A Study to Evaluate Different Dose Levels of GlaxoSmithKline (GSK) Biologicals' Investigational Respiratory Syncytial Virus (RSV) Vaccine (GSK3888550A), Based on the Vaccine Safety and the Antibodies (Body Defences) Produced Following Vaccine Administration, When Given to Healthy Non-pregnant Women

NCT ID: NCT03674177

Last Updated: 2021-08-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 502 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-30
• Study Completion Date: 2019-09-02

Brief Summary

The purpose of this study is to evaluate different dose levels of the investigational RSV maternal vaccine (GSK3888550A) based on safety/reactogenicity and immune response data.

As this is the first time the investigational RSV maternal vaccine (GSK3888550A) is being been used in humans, this study will be performed in healthy non-pregnant women 18-45 years of age before testing in pregnant women.

Detailed Description

Healthy non-pregnant women 18-45 years of age will be randomized in a 1:1:1:1 ratio to receive one of three dose levels (30, 60, 120 micrograms [µg]) of the investigational RSV maternal vaccine (GSK3888550A) or placebo, administered as a single intramuscular injection (IM).

There will be a screening visit and five study visits scheduled at Day 1 (study vaccination), Day 8, Day 31, Day 61, and Day 91 to evaluate the primary and secondary objectives of safety/reactogenicity and immunogenicity profiles of the 3 dose levels. Subjects will also be contacted at Day 181. During this contact, the investigator (or delegate) will ask the subject if she has experienced any serious adverse events (SAEs) and or any adverse events (AEs) leading to study withdrawal since the last study visit (Day 360), as well as if she has become pregnant during the post-vaccination period. The investigator (or delegate) will also ask the subject about concomitant vaccinations/products/medications that she has received since the last study visit (D91). Contact should be performed preferably via telephone. Other means of contact (email/other) may be acceptable provided the required information can be fully collected.

Conditions

Respiratory Syncytial Virus Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

RSV MAT formulation 1 Group

Subjects received a single dose (30 µg) injection of the investigational RSV maternal vaccine (GSK3888550A) at Day 1, intramuscularly into the deltoid region of the non-dominant arm

Group Type: EXPERIMENTAL

GSK3888550A RSV Maternal vaccine formulation 1

Intervention Type: BIOLOGICAL

Single dose administered intramuscularly at Day 1 in the deltoid region of the non-dominant arm

RSV MAT formulation 2 Group

Subjects received a single dose (60 µg) injection of the investigational RSV maternal vaccine (GSK3888550A) at Day 1, intramuscularly into the deltoid region of the non-dominant arm

Group Type: EXPERIMENTAL

GSK3888550A RSV Maternal vaccine formulation 2

Intervention Type: BIOLOGICAL

Single dose administered intramuscularly at Day 1 in the deltoid region of the non-dominant arm

RSV MAT formulation 3 Group

Subjects received a single dose (120 µg) injection of the investigational RSV maternal vaccine (GSK3888550A) at Day 1, intramuscularly into the deltoid region of the non-dominant arm

Group Type: EXPERIMENTAL

GSK3888550A RSV Maternal vaccine formulation 3

Intervention Type: BIOLOGICAL

Single dose administered intramuscularly at Day 1 in the deltoid region of the non-dominant arm

Control Group

Subjects received a single placebo saline injection at Day 1, intramuscularly into the deltoid region of the non-dominant arm

Group Type: PLACEBO_COMPARATOR

Placebo (Normal Saline)

Intervention Type: DRUG

Single dose administered intramuscularly at Day 1 in the deltoid region of the non-dominant arm

Interventions

GSK3888550A RSV Maternal vaccine formulation 1

Single dose administered intramuscularly at Day 1 in the deltoid region of the non-dominant arm

Intervention Type: BIOLOGICAL

GSK3888550A RSV Maternal vaccine formulation 2

Single dose administered intramuscularly at Day 1 in the deltoid region of the non-dominant arm

Intervention Type: BIOLOGICAL

GSK3888550A RSV Maternal vaccine formulation 3

Single dose administered intramuscularly at Day 1 in the deltoid region of the non-dominant arm

Intervention Type: BIOLOGICAL

Placebo (Normal Saline)

Single dose administered intramuscularly at Day 1 in the deltoid region of the non-dominant arm

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Subjects who the investigator believes will comply with the requirements of the protocol (e.g. completion of the diary cards/questionnaires, return for follow-up visits, have regular contact to allow evaluation during the study);
• Written informed consent obtained from the subject;
• Healthy female subjects; as established by medical history and clinical examination, aged 18 to 45 years at the time of the vaccination;
• Female subjects of childbearing potential may be enrolled in the study, if the subject:

• has practiced adequate contraception for 30 days prior to vaccination, and
• has a negative pregnancy test on the day of vaccination, and has agreed to continue adequate contraception until 90 days after vaccination

Exclusion Criteria

• Use of any investigational or non-registered product other than the study vaccine within 30 days preceding vaccination or any planned use during the study period;
• Concurrently participating in the active phase of 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
• Chronic administration (defined as more than 14 days in total) of immunosuppressant or other immune-modifying drugs, as well as administration of long acting immune modifying drugs, within 6 months prior to the vaccine dose (for corticosteroids, this will mean prednisone higher than or equal to (≥) 5 milligrams per day (mg/day), or equivalent). Inhaled and topical steroids are allowed;
• Administration of immunoglobulins and/or any blood products during the period starting 3 months before the study vaccination, or planned administration until 90 days post-vaccination;
• 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 vaccination, with the exception of any licensed influenza vaccine which may be administered ≥ 15 days before or after study vaccination;
• Previous experimental vaccination against RSV;
• Presence of neurological or psychiatric diagnoses which, although stable, are deemed by the investigator to render the potential subject unable/unlikely to provide accurate safety reports;
• Family history of congenital or hereditary immunodeficiency;
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination;
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine;
• Any acute or chronic, clinically significant disease, as determined by physical examination, laboratory screening tests, subject personal report and/or health care provider information. The following conditions will be exclusionary:

• Diabetes mellitus,
• Respiratory diseases, such as:

• Chronic Pulmonary diseases, including Chronic Obstructive Pulmonary Disease (COPD),
• Bronchopulmonary dysplasia (note: history of past bronchopulmonary dysplasia as a neonate/infant will not be exclusionary),
• Uncontrolled asthma or asthma necessitating treatment with chronic systemic glucocorticoids
• Significant and/or uncontrolled psychiatric illness:

• hospitalization for psychiatric illness, history of suicide attempt(s) or confinement for danger to self or others within 10 years
• clinically significant depression
• Major neurological disease including:

• seizure or adulthood epilepsy (note: history of febrile convulsion in childhood is not exclusionary)
• myasthenia gravis
• history of repetitive migraine mal/status migrainosus
• Significant cardiovascular disease, including:

• Uncontrolled arterial hypertension,
• Congenital heart disease (with the exception of corrected atrial or ventricular septal defects),
• Previous myocardial infarction,
• Valvular heart disease or history of rheumatic fever,
• Previous bacterial endocarditis,
• History of cardiac surgery (with the exception of corrected atrial or ventricular septal defects),
• Personal or family history of cardiomyopathy or sudden adult death.
• Known or suspected Hepatitis B or Hepatitis C infection,
• Any other significant uncontrolled medical illness, defined as any illness requiring new medical and/or surgical treatment or significant modification of treatment dose due to uncontrolled symptoms or drug toxicity, within 3 months prior to study vaccination.
• History of or current autoimmune disease;
• Body mass index (BMI) > 40 Kilograms (kg)/square meters(m^2);
• Pregnant or lactating female;
• Female planning to become pregnant or planning to discontinue contraceptive precautions;
• Hypersensitivity to latex;
• Lymphoproliferative disorder or malignancy within previous 5 years;
• Acute disease and/or fever at the time of enrolment;

• Fever is defined as temperature ≥ 38°C/100.4°F
• For subjects with acute disease and/or fever at the time of enrolment, Visit 1 will be rescheduled within the allowed window for the visit.
• Subjects with fever at screening may be re-screened 1 time at a later date.
• Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may be enrolled at the discretion of the investigator.
• Any clinically significant or any ≥ Grade 2* haematological (haemoglobin level, white blood cell, lymphocyte, neutrophil, eosinophil, and platelets) and biochemical (alanine aminotransferase [ALT] aspartate aminotransferase [AST], creatinine, blood urea nitrogen [BUN]) laboratory abnormality detected at the last screening blood sampling; *Grading of laboratory parameters will be based on the FDA Guidance for Industry "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials".

For Grade 1 laboratory abnormalities, the investigator should use clinical judgement to decide which ones are clinically relevant.

Subjects with haematological/biochemical values out of normal range at screening which are expected to be temporary, may be re-screened 1 time at a later date.

• Any other condition that the investigator judges may interfere with study procedures or findings;
• Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe;
• Alcoholism, drug abuse and/or use disorder within the past two years (as defined in Diagnostic and Statistical Manual of Mental Disorders [DSM-5] Diagnostic Criteria);
• Planned move to a location that will prohibit participating in the trial until study end.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Lenexa, Kansas, United States

GSK Investigational Site

Rochester, New York, United States

GSK Investigational Site

Helsinki, , Finland

GSK Investigational Site

Tampere, , Finland

GSK Investigational Site

Turku, , Finland

GSK Investigational Site

Turku, , Finland

GSK Investigational Site

Würzburg, Bavaria, Germany

GSK Investigational Site

Hanover, Lower Saxony, Germany

GSK Investigational Site

Goch, North Rhine-Westphalia, Germany

GSK Investigational Site

Mainz, Rhineland-Palatinate, Germany

GSK Investigational Site

Hamburg, , Germany

Countries

United States; Finland; Germany

References

Schwarz TF, Johnson C, Grigat C, Apter D, Csonka P, Lindblad N, Nguyen TL, Gao FF, Qian H, Tullio AN, Dieussaert I, Picciolato M, Henry O. Three Dose Levels of a Maternal Respiratory Syncytial Virus Vaccine Candidate Are Well Tolerated and Immunogenic in a Randomized Trial in Nonpregnant Women. J Infect Dis. 2022 Jun 15;225(12):2067-2076. doi: 10.1093/infdis/jiab317.

Reference Type: BACKGROUND

PMID: 34146100 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2018-001340-62

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

208068

Identifier Type: -

Identifier Source: org_study_id