Arexvy (RSVPreF3) vaccine for people with weakened immune systems

Immunogenicity and Safety of Multiple-Dose Adjuvanted RSVPreF3 (Arexvy®) Vaccination Among Immunocompromised Persons

This trial will test whether one or two doses of the Arexvy RSV vaccine help people with weakened immune systems make protective immune responses and will track side effects.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 170 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Johns Hopkins University (other)
• Drugs / interventions: Rituximab, ocrelizumab, ofatumumab, belimumab, epratuzumab, CAR-T, Chimeric antigen receptor, prednisone
• Locations: 1 site (Baltimore, Maryland)
• Trial ID: NCT07050732 on ClinicalTrials.gov

What this trial studies

Adults with weakened immune systems (including stem-cell, CAR-T, or solid organ transplant recipients) are randomized to receive either one Arexvy dose followed by placebo or two Arexvy doses 60 days apart, with all immunocompromised participants receiving a further Arexvy dose one year after the first. Participants keep a 7-day symptom diary after each vaccination and attend three in-person visits plus six phone follow-ups over 1.5 years for blood tests and safety monitoring. A small group of healthy adults will also be enrolled to receive a single Arexvy dose for comparison. The study’s main aims are to compare immune responses between the dosing schedules and to record adverse events.

Who should consider this trial

Good fit: Adults (≥18) who are medically stable with weakened immune systems—such as autologous or allogeneic stem cell transplant recipients, CAR-T recipients, or solid organ transplant recipients—with expected survival of at least one year and ability to attend study visits.

Not a fit: People without a weakened immune system, those who are medically unstable, or those with life expectancy under one year are unlikely to gain benefit from this study’s findings or participation.

Why it matters

Potential benefit: If successful, the results could identify a dosing schedule that gives better RSV protection for immunocompromised adults and inform vaccination recommendations for this vulnerable group.

How similar studies have performed: Arexvy (RSVPreF3) has shown immune responses and protection signals in older adults, but evidence in immunocompromised populations is limited, so this approach builds on prior adult data but is not yet well tested in these patients.

Eligibility criteria

Inclusion Criteria:

* Able to understand and provide informed consent
* Willing and able to comply with the requirements and restrictions in the protocol, including study visits and study-related procedures
* Medically stable in the opinion of the Investigator at the time of first study vaccination
* Life expectancy ≥ 365 days in the opinion of the Investigator at the time of first study vaccination
* Included in at least one of the groups below:

  1. Cellular therapy recipients (CTR):

     * Individuals ≥ 18 years of age at the time of first study vaccination
     * History of at least one of the following: i. Autologous stem cell transplant received more than 90 days prior to first study vaccination, ii. Allogeneic stem cell transplant received more than 90 days prior to first study vaccination, iii. Chimeric antigen receptor T cell (CAR-T) therapy received more than 90 days prior to first study vaccination
  2. Solid organ transplant recipients (SOTR):

     * Individuals ≥ 18 years of age at the time of first study vaccination
     * Received an ABO-compatible, single-organ type, solid organ transplant (lung, heart, kidney, liver) at least 90 days prior to first study vaccination, and are on at least 2 systemic immunosuppressive agents at time of first study vaccination
  3. Healthy comparator (HC):

     * Individuals ≥ 60 years of age at the time of first study vaccination or 50-59 years of age at the time of first study vaccination and at increased risk of severe RSV disease
     * No history of (a) or (b) above, and considered healthy or with chronic and stable medical conditions in the opinion of the Investigator, without immune compromise
* Participants of childbearing potential if practicing adequate contraception or abstinence from 1 month prior to first study vaccination and agree to continue adequate contraception or abstinence through at least 1 month after last study vaccination. All participants of childbearing potential must have a negative pregnancy test on the day of first study vaccination, prior to administration.

Exclusion Criteria:

* Known history of hypersensitivity to any vaccine or history of a life-threatening reaction to a vaccine
* Previous vaccination with any licensed or investigational RSV vaccine
* Acute or chronic clinically significant/unstable neurological disease (such as uncontrolled seizures, strokes, Guillain-Barré Syndrome (GBS)
* Vaccination with any inactivated, subunit, or split influenza vaccine or COVID-19 vaccine within 14 days prior to first study vaccination, or vaccination with any other licensed or investigational vaccine within 30 days prior to first study vaccination
* Receipt of investigational or approved monoclonal antibodies against RSV within 90 days prior to first study vaccination
* Moderate or severe acute illness/infection (in opinion of the Investigator) or febrile illness (temperature ≥ 38.0°C \[≥ 100.4°F\]) on the day of first study vaccination. A prospective participant should not be enrolled in the study until the condition has resolved or the febrile event has subsided.
* Any medical condition that in the opinion of the Investigator would make intramuscular injection unsafe
* Receipt of immunoglobulins or plasma products within 90 days prior to first study vaccination
* Receipt of B-cell depleting medications (e.g., Rituximab, ocrelizumab, ofatumumab, belimumab, epratuzumab, antithymocyte globulin) within 90 days prior to first study vaccination
* Currently pregnant or breastfeeding or planning to become pregnant, discontinue contraception, or breastfeed during the study period
* Any of the following:

  1. Cellular therapy recipients (CTR):

     * Graft-versus-host disease (GVHD) requiring systemic treatment with at least 0.5 mg/kg per day of prednisone or equivalent at time of first study vaccine
  2. Solid organ transplant recipients (SOTR):

     * History of any of the following within 90 days prior to first study vaccination: allograft rejection, post-transplant lymphoproliferative disease, treatment for either of these conditions
  3. Healthy comparator (HC):

     * Any confirmed/suspected immunosuppressive or immunodeficient condition resulting from disease or immunosuppressive or cytotoxic therapy, based on medical history
* Any other conditions which, in the opinion of the Investigator, may pose additional risks from participation in the study, may interfere with the individual's ability to comply with study requirements or may impact the quality or interpretation of the data obtained from the study

Where this trial is running

Baltimore, Maryland

• Johns Hopkins University — Baltimore, Maryland, United States (RECRUITING)

Study contacts

• Principal investigator: John Baddley, MD — Johns Hopkins University
• Study coordinator: John Baddley, MD

Conditions: Respiratory Syncytial Virus