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

• ClinicalTrials.gov Identifier: NCT03674177
• Recruitment Status: Completed
• First Posted: September 17, 2018
• Results First Posted: April 15, 2020
• Last Update Posted: December 7, 2020
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Respiratory Syncytial Virus Infections	Biological: GSK3888550A RSV Maternal vaccine formulation 1; Biological: GSK3888550A RSV Maternal vaccine formulation 2; Biological: GSK3888550A RSV Maternal vaccine formulation 3; Drug: Placebo (Normal Saline)	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 502 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Masking Description: Observer-blind In this study, the subject and study site personnel involved in the clinical evaluations of the subjects are blinded while other study personnel may be aware of the treatment assignments.
• Primary Purpose: Prevention
• Official Title: A Study to Evaluate the Safety, Reactogenicity and Immunogenicity of GSK Biologicals' Investigational Unadjuvanted RSV Maternal Vaccine Compared to Placebo When Administered to Healthy Non-pregnant Women.
• Actual Study Start Date: October 30, 2018
• Actual Primary Completion Date: April 16, 2019
• Actual Study Completion Date: September 2, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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	Biological: GSK3888550A RSV Maternal vaccine formulation 1; Single dose administered intramuscularly at Day 1 in the deltoid region of the non-dominant arm
Experimental: 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	Biological: GSK3888550A RSV Maternal vaccine formulation 2; Single dose administered intramuscularly at Day 1 in the deltoid region of the non-dominant arm
Experimental: 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	Biological: GSK3888550A RSV Maternal vaccine formulation 3; Single dose administered intramuscularly at Day 1 in the deltoid region of the non-dominant arm
Placebo Comparator: Control Group; Subjects received a single placebo saline injection at Day 1, intramuscularly into the deltoid region of the non-dominant arm	Drug: Placebo (Normal Saline); Single dose administered intramuscularly at Day 1 in the deltoid region of the non-dominant arm

Outcome Measures

Primary Outcome Measures :

1. Number of Subjects With Any and Grade 3 Solicited Local Adverse Events (AE) During a 7-day Follow-up Period [ Time Frame: During a 7-day follow-up period (i.e., on the day of vaccination and 6 subsequent days) ]

   Assessed solicited local symptoms include pain, redness and swelling, at the injection site. Any = occurrence of the AE regardless of intensity grade. Any Redness and swelling symptom = symptom reported with a surface diameter greater than 20 millimeters.

   Grade 3 pain = significant pain at rest, pain that prevented normal every day activity. Grade 3 redness/swelling = symptom reported with a surface diameter greater than 100 millimeters.

2. Number of Subjects With Any, Grade 3 and Related Solicited General Adverse Events (AE) During a 7-day Follow-up Period [ Time Frame: During a 7-day follow-up period (i.e., on the day of vaccination and 6 subsequent days) ]

   Assessed solicited general symptoms include fatigue, gastrointestinal symptoms (nausea, vomiting, diarrhea and/or abdominal pain), headache and fever.

   Any Fatigue, gastrointestinal symptoms and headache = occurrence of the symptom regardless of intensity grade and relationship. Any Fever = temperature higher than or equal to 38.0 degrees Celsius (°C), or 100.4 degrees Fahrenheit (°F).

   Grade 3 Fatigue, gastrointestinal symptoms and headache = symptoms that prevented normal activities. Grade 3 Fever = temperature higher than 39.0 degrees Celsius (°C), or 102.2 degrees Fahrenheit (°F).

   Related fatigue, gastrointestinal symptoms, headache and fever(>38°C) = symptoms assessed by the investigator as related to the vaccination.

3. Number of Subjects With Any Unsolicited AEs During a 30-day Follow-up Period [ Time Frame: During a 30-day follow-up period after vaccination (i.e., on the day of vaccination and 29 subsequent days) ]
   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 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.
4. Number of Subjects With Serious Adverse Events (SAEs) During a 30-day Follow-up Period [ Time Frame: From Day 1 (vaccination) up to Day 30 (i.e., on the day of vaccination and 29 subsequent days) ]
   Assessed SAEs include any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, or results in disability/incapacity, or is a congenital anomaly/birth defect in the offspring of a study subject.
5. Number of Subjects With Hematological Laboratory Results Change With Respect to Normal Laboratory Ranges and Versus Baseline, at Day 8 [ Time Frame: At Day 8 ]
   Assessed hematological laboratory parameters include Eosinophils, Hemoglobin, Lymphocytes, Neutrophils, Platelets, White blood cells (WBC). Hematological abnormalities refer to range indicator at timing, categorized as BELOW, WITHIN or ABOVE normal ranges, and compared to baseline range indicator i.e. BELOW(SCR), WITHIN(SCR) or ABOVE(SCR). [e.g. WBC, BELOW(SCR), BELOW = WBC BELOW normal ranges at baseline versus BELOW normal ranges at Day 8].
6. Number of Subjects With Hematological Laboratory Results Change With Respect to Normal Laboratory Ranges and Versus Baseline, at Day 31 [ Time Frame: At Day 31 ]
   Assessed hematological laboratory parameters include Eosinophils, Hemoglobin, Lymphocytes, Neutrophils, Platelets, White blood cells (WBC). Hematological abnormalities refer to range indicator at timing, categorized as BELOW, WITHIN or ABOVE normal ranges, and compared to baseline range indicator i.e. BELOW(SCR), WITHIN(SCR) or ABOVE(SCR) [e.g. WBC, BELOW(SCR), BELOW = WBC BELOW normal ranges at baseline versus BELOW normal ranges at Day 31].
7. Number of Subjects With Biochemical Laboratory Results Change With Respect to Normal Laboratory Ranges and Versus Baseline, at Day 8 [ Time Frame: At Day 8 ]
   Assessed biochemical laboratory parameters include alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN) and creatinine. Biochemical abnormalities refer to range indicator at timing, categorized as BELOW, WITHIN or ABOVE normal ranges, and compared to baseline range indicator i.e. BELOW(SCR), WITHIN(SCR) or ABOVE(SCR)[e.g. ALT, BELOW(SCR), BELOW = ALT BELOW normal ranges at baseline versus BELOW normal ranges at Day 8].
8. Number of Subjects With Biochemical Laboratory Results Change With Respect to Normal Laboratory Ranges and Versus Baseline, at Day 31 [ Time Frame: At Day 31 ]
   Assessed biochemical laboratory parameters include alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine and blood urea nitrogen (BUN). Biochemical abnormalities refer to range indicator at timing, categorized as BELOW, WITHIN or ABOVE normal ranges, and compared to baseline range indicator i.e. BELOW(SCR), WITHIN(SCR) or ABOVE(SCR) [e.g. ALT, BELOW(SCR), BELOW = ALT BELOW normal ranges at baseline versus BELOW normal ranges at Day 31].
9. Number of Subjects With Hematological Laboratory Results Versus Baseline, by Maximum Grading, at Day 8 [ Time Frame: At Day 8 ]
   Assessed hematological laboratory parameters include Eosinophils, Hemoglobin, Lymphocytes Decrease, Neutrophils Decrease, Platelets Decrease, WBC Decrease and WBC Increase, as graded by the Food and Drug Administration [FDA] Guidance for Industry "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. Assessed grades at specified time point, are Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe and Grade 4 = life threatening, as compared to the baseline status of the same parameter, at baseline [e.g. WBC decrease-Grade 1(SCR)-Grade 1 = WBC decrease Grade 1 at baseline versus Grade 1 at Day 8]. "Any" corresponding to any grade and "Grade 0" to normal ranges.
10. Number of Subjects With Hematological Laboratory Results Versus Baseline, by Maximum Grading, at Day 31 [ Time Frame: At Day 31 ]
    Assessed hematological laboratory parameters include Eosinophils, Hemoglobin, Lymphocytes Decrease, Neutrophils Decrease, Platelets Decrease, WBC Decrease and WBC Increase, as graded by the Food and Drug Administration [FDA] Guidance for Industry "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. Assessed grades at specified time point, are Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe and Grade 4 = life threatening, as compared to the baseline status of the same parameter, at baseline [e.g. WBC decrease-Grade 1(SCR)-Grade 1 = WBC decrease Grade 1 at baseline versus Grade 1 at Day 31]. "Any" corresponding to any grade and "Grade 0" to normal ranges.
11. Number of Subjects With Biochemical Laboratory Results Versus Baseline, by Maximum Grading, at Day 8 [ Time Frame: At Day 8 ]
    Assessed biochemical laboratory parameters include alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN) and creatinine, as graded by the Food and Drug Administration [FDA] Guidance for Industry "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. Assessed grades at specified time point, are Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe and Grade 4 = life threatening, as compared to the baseline status of the same parameter, at baseline [e.g. ALT-Grade 1(SCR)-Grade 1 = ALT Grade 1 at baseline versus Grade 1 at Day 8]. "Any" corresponding to any grade and "Grade 0" to normal ranges.
12. Number of Subjects With Biochemical Laboratory Results Versus Baseline, by Maximum Grading, at Day 31 [ Time Frame: At Day 31 ]
    Assessed biochemical laboratory parameters include alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN) and creatinine, as graded by the Food and Drug Administration [FDA] Guidance for Industry "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. Assessed grades at specified time point, are Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe and Grade 4 = life threatening, as compared to the baseline status of the same parameter, at baseline [e.g. ALT-Grade 1(SCR)-Grade 1 = ALT Grade 1 at baseline versus Grade 1 at Day 31]. "Any" corresponding to any grade and "Grade 0" to normal ranges.

Secondary Outcome Measures :

1. Number of Subjects With SAEs [ Time Frame: From Day 1 (vaccination) up to Day 91 and up to Day 181 ]
   Assessed SAEs include any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, or results in disability/incapacity, or is a congenital anomaly/birth defect in the offspring of a study subject.
2. Neutralizing Antibody (Nab) Titers Against RSV Serotype A [ Time Frame: At pre-vaccination at screening (PRE), 7 days post vaccination (Day 8), 30 days post vaccination (Day 31), 60 days post vaccination (Day 61) and 90 days post vaccination (Day 91) ]
   Anti RSV-A neutralizing antibody titers are given as geometric mean titers (GMTs) and expressed as Estimated Dose: serum dilution giving a 60% reduction of the signal compared to a control without serum (ED60), calculated on subjects with anti-RSV-A neutralizing antibody titer equal to or above the assay cut-off 18 ED60.
3. Anti-RSVPreF3 Immunoglobulin G (IgG) Antibody Concentrations [ Time Frame: At pre-vaccination at screening (PRE), 7 days post vaccination (Day 8), 30 days post vaccination (Day 31), 60 days post vaccination (Day 61) and 90 days post vaccination (Day 91) ]
   Concentrations are presented as geometric mean concentrations (GMCs), expressed in Enzyme Linked Immunosorbent Assay (ELISA) units per millilitre (EL.U/mL), calculated on subjects with anti-RSVPreF3 antibody concentration equal to or above the assay cut-off 25 EL.U/mL.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: The vaccine is for use in pregnant women, as such, the study is female only.
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

United States, Kansas

GSK Investigational Site

Lenexa, Kansas, United States, 66219

United States, New York

GSK Investigational Site

Rochester, New York, United States, 14609

Finland

GSK Investigational Site

Helsinki, Finland, 00260

GSK Investigational Site

Tampere, Finland, FI-33100

GSK Investigational Site

Turku, Finland, 20100

GSK Investigational Site

Turku, Finland, 20540

Germany

GSK Investigational Site

Wuerzburg, Bayern, Germany, 97070

GSK Investigational Site

Hannover, Niedersachsen, Germany, 30159

GSK Investigational Site

Goch, Nordrhein-Westfalen, Germany, 47574

GSK Investigational Site

Mainz, Rheinland-Pfalz, Germany, 55116

GSK Investigational Site

Hamburg, Germany, 22143

Sponsors and Collaborators

GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

  Study Documents (Full-Text)

Documents provided by GlaxoSmithKline:

Study Protocol  [PDF] August 13, 2018

Statistical Analysis Plan  [PDF] October 25, 2018

More Information

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT03674177
• Other Study ID Numbers: 208068; 2018-001340-62 ( EudraCT Number )
• First Posted: September 17, 2018
• Results First Posted: April 15, 2020
• Last Update Posted: December 7, 2020
• Last Verified: November 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (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.
• URL: https://clinicalstudydatarequest.com

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by GlaxoSmithKline:

Vaccines; Safety; Immunogenicity; Reactogenicity; Respiratory Syncytial Viruses

Additional relevant MeSH terms:

Respiratory Syncytial Virus Infections; Virus Diseases; Pneumovirus Infections; Paramyxoviridae Infections; Mononegavirales Infections; RNA Virus Infections; Vaccines; Immunologic Factors; Physiological Effects of Drugs