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

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 2

Conditions: Respiratory Syncytial Virus Infections

Treatments: Biological: RSVPreF3 formulation 3; Biological: RSVPreF3 formulation 2; Biological: Boostrix-US; Drug: Placebo; Biological: Boostrix-ex-US

Study type: Interventional

Funder types: Industry

Identifiers

NCT04138056

2019-002258-22 (EudraCT Number)

209141

Details and patient eligibility

About

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.

Enrollment: 509 patients

Sex: Female

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

509 participants in 5 patient groups, including a placebo group

RSV120_dTpa_RSV120(Pooled)

Experimental group

Description:

Subjects received one dose of 120 μg RSVPreF3 formulation 3 vaccine and either one dose of 300 μg or 500 μg dTpa (Boostrix) vaccine on Day 1 of the Primary Study and were followed up until Day 181. The subjects that agreed to participate in the Extension Study received a second dose of 120 μg RSVPreF3 formulation 3 vaccine 12 to 18 months post 1st vaccination and were followed up until the study end.

Treatment:

Biological: Boostrix-ex-US

Biological: Boostrix-US

Biological: RSVPreF3 formulation 3

RSV120_Placebo_RSV120(Pooled)

Placebo Comparator group

Description:

Subjects received one dose of 120 μg RSVPreF3 formulation 3 vaccine and one dose of Placebo on Day 1 of the Primary Study and were followed up until Day 181. The subjects that agreed to participate in the Extension Study received a second dose of 120 μg RSVPreF3 formulation 3 vaccine 12 to 18 months post 1st vaccination and were followed up until the study end.

Treatment:

Drug: Placebo

Biological: RSVPreF3 formulation 3

RSV60_dTpa_RSV120(Pooled)

Experimental group

Description:

Subjects received one dose of 60 μg RSVPreF3 formulation 2 vaccine and either one dose of 300 μg or 500 μg dTpa vaccine on Day 1 of the Primary Study and were followed up until Day 181. The subjects that agreed to participate in the Extension Study received one dose of 120 μg RSVPreF3 formulation 3 vaccine 12 to 18 months post 1st vaccination and were followed up until the study end.

Treatment:

Biological: Boostrix-ex-US

Biological: Boostrix-US

Biological: RSVPreF3 formulation 2

Biological: RSVPreF3 formulation 3

RSV60_Placebo_RSV120(Pooled)

Placebo Comparator group

Description:

Subjects received one dose of 60 μg RSVPreF3 formulation 2 vaccine and one dose of Placebo on Day 1 of the Primary Study and were followed up until Day 181. The subjects that agreed to participate in the Extension Study received one dose of 120 μg RSVPreF3 formulation 3 vaccine 12 to 18 months post 1st vaccination and were followed up until the study end.

Treatment:

Drug: Placebo

Biological: RSVPreF3 formulation 2

Biological: RSVPreF3 formulation 3

dTpa_Placebo_RSV120(Pooled)

Placebo Comparator group

Description:

Subjects received one dose of Placebo and either one dose of 300 μg or 500 μg dTpa vaccine on Day 1 of the Primary Study and were followed up until Day 181. The subjects that agreed to participate in the Extension Study received one dose of 120 μg RSVPreF3 formulation 3 vaccine 12 to 18 months post 1st vaccination and were followed up until the study end.

Treatment:

Biological: Boostrix-ex-US

Drug: Placebo

Biological: Boostrix-US

Biological: RSVPreF3 formulation 3