Clinical trial NCT04138056: A Study of a Vaccine Against Respiratory Syncytial Virus (RSV) When Given Alone and Together With a Vaccine Against Diphtheria, Pertussis and Tetanus (Tdap) Viruses Followed by a 2nd Dose of the RSV Vaccine to Healthy Non-Pregnant Women
Official title: A Phase II Study of a Primary Dose of Investigational RSV Maternal Vaccine, Given Alone or With Boostrix, With a 2nd Dose Investigational RSV Maternal Vaccine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Respiratory Syncytial Virus Infections
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2019-10-24
Enrollment: 509
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to evaluate the safety, ability of GSK Biologicals' investigational RSV maternal vaccine (RSVPreF3) to generate an immune response and the degree to which the vaccine can cause side effects, when administered alone and in combination with Boostrix vaccine in healthy non-pregnant women 18-45 years of age. Two dose levels of RSVPreF3 and 2 Boostrix \[Diphtheria, Tetanus and acellular Pertussis (dTpa) vaccine\] formulations (US and ex-US) will be evaluated. A 2nd dose of RSVPreF3 will be administered in an extension of the study to assess the durability of the immune response after the first dose vaccination, and to assess the safety and immunogenicity following a second dose vaccination of the RSVPreF3 maternal vaccine.


Eligibility criteria: Inclusion Criteria:

Primary study

* Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
* Written or witnessed/thumb printed informed consent obtained from the subject prior to performance of any study specific procedure.
* Healthy female subjects; as established by medical history and clinical examination, aged 18 to 45 years at the time of the 1st vaccination;
* Female subjects of childbearing potential may be enrolled in the study, if the subject:

  * has practiced adequate contraception for 30 days prior to primary vaccination, and
  * has a negative pregnancy test on the day of primary vaccination, and
  * has agreed to continue adequate contraception for 90 days after completion of the vaccination.
* No local condition precluding injection in both left and right deltoid muscles.

Extension study

* Completed primary study and received 1st dose of a study vaccine.
* Written or witnessed/thumb printed informed consent obtained from the subject prior to performance of any study specific procedure to the study extension.

All subjects must satisfy ALL the following criteria:

* Subjects who can and will comply with the requirements of the protocol.
* Female subjects remain healthy; as established by medical history and clinical examination, aged 18 to 45 years at the time of the 1st vaccination;
* Female subjects of childbearing potential are eligible for the extension, if the subject:

  * has practiced adequate contraception for 30 days prior to 2nd vaccination
  * has a negative pregnancy test with results available on the day of 2nd vaccination
  * has agreed to continue adequate contraception for 90 days after completion of the 2nd vaccination.

Exclusion Criteria:

Primary study

Medical conditions

* History of any reaction/hypersensitivity likely to be exacerbated by any vaccines' component;
* Any confirmed/suspected immunosuppressive/immunodeficient condition, based on medical history and physical examination;
* Hypersensitivity to latex;
* Major congenital defects;
* Acute/chronic clinically significant pulmonary, cardiovascular, hepatic/renal functional abnormality;
* Significant/uncontrolled psychiatric illness;
* Recurrent history/uncontrolled neurological disorders/seizures;
* Documented HIV-positive subject;
* History of/current autoimmune disease;
* Body mass index (BMI)\>40 kg/m\^2;
* Any clinically significant hematological parameter and/or biochemical laboratory abnormality.
* Any other clinical condition that might pose additional risk to the subject due to participation in the study.

Prior/Concomitant therapy

* Use of any investigational/non-registered product other than the study vaccines during the period starting 30 days before 1st vaccination, or planned use during the study;
* Administration of long-acting immune-modifying drugs at any time during the study;
* Administration of immunoglobulins and/or any blood products/plasma derivatives during the period starting 3 months before the 1st vaccination or planned administration during the study;
* Chronic administration of immunosuppressants/other immune-modifying drugs during the period starting 3 months prior to 1st vaccine dose(s). For corticosteroids, this will mean prednisone ≥5 mg/day, or equivalent. Inhaled and topical steroids are allowed;
* Planned administration/administration of a vaccine not foreseen by the study protocol within the period starting 30 days before and ending 30 days after study 1st vaccination, with the exception of any licensed influenza vaccine which may be administered ≥ 15 days before/after study vaccination;
* Administration of a vaccine containing diphtheria, tetanus/pertussis antigens/diphtheria and tetanus toxoids within the previous 5 years;
* Previous experimental vaccination against RSV;

Prior/Concurrent clinical study experience • Concurrently participating in another clinical study, at any time during the study, in which the subject has been/will be exposed to an investigational/a non-investigational vaccine/product;

Other exclusions

* Pregnant/lactating female;
* Female planning to become pregnant/planning to discontinue contraceptive precautions;
* History of alcoholism, drug abuse and/or use disorder within the past 2 years;
* Any study personnel/their immediate dependents, family/household members.

Extension study

Medical conditions

* History of any reaction/hypersensitivity likely to be exacerbated by any component of the vaccines;
* Any confirmed/suspected immunosuppressive/immunodeficient condition, based on medical history and physical examination;
* Hypersensitivity to latex;
* Acute/chronic clinically significant pulmonary, cardiovascular, hepatic/renal functional abnormality;
* Significant/uncontrolled psychiatric illness;
* Recurrent history/uncontrolled neurological disorders/seizures;
* Documented HIV-positive subject;
* History of/current autoimmune disease;
* BMI\>40 kg/m\^2;
* Participants who experienced any SAE judged to be possibly or probably related to 1st dose of RSVPreF3, including hypersensitivity reactions.
* Any other clinical condition that might pose additional risk to the subject due to participation in the study.

Prior/Concomitant therapy

* Use of any investigational/non-registered product other than the study vaccines during the period starting 30 days before the 2nd vaccination, or planned use during the 6-month study extension;
* Administration of long-acting immune-modifying drugs at any time during the study;
* Administration of immunoglobulins and/or any blood products/plasma derivatives during the period starting 3 months before the 1st dose of study vaccines/planned administration during the study;
* Chronic administration of immunosuppressants or other immune-modifying drugs during the starting 3 months prior to the 1st vaccine dose(s). For corticosteroids, this will mean prednisone ≥5 mg/day, or equivalent. Inhaled and topical steroids are allowed;
* Planned administration/administration of a vaccine not foreseen by the study protocol within the period starting 30 days before and ending 30 days after study 2nd vaccination, with the exception of any licensed influenza vaccine which may be administered ≥ 15 days before/after study vaccination.

Prior/Concurrent clinical study experience

• Concurrently participating in another clinical study, at any time during the study, in which the subject has been/will be exposed to an investigational/a non-investigational vaccine/product;

Other exclusions

* Pregnant/lactating female at the time of Visit 4;
* Female planning to become pregnant/planning to discontinue contraceptive precautions;
* History of alcoholism, drug abuse and/or use disorder within the past 2 years;
* Any study personnel/their immediate dependents, family/household members.

Primary outcomes:
measure: Percentage of Subjects With Any Solicited Local Adverse Event (AEs) [Primary Study]
timeFrame: From Day 1 to Day 8
measure: Percentage of Subjects With Any Solicited General AEs [Primary Study]
timeFrame: From Day 1 to Day 8
measure: Percentage of Subjects With Any Unsolicited AEs [Primary Study]
timeFrame: From Day 1 to Day 31
measure: Number of Subjects With Any SAEs [Primary Study]
timeFrame: From Day 1 to Day 31
measure: Percentage of Subjects With Any Solicited Local AEs [Extension Study]
timeFrame: From the Day of 2nd vaccination to Day 8 post 2nd vaccination
measure: Percentage of Subjects Any Solicited General AEs [Extension Period]
timeFrame: From the Day of 2nd vaccination to Day 8 post 2nd vaccination
measure: Percentage of Subjects With Any Unsolicited AEs [Extension Period]
timeFrame: From the Day of 2nd vaccination to Day 31 post 2nd vaccination
measure: Number of Subjects With Any SAEs [Extension Period]
timeFrame: From the Day of 2nd vaccination to Day 31 post 2nd vaccination
measure: RSV A Neutralizing Antibody Geometric Mean Titers (GMTs) at Screening [Primary Study]
timeFrame: At Screening (Day -7 to Day 1)
measure: RSV A Neutralizing Antibody GMTs at Day 8 [Primary Study]
timeFrame: At Day 8
measure: RSV A Neutralizing Antibody GMTs at Day 31 [Primary Study]
timeFrame: At Day 31
measure: RSV PreF3 IgG Antibody Geometric Mean Concentration (GMCs) at Screening [Primary Study]
timeFrame: At Screening (Day -7 to Day 1)
measure: RSV PreF3 IgG GMCs at Day 8 [Primary Study]
timeFrame: At Day 8
measure: RSV PreF3 IgG GMCs at Day 31 [Primary Study]
timeFrame: At Day 31
Secondary outcomes:
measure: Percentage of Subjects With Any Solicited Local Adverse Event (AEs) by Each Boostrix Formulation [Primary Study]
timeFrame: From Day 1 to Day 8
measure: Percentage of Subjects With Any Solicited General AEs by Each Boostrix Formulation [Primary Study]
timeFrame: From Day 1 to Day 8
measure: Percentage of Subjects With Any Unsolicited AEs by Each Boostrix Formulation [Primary Study]
timeFrame: From Day 1 to Day 31
measure: Number of Subjects With Any SAEs by Each Boostrix Formulation [Primary Study]
timeFrame: From Day 1 to Day 31
measure: Number of Subjects With Any SAEs From 1st Vaccination to Day 181 [Primary Study]
timeFrame: From Day 1 to Day 181
measure: Number of Subjects With Any SAEs From 1st Vaccination to Day 181 by Each Boostrix Formulation [Primary Study]
timeFrame: From Day 1 to Day 181
measure: Number of Subjects With Any SAEs From 2nd Vaccination to Day 181 Post 2nd Vaccination [Extension Period]
timeFrame: From the Day of 2nd vaccination to Day 181 post 2nd vaccination
measure: RSV A Neutralizing GMTs at Screening by Each Boostrix Formulation [Primary Study]
timeFrame: At Screening (Day -7 to Day 1)
measure: RSV A Neutralizing GMTs at Day 8 by Each Boostrix Formulation [Primary Study]
timeFrame: At Day 8
measure: RSV A Neutralizing GMTs at Day 31 by Each Boostrix Formulation [Primary Study]
timeFrame: At Day 31
measure: RSV A Neutralizing GMTs at Single Time Point Between 12 to 18 Months Post 1st Vaccination by Each Boostrix Formulation [Primary Study]
timeFrame: At a single timepoint between 12 to 18 months post 1st vaccination
measure: RSV A Neutralizing GMTs at Single Time Point Between 12 to 18 Months Post 1st Vaccination [Primary Study]
timeFrame: At a single timepoint between 12 to 18 months post 1st vaccination
measure: RSV A Neutralizing GMTs at Day 31 Post 2nd Vaccination [Extension Study]
timeFrame: At Day 31 post 2nd vaccination
measure: RSV PreF3 IgG GMCs at Screening by Each Boostrix Formulation [Primary Study]
timeFrame: At Screening (Day -7 to Day 1)
measure: RSV PreF3 IgG GMCs at Day 8 by Each Boostrix Formulation [Primary Study]
timeFrame: At Day 8
measure: RSV PreF3 IgG GMCs at Day 31 by Each Boostrix Formulation [Primary Study]
timeFrame: At Day 31
measure: RSV PreF3 IgG GMCs at Single Time Point Between 12 to 18 Months Post 1st Vaccination by Each Boostrix Formulation [Primary Study]
timeFrame: At a single timepoint between 12 to 18 months post 1st vaccination
measure: RSV PreF3 IgG GMCs at Single Time Point Between 12 to 18 Months Post 1st Vaccination [Primary Study]
timeFrame: At a single timepoint between 12 to 18 months post 1st vaccination
measure: RSV PreF3 IgG GMCs at Day 31 Post 2nd Vaccination [Extension Study]
timeFrame: At Day 31 post 2nd vaccination
measure: Pertussis Toxoid (Anti-PT), Filamentous Hemagglutinin (Anti-FHA) and Pertactin (Anti-PRN) GMCs at Screening by Each Boostrix Formulation [Primary Study]
timeFrame: At Screening (Day -7 to Day 1)
measure: Pertussis Toxoid (Anti-PT), Filamentous Hemagglutinin (Anti-FHA) and Pertactin (Anti-PRN) GMCs at Day 31 by Each Boostrix Formulation [Primary Study]
timeFrame: At Day 31
measure: Diphtheria (Anti-D) GMC at Screening by Each Boostrix Formulation [Primary Study]
timeFrame: At Screening (Day -7 to Day 1)
measure: Diphtheria (Anti-D) GMCs at Day 31 by Each Boostrix Formulation [Primary Study]
timeFrame: At Day 31
measure: Tetanus (Anti-T) GMCs at Screening by Each Boostrix Formulation [Primary Study]
timeFrame: At Screening (Day -7 to Day 1)
measure: Tetanus (Anti-T) GMCs at Day 31 by Each Boostrix Formulation [Primary Study]
timeFrame: At Day 31
measure: Pertussis Toxoid (Anti-PT), Filamentous Hemagglutinin (Anti-FHA) and Pertactin (Anti-PRN) GMCs at Screening [Primary Study]
timeFrame: At Screening (Day -7 to Day 1)
measure: Pertussis Toxoid (Anti-PT), Filamentous Hemagglutinin (Anti-FHA) and Pertactin (Anti-PRN) GMCs at Day 31 [Primary Study]
timeFrame: At Day 31
measure: Diphtheria (Anti-D) GMCs at Screening [Primary Study]
timeFrame: At Screening (Day -7 to Day 1)
measure: Diphtheria (Anti-D) GMCs at Day 31 [Primary Study]
timeFrame: At Day 31
measure: Tetanus (Anti-T) GMCs at Screening [Primary Study]
timeFrame: At Screening (Day -7 to Day 1)
measure: Tetanus (Anti-T) GMCs at Day 31 [Primary Study]
timeFrame: At Day 31
Other outcomes:
Locations:
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Lenexa
country: United States
facility: GSK Investigational Site
state: Kansas
city: Rochester
country: United States
facility: GSK Investigational Site
state: New York
city: Seattle
country: United States
facility: GSK Investigational Site
state: Washington
city: Gent
country: Belgium
facility: GSK Investigational Site
city: Leuven
country: Belgium
facility: GSK Investigational Site
city: Truro
country: Canada
facility: GSK Investigational Site
state: Nova Scotia
city: London
country: Canada
facility: GSK Investigational Site
state: Ontario
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Hermida N, Ferguson M, Leroux-Roels I, Pagnussat S, Yaplee D, Hua N, van den Steen P, Anspach B, Dieussaert I, Kim JH. Safety and Immunogenicity of Respiratory Syncytial Virus Prefusion Maternal Vaccine Coadministered With Diphtheria-Tetanus-Pertussis Vaccine: A Phase 2 Study. J Infect Dis. 2024 Aug 16;230(2):e353-e362. doi: 10.1093/infdis/jiad560.