Clinical trial NCT05842967: A Study to Assess the Safety, Tolerability, and Immunogenicity of RSVpreF in Adults at High Risk of Severe RSV Disease
Official title: A PHASE 3 PROTOCOL TO EVALUATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF RESPIRATORY SYNCYTIAL VIRUS (RSV) PREFUSION F SUBUNIT VACCINE IN ADULTS AT HIGH RISK OF SEVERE RSV DISEASE
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: RESPIRATORY SYNCYTIAL VIRUS (RSV)
Keywords: RESPIRATORY SYNCYTIAL VIRUS (RSV)
ADULTS AT HIGH RISK
IMMUNOCOMPROMISED ADULTS
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2023-05-06
Enrollment: 886
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Substudy A: Phase 3, multicenter, randomized, double-blinded, placebo-controlled study that will assess the safety, tolerability, and immunogenicity of Pfizer's RSVpreF in adults 18 to \<60 years of age considered to be at high risk of RSV disease due to certain chronic medical conditions. Approximately 675 participants ≥18 to \<60 years of age considered at high risk of RSV disease due to certain chronic medical conditions, excluding immunocompromising conditions, will be randomized to receive a single 120-µg dose of RSVpreF or placebo in a 2:1 ratio.

Substudy B: Phase 3, single-arm, open-label, multicenter study that will assess the safety, tolerability, and immunogenicity of Pfizer's RSVpreF in immunocompromised adults. Approximately 200 immunocompromised adults ≥18 years of age will receive 2 120-µg doses of RSVpreF with an interval of 1 month. Approximately 100 participants will be ≥60 years of age and approximately 100 participants will be ≥18 to 60 years of age.
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to learn about the safety and immunogenicity of a study vaccine (called RSVpreF) in several adult groups. Respiratory Syncytial Virus (RSV) is a common type of virus (germ) that can cause severe illness, where medical help is needed. RSV can lead to airway diseases in all ages. Vaccines help your body make antibodies which help fight against diseases. This is called an immune response. This study will measure how much antibody participants make after receiving RSVpreF (immunogenicity).

The study consists of 2 groups (Substudy A and Substudy B).

Substudy A is seeking approximately 675 participants who are:

* Between 18 and 60 years of age.
* Considered having a high likelihood of severe RSV disease due to certain long-term medical conditions. Such medical conditions do not include immunocompromising conditions.

Participants will need to come to the study clinic at least 2 times. At the first clinic visit, participants will receive 1 shot of RSVpreF or placebo in the arm by chance. A placebo looks like the study vaccine but contains no active ingredients. At each clinic visit, a blood sample will be taken. A third (final) visit can be either completed in clinic or via telephone contact. This study is about 6 months long for each participant.

Substudy B is seeking approximately 200 participants who are:

* At least 18 years of age. About half of the participants will be at least 60 years of age.
* Considered having a weakened immune system (immunocompromised). Participants will need to come to the study clinic at least 3 times. All participants will receive a shot of RSVpreF at the first study clinic visit. The second study clinic visit will be 1 month later. All participants will receive a second shot of the study vaccine at this second study clinic visit. Blood samples will be taken at the 3 study clinic visits. A fourth (final) visit can be either completed in clinic or via telephone contact. This study is about 7 months long for each participant.

Detailed description: This is a Phase 3 protocol that will assess the safety, tolerability, and immunogenicity of Pfizer's RSVpreF in adults at high risk of severe RSV disease. Each substudy design is detailed separately, and these substudies may be conducted in parallel, as required by the clinical plan, within the framework of this protocol.

Substudy A Design:

This is a Phase 3, multicenter, randomized, double-blinded, placebo-controlled study that will assess the safety, tolerability, and immunogenicity of Pfizer's RSVpreF in adults 18 to \<60 years of age considered to be at high risk of RSV disease due to certain chronic medical conditions.

Approximately 675 participants ≥18 to \<60 years of age considered at high risk of RSV disease due to certain chronic medical conditions, excluding immunocompromising conditions, will be randomized to receive a single 120-µg dose of RSVpreF or placebo in a 2:1 ratio. Enrollment will be monitored to help ensure distribution of vaccination across the age range. The duration of study participation for each participant will be 6 months, with 3 scheduled visits.

All participants will have blood drawn at baseline prior to vaccination and at 1 month after vaccination to assess immunogenicity. Immunogenicity elicited at 1 month after vaccination with RSVpreF in Substudy A will be bridged to the immunogenicity of participants 60 years of age and older in the C3671013 study, in which RSVpreF efficacy was demonstrated.

Local reaction and systemic event data will be collected in an e-diary for 7 days after study vaccination (Days 1 through 7, where Day 1 is the day of vaccination). Reported Grade 3 reactogenicity will be assessed by the study site to determine if an unscheduled visit is required.

For all participants, AEs will be collected from informed consent through 1 month following study intervention administration, and AESIs, NDCMCs and SAEs will be collected from informed consent throughout study participation. In addition, AEs occurring up to 48 hours after blood draws that are related to study procedures will be collected.

Substudy B Design:

This is a Phase 3, single-arm, open-label, multicenter study that will assess the safety, tolerability, and immunogenicity of Pfizer's RSVpreF in immunocompromised adults.

Substudy B included approximately 200 immunocompromised adults ≥18 years of age, that will receive 2 120-µg doses of RSVpreF with an interval of 1 month. Approximately 100 participants will be ≥60 years of age and approximately 100 participants will be ≥18 to 60 years of age. Enrollment will be monitored to help ensure distribution of vaccination across the age ranges and underlying immunocompromising conditions. The duration of study participation for each participant will be 7 months, with 4 scheduled visits. All participants will have blood drawn at baseline prior to vaccination and at 1 month after (each) vaccination to assess immunogenicity.

Local reaction and systemic event data will be collected in an e-diary for 7 days after study vaccination (Days 1 through 7, where Day 1 is the day of vaccination). Reported Grade 3 reactogenicity will be assessed by the study site to determine if an unscheduled visit is required.

For all participants, AEs will be collected from informed consent through 1 month following the last study intervention administration, and AESIs, NDCMCs and SAEs will be collected from informed consent throughout study participation. In addition, AEs occurring up to 48 hours after blood draws that are related to study procedures will be collected.

Eligibility criteria: Substudy A Inclusion Criteria:

1. Capable of giving signed informed consent as described per protocol.
2. Participants ≥18 to \<60 years of age at study enrollment.
3. Life expectancy ≥12 months (365 days) in the opinion of the investigator at enrollment.
4. Participants who are willing and able to comply with all scheduled visits, vaccination plan, lifestyle considerations, and other study procedures.
5. Participants who are considered at high risk of RSV disease by virtue of the following:

   * Adults with chronic pulmonary (including asthma), cardiovascular (excluding isolated hypertension), renal, hepatic, neurologic, hematologic, or metabolic disorders (including diabetes mellitus).

Chronic medical conditions for this substudy are defined as:

- Duration greater than 6 months.

* Stable disease not requiring a significant change in therapy in the previous 6 weeks or hospitalization for worsening disease within 12 weeks before receipt of study intervention.
* Requires regular medical follow-up or ongoing medication or hospitalization in the previous year.

  • Additional groups at high risk include:
* Residents of nursing homes and other long-term care facilities.

Substudy A Exclusion Criteria:

1. Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
2. History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s) or any related vaccine.
3. Participants who do not have adequate deltoid muscle mass to allow intramuscular vaccination, in the opinion of the investigator.
4. Serious chronic disorder, including metastatic malignancy, end-stage renal disease with or without dialysis, clinically unstable cardiac disease, or any other disorder that, in the investigator's opinion, excludes the participant from participating in the study.
5. Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.
6. Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.

   Note: Specific criteria for participants with known stable infection with HIV can be found in protocol.
7. Individuals who receive chronic systemic treatment with immunosuppressive therapy, including cytotoxic agents, immunosuppressive monoclonal antibodies, systemic corticosteroids\*, eg, for cancer or an autoimmune disease, or radiotherapy, from 60 days before study intervention administration or planned receipt throughout the study.

   \*Applies to systemic corticosteroids administered for ≥14 days at a dose of ≥20 mg/day of prednisone or equivalent (eg, for cancer or an autoimmune disease). Systemic corticosteroids administered at a dose of \<20 mg/day of prednisone or equivalent are permitted. Inhaled/nebulized, intra-articular, intrabursal, or topical (skin, eyes, or ears) corticosteroids are permitted.
8. Receipt of blood/plasma products or immunoglobulin within 60 days before study intervention administration or planned receipt of these medications prior to the final blood draw.

   Note: Monoclonal antibodies with targeted mechanisms of action used in the management of chronic illnesses (eg, migraine headaches, osteoporosis) are permitted, provided they do not meet exclusion criterion 7.
9. Previous vaccination with any licensed or investigational RSV vaccine or planned receipt during study participation.
10. Participation in other studies involving an investigational product within 28 days prior to consent and/or through and including the 6-month follow-up visit.
11. Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members.

Substudy B Inclusion Criteria

1. Capable of giving signed informed consent as described per protocol.
2. Participants ≥18 years of age at study enrollment.
3. Life expectancy ≥12 months (365 days) in the opinion of the investigator at enrollment.
4. Participants who are willing and able to comply with all scheduled visits, vaccination plan, lifestyle considerations, and other study procedures.
5. Participants who are immunocompromised by virtue of the following:

   •Having known advanced NSCLC with at least 1 of the following:
   * Has received initial or maintenance chemotherapy at least 2 weeks (14 days) before enrollment (or is treatment-naïve), and is not expected to receive chemotherapy within at least 2 weeks (14 days) after dose administration of initial vaccination or second vaccination; and/or
   * Is receiving checkpoint inhibitor treatment (PD-1/PD-L1 inhibitor, CTLA-4 inhibitor) and has undergone at least 1 treatment cycle prior to enrollment; or
   * Is receiving targeted drug therapy (EGFR, ALK, ROS1, BRAF, RET, MET, NTRK inhibitors) and has undergone at least 1 treatment cycle prior to enrollment.

   OR - Is currently undergoing maintenance hemodialysis treatment secondary to end-stage renal disease . OR - Is on active immunomodulator therapy (eg, TNFα inhibitor, tofacitinib, or MTX) for an autoimmune inflammatory disorder (eg, inflammatory arthritis, such as rheumatoid arthritis, psoriatic arthritis, and juvenile idiopathic arthritis, or inflammatory bowel disease, such as ulcerative colitis or Crohn's disease) at a stable\*dose.

   \*Stable dose is defined as receiving the same dose for at least 3 months (84 days) with no changes in the 28 days prior to enrollment. See protocol for details on stable dose for MTX.

   OR - Is receiving an SOT (kidney, liver, lung, or heart) at least 3 months (84 days) prior to enrollment (Visit 201) and with no acute rejection episodes within 2 months (60 days) prior to enrollment (Visit 201).

   Substudy B Exclusion Criteria:

1.Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.

2.History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s) or any related vaccine.

3.Participants with a history of transplant rejection, or PTLD, or participants who have had treatment for these conditions within 3 months (84 days) prior to study enrollment.

4.Participants who do not have adequate deltoid muscle mass to allow intramuscular vaccination, in the opinion of the investigator.

5.Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.

Note: Specific criteria for participants with known stable infection with HIV can be found in protocol.

6.Receipt of investigational or approved monoclonal antibodies against RSV within 6 months before study intervention administration.

7.Receipt of blood/plasma products or immunoglobulin (IVIG, SCIG) within 60 days before study intervention administration or planned receipt of these medications prior to the final blood draw.

Note: Please see the inclusion criteria in the protocol regarding criteria for targeted immunoglobulin therapies for underlying medical conditions.

Note: Monoclonal antibodies with targeted mechanisms of action used in the management of chronic illnesses (eg, migraine headaches, osteoporosis) are permitted.

8.Previous vaccination with any licensed or investigational RSV vaccine or planned receipt during study participation.

9.Participation in other studies involving an investigational product within 28 days prior to consent and/or through and including the 6-month follow-up visit.

10.Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members.

Primary outcomes:
measure: Substudy A: Primary Safety - The proportion of participants reporting local reactions
timeFrame: Within 7 days following study administration intervention
measure: Substudy A: Primary Safety - The proportion of participants reporting systemic reactions
timeFrame: Within 7 days following study administration intervention
measure: Substudy A: Primary Safety - The proportion of participants reporting adverse events
timeFrame: Through 1 month following study administration intervention
measure: Substudy A: Primary Safety - The proportion of participants reporting newly diagnosed chronic medical conditions
timeFrame: Throughout the study duration (an average of 6 months)
measure: Substudy A: Primary Safety - The proportion of participants reporting serious adverse events
timeFrame: Throughout the study duration (an average of 6 months)
measure: Substudy A: Primary Immunogenicity - GMT ratio, estimated by the ratio of the geometric mean titers for RSV A and RSV B serum NTs with RSVpreF in Study C3671023 participants to that in Study C3671013 adults ≥60 years of age.
timeFrame: 1 month after vaccination
measure: Substudy A: Primary Immunogenicity - Difference in seroresponse rate of RSV A and RSV B serum neutralizing titers at 1 month after vaccination with RSVpreF between participants in Study C3671023 and in Study C3671013
timeFrame: 1 month after vaccination
measure: Substudy B: Primary Safety - The proportion of participants reporting local reactions
timeFrame: Within 7 days following study administration intervention
measure: Substudy B: Primary Safety - The proportion of participants reporting systemic reactions
timeFrame: Within 7 days following study administration intervention
measure: Substudy B: Primary Safety - The proportion of participants reporting adverse events
timeFrame: Through 1 month following the last dose of study intervention administration
measure: Substudy B: Primary Safety - The proportion of participants reporting newly diagnosed chronic medical donditions
timeFrame: Throughout the study duration (an average of 7 months)
measure: Substudy B: Primary Safety - The proportion of participants reporting serious adverse events
timeFrame: Throughout the study duration (an average of 7 months)
measure: Substudy B: Primary Immunogenicity - Geometric mean titers of neutralizing titers for RSV A and RSV B
timeFrame: At each blood sampling visit (Day 1, 1-month after vaccination 1, 1-month after vaccination 2)
measure: Substudy B: Primary Immunogenicity - Geometric mean fold rise of neutralizing titers for RSV A and RSV B
timeFrame: From before vaccination to each postvaccination blood sampling visit (Day 1, 1-month after vaccination 1, 1-month after vaccination 2)
Secondary outcomes:
measure: Substudy A: Secondary Immunogenicity - Geometric mean titers of neutralizing titers for RSV A and RSV B
timeFrame: At each blood sampling visit (Day 1 and 1-month after vaccination)
measure: Substudy A: Secondary Immunogenicity - Geometric mean fold rise of neutralizing titers for RSV A and RSV B
timeFrame: From before vaccination to the postvaccination blood sampling visit (Day 1 and 1-month after vaccination)
Other outcomes:
Locations:
city: Athens
country: United States
facility: North Alabama Research Center
state: Alabama
city: Birmingham
country: United States
facility: Central Research Associates
state: Alabama
city: Huntsville
country: United States
facility: Medical Affiliated Research Center
state: Alabama
city: Phoenix
country: United States
facility: HOPE Research Institute
state: Arizona
city: Phoenix
country: United States
facility: The Pain Center of Arizona (IP Storage Location)
state: Arizona
city: Phoenix
country: United States
facility: The Pain Center of Arizona
state: Arizona
city: Tempe
country: United States
facility: HOPE Research Institute
state: Arizona
city: Lake Forest
country: United States
facility: Orange County Research Center
state: California
city: Los Angeles
country: United States
facility: Kaiser Permanente
state: California
city: Tustin
country: United States
facility: Orange County Research Center
state: California
city: Walnut Creek
country: United States
facility: Diablo Clinical Research, Inc.
state: California
city: Bridgeport
country: United States
facility: New England Research Associates, LLC
state: Connecticut
city: Washington
country: United States
facility: GW Medical Faculty Associates
state: District of Columbia
city: Washington
country: United States
facility: GW Vaccine Research Unit
state: District of Columbia
city: Coral Gables
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Florida
city: Fort Lauderdale
country: United States
facility: Proactive Clinical Research,LLC
state: Florida
city: Orlando
country: United States
facility: Clinical Neuroscience Solutions - Orlando - South Delaney Avenue
state: Florida
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Wichita
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Kansas
city: New Orleans
country: United States
facility: DelRicht Research
state: Louisiana
city: Baltimore
country: United States
facility: Institute of Human Virology (IHV)
state: Maryland
city: Baltimore
country: United States
facility: University of Maryland, Baltimore, Institute of Human Virology
state: Maryland
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Silver Spring
country: United States
facility: Jadestone Clinical Research
state: Maryland
city: Springfield
country: United States
facility: Bio-Kinetic Clinical Applications, LLC dba QPS-MO
state: Missouri
city: Springfield
country: United States
facility: Bio-Kinetic Clinical Applications, LLD dba QPS-MO
state: Missouri
city: Springfield
country: United States
facility: Bio-Kinetic Clinical Applications LLC dba QPS-MO (Patient Screening Only)
state: Missouri
city: Bozeman
country: United States
facility: Bozeman Health Deaconess Hospital
state: Montana
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Omaha
country: United States
facility: University Of Nebraska Medical Center
state: Nebraska
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: Rochester
country: United States
facility: Rochester Clinical Research, LLC
state: New York
city: Wilmington
country: United States
facility: Accellacare - Wilmington
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Knoxville
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Tennessee
city: Austin
country: United States
facility: Orion Clinical Research
state: Texas
city: Plano
country: United States
facility: AIM Trials, LLC
state: Texas
city: Red Oak
country: United States
facility: Epic Medical Research
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas, LLC
state: Texas
city: Charlottesville
country: United States
facility: Charlottesville Medical Research
state: Virginia
city: Norfolk
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Virginia
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: