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

NCT03674177 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 2080682018-001340-62
• Study Type: interventional
• Target: 502
• Locations: 3 countries
• Sites: 11

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.

Conditions

Respiratory Syncytial Virus Infections

Keywords

Vaccines; Safety; Immunogenicity; Reactogenicity; Respiratory Syncytial Viruses

Outcome Measures

Primary Outcomes (12)

• Number of Subjects With Any and Grade 3 Solicited Local Adverse Events (AE) During a 7-day Follow-up Period

  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.

  During a 7-day follow-up period (i.e., on the day of vaccination and 6 subsequent days)

• Number of Subjects With Any, Grade 3 and Related Solicited General Adverse Events (AE) During a 7-day Follow-up Period

  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.

  During a 7-day follow-up period (i.e., on the day of vaccination and 6 subsequent days)

• Number of Subjects With Any Unsolicited AEs During a 30-day Follow-up Period

  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.

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

• Number of Subjects With Serious Adverse Events (SAEs) During a 30-day Follow-up Period

  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.

  From Day 1 (vaccination) up to Day 30 (i.e., on the day of vaccination and 29 subsequent days)

• Number of Subjects With Hematological Laboratory Results Change With Respect to Normal Laboratory Ranges and Versus Baseline, 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). \[e.g. WBC, BELOW(SCR), BELOW = WBC BELOW normal ranges at baseline versus BELOW normal ranges at Day 8\].

  At Day 8

• Number of Subjects With Hematological Laboratory Results Change With Respect to Normal Laboratory Ranges and Versus Baseline, 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) \[e.g. WBC, BELOW(SCR), BELOW = WBC BELOW normal ranges at baseline versus BELOW normal ranges at Day 31\].

  At Day 31

• Number of Subjects With Biochemical Laboratory Results Change With Respect to Normal Laboratory Ranges and Versus Baseline, 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)\[e.g. ALT, BELOW(SCR), BELOW = ALT BELOW normal ranges at baseline versus BELOW normal ranges at Day 8\].

  At Day 8

• Number of Subjects With Biochemical Laboratory Results Change With Respect to Normal Laboratory Ranges and Versus Baseline, 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) \[e.g. ALT, BELOW(SCR), BELOW = ALT BELOW normal ranges at baseline versus BELOW normal ranges at Day 31\].

  At Day 31

• Number of Subjects With Hematological Laboratory Results Versus Baseline, by Maximum Grading, 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.

  At Day 8

• Number of Subjects With Hematological Laboratory Results Versus Baseline, by Maximum Grading, 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.

  At Day 31

• Number of Subjects With Biochemical Laboratory Results Versus Baseline, by Maximum Grading, 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.

  At Day 8

• Number of Subjects With Biochemical Laboratory Results Versus Baseline, by Maximum Grading, 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.

  At Day 31

Secondary Outcomes (3)

• Number of Subjects With SAEs

  From Day 1 (vaccination) up to Day 91 and up to Day 181

• Neutralizing Antibody (Nab) Titers Against RSV Serotype A

  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-RSVPreF3 Immunoglobulin G (IgG) Antibody Concentrations

  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)

Study Arms (4)

RSV MAT formulation 1 Group

EXPERIMENTAL

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

RSV MAT formulation 2 Group

EXPERIMENTAL

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

RSV MAT formulation 3 Group

EXPERIMENTAL

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

Control Group

PLACEBO COMPARATOR

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

Drug: Placebo (Normal Saline)

Interventions

GSK3888550A RSV Maternal vaccine formulation 1 BIOLOGICAL

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

RSV MAT formulation 1 Group

GSK3888550A RSV Maternal vaccine formulation 2 BIOLOGICAL

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

RSV MAT formulation 2 Group

GSK3888550A RSV Maternal vaccine formulation 3 BIOLOGICAL

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

RSV MAT formulation 3 Group

Placebo (Normal Saline) DRUG

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

Control Group

Eligibility Criteria

• Age: 18 Years - 45 Years
• Gender Eligibility Details: The vaccine is for use in pregnant women, as such, the study is female only.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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;
• Diabetes mellitus,
• Respiratory diseases, such as:
• Chronic Pulmonary diseases, including Chronic Obstructive Pulmonary Disease (COPD),
• Uncontrolled asthma or asthma necessitating treatment with chronic systemic glucocorticoids
• Significant and/or uncontrolled psychiatric illness:

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (11)

GSK Investigational Site

Lenexa, Kansas, 66219, United States

Location

GSK Investigational Site

Rochester, New York, 14609, United States

Location

GSK Investigational Site

Helsinki, 00260, Finland

Location

GSK Investigational Site

Tampere, FI-33100, Finland

Location

GSK Investigational Site

Turku, 20100, Finland

Location

GSK Investigational Site

Turku, 20540, Finland

Location

GSK Investigational Site

Würzburg, Bavaria, 97070, Germany

Location

GSK Investigational Site

Hanover, Lower Saxony, 30159, Germany

Location

GSK Investigational Site

Goch, North Rhine-Westphalia, 47574, Germany

Location

GSK Investigational Site

Mainz, Rhineland-Palatinate, 55116, Germany

Location

GSK Investigational Site

Hamburg, 22143, Germany

Location

Related Publications (1)

• 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.

  PMID: 34146100 BACKGROUND

MeSH Terms

Conditions

Respiratory Syncytial Virus Infections

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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
• Masking Details: 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.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2018
• First Posted: September 17, 2018
• Study Start: October 30, 2018
• Primary Completion: April 16, 2019
• Study Completion: September 2, 2019
• Last Updated: August 13, 2021
• Results First Posted: April 15, 2020

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (copy the URL below to your browser)
• 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

DE (5); US (2); FI (4)