A Study to Assess the Safety, Reactogenicity and Immune Response of GlaxoSmithKline (GSK) Biologicals' Investigational Respiratory Syncytial Virus (RSV) Vaccine (GSK3844766A) in Older Adults

NCT03814590 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 2088512018-000849-38
• Study Type: interventional
• Target: 1,053
• Locations: 2 countries
• Sites: 21

Brief Summary

The purpose of this study is to assess the safety, reactogenicity and immune responses of two doses of the investigational RSV vaccines (with different formulations), when administered intramuscularly (IM) according to a 0, 2 month schedule, in older adults aged 60 to 80 years. As the investigational vaccines have not yet been tested in humans before, the study will first assess the safety, reactogenicity and immune responses in young adults aged 18 to 40 years. The study will thus be conducted in 2 parts (Part A and Part B).

Conditions

Respiratory Syncytial Virus Infections

Keywords

Respiratory syncytial virus (RSV); Vaccine; Safety; Reactogenicity; Immunogenicity

Outcome Measures

Primary Outcomes (13)

• Number of Subjects With Any Solicited Local Symptoms After First Vaccination Dose

  Assessed solicited local AEs at injection site are pain, erythema and swelling. Any erythema/swelling was scored as injection site erythema/swelling with a diameter larger than (\>) 20 millimeters (mm)

  During a 7-day follow-up period after first vaccination dose (i.e., on the day of vaccination [at Day 1] and 6 subsequent days)

• Number of Subjects With Any Solicited Local Symptoms After Second Vaccination Dose

  Assessed solicited local AEs at injection site are pain, erythema and swelling. Any erythema/swelling was scored as injection site erythema/swelling with a diameter larger than (\>) 20 millimeters (mm)

  During a 7-day follow-up period after second vaccination dose (i.e., on the day of vaccination [at Day 61] and 6 subsequent days)

• Number of Subjects With Any Solicited General Symptom After First Vaccination Dose

  Assessed solicited general symptoms include arthralgia, fatigue, fever \[defined as temperature equal to or above 38.0 degrees Celsius (°C)\], gastrointestinal symptoms \[nausea, vomiting, diarrhea and/or abdominal pain\], headache, myalgia and shivering.

  During a 7-day follow-up period after the first vaccination dose (i.e., on the day of vaccination [at Day 1] and 6 subsequent days)

• Number of Subjects With Any Solicited General Symptom After Second Vaccination Dose

  Assessed solicited general symptoms include arthralgia, fatigue, fever \[defined as temperature equal to or above 38.0 degrees Celsius (°C)\], gastrointestinal symptoms \[nausea, vomiting, diarrhea and/or abdominal pain\], headache, myalgia and shivering.

  During a 7-day follow-up period after the second vaccination dose (i.e., on the day of vaccination [at Day 61] and 6 subsequent days)

• Number of Subjects With Any Unsolicited Adverse Events (AEs) After Any Vaccination Dose

  An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and/or any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any is defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.

  During a 30-day follow-up period (i.e., on the day of vaccination and 29 subsequent days) after any vaccination dose (across doses)

• Number of Subjects Presenting Change From Baseline in Hematology and Biochemistry With Respect of Normal Laboratory Ranges, After First Vaccine Dose (Part A Groups)

  Assessed hematological laboratory parameters include basophils, eosinophils, erythrocytes, hemoglobin, lymphocytes, monocytes, neutrophils, platelets, white blood cells. Biochemical laboratory parameters include alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], creatinine, urea nitrogen and uric acid. Categories reported when comparing Day 1 (pre-vaccination dose 1=baseline) and Day 8 hematological and biochemical laboratory results are defined as follows: \<parameter\>-\<range at baseline\>-\<range at timing\> (e.g. ALT-Within-Within). Ranges level being classified as unknown, below, within or above the normal ranges.

  At baseline and at 7 days after the first vaccine dose (Day 8)

• Number of Subjects Presenting Change From Baseline in Hematology and Biochemistry With Respect of Normal Laboratory Ranges, After First Vaccine Dose (Part B Groups)

  Assessed hematological laboratory parameters include basophils, eosinophils, erythrocytes, hemoglobin, lymphocytes, monocytes, neutrophils, platelets, white blood cells. Biochemical laboratory parameters include alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], creatinine, urea nitrogen and uric acid. Categories reported when comparing Day 1 (pre-vaccination dose 1=baseline) and Day 8 hematological and biochemical laboratory results are defined as follows: \<parameter\>-\<range at baseline\>-\<range at timing\> (e.g. ALT-Within-Within). Ranges level being classified as unknown, below, within or above the normal ranges.

  At baseline and at 7 days after the first vaccine dose (Day 8)

• Number of Subjects Presenting Change From Baseline in Hematology and Biochemistry With Respect of Normal Laboratory Ranges, After Second Vaccine Dose (Part A Groups)

  Assessed hematological laboratory parameters include basophils, eosinophils, erythrocytes, hemoglobin, lymphocytes, monocytes, neutrophils, platelets, white blood cells. Biochemical laboratory parameters include alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], creatinine, urea nitrogen and uric acid. Categories reported when comparing Day 61 (pre-vaccination dose 2=baseline) and Day 68 hematological and biochemical laboratory results are defined as follows: \<parameter\>-\<range at baseline\>-\<range at timing\> (e.g. ALT-Within-Within). Ranges level being classified as unknown, below, within or above the normal ranges.

  At baseline and at 7 days after the second vaccine dose (Day 68)

• Number of Subjects Presenting Change From Baseline in Hematology and Biochemistry With Respect of Normal Laboratory Ranges, After Second Vaccine Dose (Part B Groups)

  Assessed hematological laboratory parameters include basophils, eosinophils, erythrocytes, hemoglobin, lymphocytes, monocytes, neutrophils, platelets, white blood cells. Biochemical laboratory parameters include alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], creatinine, urea nitrogen and uric acid. Categories reported when comparing Day 61 (pre-vaccination dose 2=baseline) and Day 68 hematological and biochemical laboratory results are defined as follows: \<parameter\>-\<range at baseline\>-\<range at timing\> (e.g. ALT-Within-Within). Ranges level being classified as unknown, below, within or above the normal ranges.

  At baseline and at 7 days after the second vaccine dose (Day 68)

• Number of Subjects With Any Grade 3 Non-serious AEs (Solicited and Unsolicited) After First Dose of Vaccination

  A Grade 3 AE is any AE assessed as severe, i.e. which prevents normal, everyday activities. In adults, such an AE would, for example, prevent attendance at work and would necessitate the administration of corrective therapy.

  During a 30-day follow-up period (i.e., on the day of vaccination at Day 1, and 29 subsequent days) after first dose of vaccination

• Number of Subjects With Any Grade 3 Non-serious AEs (Solicited and Unsolicited) After Second Dose of Vaccination

  A Grade 3 AE is any AE assessed as severe, i.e. which prevents normal, everyday activities. In adults, such an AE would, for example, prevent attendance at work and would necessitate the administration of corrective therapy.

  During a 30-day follow-up period (i.e., on the day of vaccination at Day 61, and 29 subsequent days) after second dose of vaccination

• Number of Subjects With Any Serious Adverse Events (SAEs) up to 30 Days After the Second Vaccination

  A SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization or results in disability/incapacity.

  From first vaccination (Day 1) up to 30 days post second vaccination (Day 91)

• Number of Subjects With Any Potential Immune-mediated Diseases (pIMDs) up to 30 Days After the Second Vaccination (Part B Groups)

  pIMDs are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology.

  From first vaccination (Day 1) up to 30 days post second vaccination (Day 91)

Secondary Outcomes (6)

• Number of Subjects With Any SAEs, up the End of Follow-up Period (Month 14) - Part B Groups

  From Day 1 up to the end of follow-up period (Month 14)

• Number of Subjects Reporting pIMDs up to the End of Follow-up Period (Month 14) - Part B Groups

  From Day 1 up to the end of follow-up period (Month 14)

• Number of Subjects With at Least One RSV-confirmed Respiratory Tract Infection (RTI) Episode Post-vaccination Reported During RTI Surveillance - Part B Groups

  During the RSV season (from October 2019 to March 2020)

• Humoral Immune Response With Respect to Components of the Investigational Vaccine in Terms of Neutralizing Antibody Titers Against RSV-serotype A

  At pre-vaccination (Day 1), 30 days post-Dose 1 (Day 31), on the day of second vaccination (Day 61) and 30 days post-Dose 2 (Day 91)

• Humoral Immune Response With Respect to Components of the Investigational Vaccine in Terms of RSVPreF3-specific Immunoglobulin G (IgG) Antibody Concentrations

  At pre-vaccination (Day 1), 30 days post-Dose 1 (Day 31), on the day of second vaccination (Day 61) and 30 days post-Dose 2 (Day 91)

Study Arms (14)

Group Low Dose_PLAIN_A

EXPERIMENTAL

Subjects in Part A, aged 18-40 years, receiving 2 doses of RSV Vaccine (GSK3844766A) unadjuvanted low dose on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Biological: RSV Vaccine (GSK3844766A) unadjuvanted low dose

Group Medium Dose_PLAIN_A

EXPERIMENTAL

Subjects in Part A aged 18-40 years, receiving 2 doses of RSV Vaccine (GSK3844766A) unadjuvanted medium dose, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Biological: RSV Vaccine (GSK3844766A) unadjuvanted medium dose

Group High Dose_PLAIN_A

EXPERIMENTAL

Subjects in Part A aged 18-40 years, receiving 2 doses of RSV Vaccine (GSK3844766A) unadjuvanted high dose, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Biological: RSV Vaccine (GSK3844766A) unadjuvanted high dose

Group Placebo_A

PLACEBO COMPARATOR

Subjects in Part A aged 18-40 years, receiving 2 doses of placebo (saline solution) control, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Drug: Placebo (Saline solution)

Group Low Dose_PLAIN_B

EXPERIMENTAL

Subjects in Part B aged 60-80 years, receiving 2 doses of RSV Vaccine (GSK3844766A) unadjuvanted low dose, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Biological: RSV Vaccine (GSK3844766A) unadjuvanted low dose

Group Low Dose_AS01E_B

EXPERIMENTAL

Subjects in Part B aged 60-80 years, receiving 2 doses of the RSV Vaccine (GSK3844766A) low dose adjuvanted with AS01E, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Biological: RSV Vaccine (GSK3844766A) low dose adjuvanted with AS01E

Group Low Dose_AS01B_B

EXPERIMENTAL

Subjects in Part B aged 60-80 years, receiving 2 doses of the RSV Vaccine (GSK3844766A) low dose adjuvanted with AS01B, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Biological: RSV Vaccine (GSK3844766A) low dose adjuvanted with AS01B

Group Medium Dose_PLAIN_B

EXPERIMENTAL

Subjects in Part B aged 60-80 years, receiving 2 doses of RSV Vaccine (GSK3844766A) unadjuvanted medium dose, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Biological: RSV Vaccine (GSK3844766A) unadjuvanted medium dose

Group Medium Dose_AS01E_B

EXPERIMENTAL

Subjects in Part B aged 60-80 years, receiving 2 doses of the RSV Vaccine (GSK3844766A) medium dose adjuvanted with AS01E, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Biological: RSV Vaccine (GSK3844766A) medium dose adjuvanted with AS01E

Group Medium Dose_AS01B_B

EXPERIMENTAL

Subjects in Part B aged 60-80 years, receiving 2 doses of the RSV Vaccine (GSK3844766A) medium dose adjuvanted with AS01B, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Biological: RSV Vaccine (GSK3844766A) medium dose adjuvanted with AS01B

Group High Dose_PLAIN_B

EXPERIMENTAL

Subjects in Part B aged 60-80 years, receiving 2 doses of RSV Vaccine (GSK3844766A) unadjuvanted high dose, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Biological: RSV Vaccine (GSK3844766A) unadjuvanted high dose

Group High Dose_AS01E_B

EXPERIMENTAL

Subjects in Part B aged 60-80 years, receiving 2 doses of the RSV Vaccine (GSK3844766A) high dose adjuvanted with AS01E, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Biological: RSV Vaccine (GSK3844766A) high dose adjuvanted with AS01E

Group High Dose_AS01B_B

EXPERIMENTAL

Subjects in Part B aged 60-80 years, receiving 2 doses of the RSV Vaccine (GSK3844766A) high dose adjuvanted with AS01B, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Biological: RSV Vaccine (GSK3844766A) high dose adjuvanted with AS01B

Group Placebo_B

PLACEBO COMPARATOR

Subjects in Part B aged 60-80 years, receiving 2 doses of placebo (saline solution) control, on a 0, 2 Months schedule, by IM injection into the deltoid region of the arm.

Drug: Placebo (Saline solution)

Interventions

RSV Vaccine (GSK3844766A) unadjuvanted low dose BIOLOGICAL

Two doses administered intramuscularly at Days 1 and 61 in the deltoid region of the arm

Group Low Dose_PLAIN_A; Group Low Dose_PLAIN_B

RSV Vaccine (GSK3844766A) low dose adjuvanted with AS01E BIOLOGICAL

Two doses administered intramuscularly at Days 1 and 61 in the deltoid region of the arm.

Group Low Dose_AS01E_B

RSV Vaccine (GSK3844766A) low dose adjuvanted with AS01B BIOLOGICAL

Two doses administered intramuscularly at Days 1 and 61 in the deltoid region of the arm

Group Low Dose_AS01B_B

RSV Vaccine (GSK3844766A) unadjuvanted medium dose BIOLOGICAL

Two doses administered intramuscularly at Days 1 and 61 in the deltoid region of the arm.

Group Medium Dose_PLAIN_A; Group Medium Dose_PLAIN_B

RSV Vaccine (GSK3844766A) medium dose adjuvanted with AS01E BIOLOGICAL

Two doses administered intramuscularly at Days 1 and 61 in the deltoid region of the arm.

Group Medium Dose_AS01E_B

RSV Vaccine (GSK3844766A) medium dose adjuvanted with AS01B BIOLOGICAL

Two doses administered intramuscularly at Days 1 and 61 in the deltoid region of the arm.

Group Medium Dose_AS01B_B

RSV Vaccine (GSK3844766A) unadjuvanted high dose BIOLOGICAL

Two doses administered intramuscularly at Days 1 and 61 in the deltoid region of the arm.

Group High Dose_PLAIN_A; Group High Dose_PLAIN_B

RSV Vaccine (GSK3844766A) high dose adjuvanted with AS01E BIOLOGICAL

Two doses administered intramuscularly at Days 1 and 61 in the deltoid region of the arm

Group High Dose_AS01E_B

RSV Vaccine (GSK3844766A) high dose adjuvanted with AS01B BIOLOGICAL

Two doses administered intramuscularly at Days 1 and 61 in the deltoid region of the arm.

Group High Dose_AS01B_B

Placebo (Saline solution) DRUG

Two doses administered intramuscularly at Days 1 and 61 in the deltoid region of the arm.

Group Placebo_A; Group Placebo_B

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For all subjects:
• Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
• Written informed consent obtained from the subject prior to performing any study specific procedure.
• For Part A:
• A male or female between, and including, 18 and 40 years of age at the time of the first vaccination.
• For Part B:
• A male or female between, and including, 60 and 80 years of age at the time of the first vaccination.
• Subjects with residence status allowing free mixing with general community or in an assisted-living facility that provides minimal assistance, such that the subject is primarily responsible for self-care and activities of daily living.

You may not qualify if:

• For all subjects:
• Use of any investigational or non-registered product other than the study vaccine during the period starting 30 days before the first dose of study vaccine, or planned use during the study period.
• Any medical condition that in the judgment of the investigator would make IM injection unsafe.
• Chronic administration of immunosuppressants or other immune-modifying drugs during the period starting 6 months prior to the first vaccine dose. For corticosteroids, this will mean prednisone (≥ 20 mg/day, or equivalent). Inhaled and topical steroids are allowed.
• Administration of long-acting immune-modifying drugs or planned administration at any time during the study period.
• Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the first dose and ending 30 days after the last dose of study vaccine administration, with the exception of inactivated and subunit influenza vaccines which can be administered up to 14 days before or from 30 days after each study vaccination.
• Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine.
• Hypersensitivity to latex.
• Serious or unstable chronic illness. Patients with chronic stable conditions with or without specific treatment, such as diabetes, hypertension or cardiac disease, are allowed to participate in this study.
• Any other condition (e.g. chronic obstructive pulmonary disease or severe respiratory condition) that, in the opinion of the investigator, might interfere with the evaluations required by the study.
• History of any neurological disorders or seizures.
• Acute disease and/or fever at the time of enrolment.
• Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by the investigator based on medical history, physical examination or laboratory screening tests.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (21)

GSK Investigational Site

Jacksonville, Florida, 32216, United States

Location

GSK Investigational Site

Miami, Florida, 33143, United States

Location

GSK Investigational Site

Stockbridge, Georgia, 30281, United States

Location

GSK Investigational Site

Lenexa, Kansas, 66219, United States

Location

GSK Investigational Site

Wichita, Kansas, 67207, United States

Location

GSK Investigational Site

Elkridge, Maryland, 21075, United States

Location

GSK Investigational Site

Kansas City, Missouri, 64114, United States

Location

GSK Investigational Site

Omaha, Nebraska, 68134, United States

Location

GSK Investigational Site

Rochester, New York, 14609, United States

Location

GSK Investigational Site

Hickory, North Carolina, 28602, United States

Location

GSK Investigational Site

Wilmington, North Carolina, 28401, United States

Location

GSK Investigational Site

Cleveland, Ohio, 44122, United States

Location

GSK Investigational Site

Medford, Oregon, 97504, United States

Location

GSK Investigational Site

Mt. Pleasant, South Carolina, 29464, United States

Location

GSK Investigational Site

Spartanburg, South Carolina, 29303, United States

Location

GSK Investigational Site

Fort Worth, Texas, 76135, United States

Location

GSK Investigational Site

Houston, Texas, 77081, United States

Location

GSK Investigational Site

San Antonio, Texas, 78229, United States

Location

GSK Investigational Site

Ghent, 9000, Belgium

Location

GSK Investigational Site

Leuven, 3000, Belgium

Location

GSK Investigational Site

Wilrijk, 2610, Belgium

Location

Related Publications (1)

• Leroux-Roels I, Davis MG, Steenackers K, Essink B, Vandermeulen C, Fogarty C, Andrews CP, Kerwin E, David MP, Fissette L, Vanden Abeele C, Collete D, de Heusch M, Salaun B, De Schrevel N, Koch J, Verheust C, Dezutter N, Struyf F, Mesaros N, Tica J, Hulstrom V. Safety and Immunogenicity of a Respiratory Syncytial Virus Prefusion F (RSVPreF3) Candidate Vaccine in Older Adults: Phase 1/2 Randomized Clinical Trial. J Infect Dis. 2023 Mar 28;227(6):761-772. doi: 10.1093/infdis/jiac327.

  PMID: 35904987 DERIVED

MeSH Terms

Conditions

Respiratory Syncytial Virus Infections

Interventions

Respiratory Syncytial Virus Vaccines; Saline Solution

Condition Hierarchy (Ancestors)

Pneumovirus Infections; Paramyxoviridae Infections; Mononegavirales Infections; RNA Virus Infections; Virus Diseases; Infections

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2019
• First Posted: January 24, 2019
• Study Start: January 21, 2019
• Primary Completion: December 12, 2019
• Study Completion: November 30, 2020
• Last Updated: August 5, 2022
• Results First Posted: March 23, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

BE (3); US (18)