adverse events, are unable to comply with study procedures, or withdraw consent.
Treatment
The clinical trial involves the administration of two experimental medications. The first medication is **Apexxnar**, a pneumococcal polysaccharide conjugate vaccine (20-valent, adsorbed), provided as a suspension for injection in a pre-filled syringe. This vaccine is designed to protect against pneumococcal disease and contains pneumococcal polysaccharide serotypes conjugated to CRM197 and adsorbed on aluminum phosphate. The pharmaceutical form is a suspension for injection, and it is administered via the **intramuscular** route. The dosage is 0.5 ml per administration, with a maximum treatment period of one day. The vaccine is manufactured by Pfizer Europe MA EEIG and is not a pediatric formulation.
The second experimental medication is a recombinant respiratory syncytial virus (RSV) pre-fusion F protein vaccine, adjuvanted with AS01E. This vaccine is also provided as a suspension for injection and is administered intramuscularly. The dosage is 0.5 ml per administration, with a maximum treatment period of one day. The vaccine is produced by GlaxoSmithKline Biologicals S.A. and is not a pediatric formulation. The investigational vaccine aims to elicit an immune response against RSV, specifically targeting RSV-A and RSV-B neutralization antibodies.
In this clinical trial, the primary objective is to evaluate the immune response, safety, and reactogenicity of the RSVPreF3 OA investigational vaccine when co-administered with the 20-valent pneumococcal conjugate vaccine (PCV20) in adults aged 60 years and older. The study aims to demonstrate the non-inferiority of PCV20 when co-administered with the RSVPreF3 OA investigational vaccine compared to PCV20 administered alone. Additionally, the trial seeks to demonstrate the non-inferiority of the RSVPreF3 OA investigational vaccine in terms of RSV-A and RSV-B neutralization antibodies when co-administered with PCV20 compared to the RSVPreF3 OA investigational vaccine administered alone.
Efficacy
Efficacy in this clinical trial will be assessed through several primary and secondary endpoints. The primary endpoints include the measurement of **opsonophagocytic (OP) antibody titers** for each pneumococcal vaccine serotype, expressed as between groups geometric mean titer (GMT) ratio, one month after the PCV20 dose. Additionally, the trial will evaluate RSV-A and RSV-B neutralizing antibody titers, also expressed as between groups GMT ratio, one month after the administration of the RSVPreF3 OA investigational vaccine.
Secondary endpoints will focus on the RSV-A and RSV-B neutralizing antibody titers, expressed as mean geometric increase (MGI) over baseline, one month post-vaccination. The trial will also monitor the percentage of participants reporting solicited events within seven days post-vaccination, unsolicited adverse events (AEs) within 30 days, serious adverse events (SAEs) from Day 1 up to the end of the study (EoS), and potential immune-mediated diseases (pIMDs) from Day 1 up to EoS, which is six months after the last vaccination.
Inclusion and Exclusion Criteria
Inclusion Criteria
- A male or female ≥60 YOA at the time of the first study intervention administration.
- Participants who, in the opinion of the investigator, 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). o Note: In case of physical incapacity that would preclude the self-completion of the eDiary, either site staff can assist the participant (for activities performed during site visits) 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 diaries or make decisions on behalf of the participant. *A ‘caregiver’ is a person who has a continuous caring role for a participant or may be a person having substantial periods of contact with a participant and/or is engaged in his/her daily health care (e.g., a relative of the participant including family members or friends).
- Written or witnessed informed consent obtained from the participant prior to any study-specific procedure being performed.
- Participants living in the general community or in an assisted-living facility that provides minimal assistance, such that the participant is primarily responsible for self care and activities of daily living.
- Participants who are medically stable in the opinion of the investigator at the time of first study intervention administration. Participants with chronic stable medical conditions with or without specific treatment, such as diabetes mellitus, hypertension, or cardiac disease, are allowed to participate in this study if considered by the investigator as medically stable.
Exclusion Criteria
- Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease (e.g., current malignancy, human immunodeficiency virus) or immunosuppressive/cytotoxic therapy, based on medical history and physical examination.
- History of any reaction or hypersensitivity (e.g., anaphylaxis) likely to be exacerbated by the study interventions, in particular any history of severe allergic reaction to any vaccine containing diphtheria toxoid, or PPSV23.
- Participants considered by investigator as suffering from serious or unstable chronic illness.
- Any history of dementia or any medical condition that moderately or severely impairs cognition.
- Recurrent or uncontrolled neurological disorders or seizures. Participants with medically controlled chronic neurological diseases can be enrolled in the study as per investigator assessment, provided that their condition will allow them to comply with the requirements of the protocol.
- Significant underlying illness that in the opinion of the investigator would be expected to prevent completion of the study.
- Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe.
- History of previous vaccination with any licensed or investigational pneumococcal conjugate vaccine, or planned receipt through study participation.
- History of previous vaccination with any licensed or investigational pneumococcal polysaccharide vaccine in the last 5 years from enrollment, or planned receipt through study participation.
- Previous vaccination with any licensed or investigational RSV vaccine
- Use of any investigational or non-registered product (drug, vaccine or medical device) other than the study interventions during the period beginning 30 days before the first dose of study interventions and ending 30 days after the last study intervention administration, or their planned use during the study period.
- Planned or actual administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the first study intervention administration and ending 30 days after the last study intervention administration. o Planned or actual administration of adjuvanted quadrivalent influenza vaccine or live influenza vaccine not foreseen by the study protocol in the period starting 30 days before the first study intervention administration and ending 30 days after the last study intervention administration.
- Administration of long-acting immune-modifying drugs or planned administration at any time during the study period.
- Administration of immunoglobulins and/or any blood products or plasma derivatives during the period starting 90 days before the administration of first dose of study interventions or planned administration during the study period.
- Chronic administration (defined as more than 14 consecutive days in total) of immunosuppressants or other immune-modifying drugs during the period starting 90 days prior to the first study intervention dose or planned administration during the study period. For corticosteroids, this will mean prednisone ≥20 mg/day, or equivalent. Inhaled and topical steroids are allowed.
- •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 vaccine/product (drug or invasive medical device).
- 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.
- Bedridden participants.
- Planned move during the study conduct that prohibits participation until study end.
- Participation of any study personnel or their immediate dependents, family, or household members.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Recruiting | 07 Aug 2023 | 91 |
 Poland | Not Recruiting | 07 Aug 2023 | 152 |
 Spain | Not Recruiting | 07 Aug 2023 | 164 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Apexxnar suspension for injection in pre-filled syringe Pneumococcal polysaccharide conjugate vaccine20-valent, adsorbed | Other | SUSPENSION FOR INJECTION IN PRE-FILLED SYRINGE | INTRAMUSCULAR | 0.5 | 1 | PRD9495859 |