A Phase III Study to Assess the Lot-to-lot Consistency of GSK's Investigational RSV Maternal Vaccine and the Immune Response and Safety of RSV Maternal Vaccine When Given Alone or Co-administered With GSK's Influenza D-QIV Vaccine in Healthy Non-pregnant Women.

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Completed

CT.gov ID

NCT05045144

Collaborator

(none)

1,589

Enrollment

Locations

Arms

8.7

Actual Duration (Months)

44.1

Patients Per Site

5.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the clinical lot-to-lot consistency of the respiratory syncytial virus (RSV) maternal (RSV MAT) vaccine administered to healthy non-pregnant women 18-49 years of age (YOA). In addition, this study will evaluate immunogenicity, safety and reactogenicity from co-administration of RSV MAT vaccine and GSK's quadrivalent seasonal influenza (Flu D-QIV) vaccine.

Condition or Disease	Intervention/Treatment	Phase
Respiratory Syncytial Virus Infections	Combination Product: RSV MAT Lot 1 vaccine (GSK3888550A) Combination Product: RSV MAT Lot 2 vaccine (GSK3888550A) Combination Product: RSV MAT Lot 3 vaccine (GSK3888550A) Combination Product: Flu D-QIV vaccine Combination Product: Placebo	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

1589 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Observer-blind (lot-to-lot consistency) & single-blind (immunogenicity, safety and reactogenicity)

Primary Purpose:

Prevention

Official Title:

A Phase III, Randomized, Multi-country Study to Evaluate the Lot-to-lot Consistency of GSK's Investigational RSV Maternal Vaccine and the Immune Response, Safety and Reactogenicity of RSV Maternal Vaccine When Co-administered With GSK's Quadrivalent Influenza D-QIV Vaccine in Healthy Non-pregnant Women 18-49 Years of Age.

Actual Study Start Date :

Sep 15, 2021

Actual Primary Completion Date :

Jan 28, 2022

Actual Study Completion Date :

Jun 6, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: RSV1 Group Participants randomized to the RSV1 Group receive one dose of RSV MAT Lot 1 vaccine intramuscularly at Day 1. Participants are also provided with an option of receiving Flu D-QIV vaccine at Day 31 to allow the participants receive the standard of care.	Combination Product: RSV MAT Lot 1 vaccine (GSK3888550A) One dose of RSV MAT Lot 1 vaccine (GSK3888550A), administered intramuscularly in the deltoid region of the left arm, at Day 1.
Experimental: RSV2 Group Participants randomized to the RSV2 Group receive one dose of RSV MAT Lot 2 vaccine intramuscularly at Day 1. Participants are also provided with an option of receiving Flu D-QIV vaccine at Day 31 to allow the participants receive the standard of care.	Combination Product: RSV MAT Lot 2 vaccine (GSK3888550A) One dose of RSV MAT Lot 2 vaccine (GSK3888550A), administered intramuscularly in the deltoid region of the left arm, at Day 1.
Experimental: RSV3 Group Participants randomized to the RSV3 Group receive one dose of RSV MAT Lot 3 vaccine intramuscularly at Day 1. Participants are also provided with an option of receiving Flu D-QIV vaccine at Day 31 to allow the participants receive the standard of care.	Combination Product: RSV MAT Lot 3 vaccine (GSK3888550A) One dose of RSV MAT Lot 3 vaccine (GSK3888550A), administered intramuscularly in the deltoid region of the left arm, at Day 1.
Experimental: RSV1+Flu Group Participants randomized to the RSV1+Flu Group receive one dose of RSV MAT Lot 1 vaccine co-administered with one dose of Flu D-QIV vaccine, intramuscularly, at Day 1.	Combination Product: RSV MAT Lot 1 vaccine (GSK3888550A) One dose of RSV MAT Lot 1 vaccine (GSK3888550A), administered intramuscularly in the deltoid region of the left arm, at Day 1. Combination Product: Flu D-QIV vaccine One dose of Flu D-QIV vaccine administered intramuscularly: - in the deltoid region of the right arm, at Day 1 for the RSV1+Flu, RSV2+Flu and RSV3+Flu groups. - in the deltoid region of the left arm, at Day 1 for the Flu+P group. - in the deltoid region of the non-dominant arm, at Day 31 for the RSV1, RSV2 and RSV3 groups, as an optional vaccination for participants to provide standard of care.
Experimental: RSV2+Flu Group Participants randomized to the RSV2+Flu Group receive one dose of RSV MAT Lot 2 vaccine co-administered with one dose of Flu D-QIV vaccine, intramuscularly, at Day 1.	Combination Product: RSV MAT Lot 2 vaccine (GSK3888550A) One dose of RSV MAT Lot 2 vaccine (GSK3888550A), administered intramuscularly in the deltoid region of the left arm, at Day 1. Combination Product: Flu D-QIV vaccine One dose of Flu D-QIV vaccine administered intramuscularly: - in the deltoid region of the right arm, at Day 1 for the RSV1+Flu, RSV2+Flu and RSV3+Flu groups. - in the deltoid region of the left arm, at Day 1 for the Flu+P group. - in the deltoid region of the non-dominant arm, at Day 31 for the RSV1, RSV2 and RSV3 groups, as an optional vaccination for participants to provide standard of care.
Experimental: RSV3+Flu Group Participants randomized to the RSV3+Flu Group receive one dose of RSV MAT Lot 3 vaccine co-administered with one dose of Flu D-QIV vaccine, intramuscularly, at Day 1.	Combination Product: RSV MAT Lot 3 vaccine (GSK3888550A) One dose of RSV MAT Lot 3 vaccine (GSK3888550A), administered intramuscularly in the deltoid region of the left arm, at Day 1. Combination Product: Flu D-QIV vaccine One dose of Flu D-QIV vaccine administered intramuscularly: - in the deltoid region of the right arm, at Day 1 for the RSV1+Flu, RSV2+Flu and RSV3+Flu groups. - in the deltoid region of the left arm, at Day 1 for the Flu+P group. - in the deltoid region of the non-dominant arm, at Day 31 for the RSV1, RSV2 and RSV3 groups, as an optional vaccination for participants to provide standard of care.
Active Comparator: Flu+P Group Participants randomized to the Flu+P Group receive one dose of Flu D-QIV vaccine co-administered with one dose of Placebo, intramuscularly, at Day 1.	Combination Product: Flu D-QIV vaccine One dose of Flu D-QIV vaccine administered intramuscularly: - in the deltoid region of the right arm, at Day 1 for the RSV1+Flu, RSV2+Flu and RSV3+Flu groups. - in the deltoid region of the left arm, at Day 1 for the Flu+P group. - in the deltoid region of the non-dominant arm, at Day 31 for the RSV1, RSV2 and RSV3 groups, as an optional vaccination for participants to provide standard of care. Combination Product: Placebo One dose of placebo, administered intramuscularly in the deltoid region of the right arm, at Day 1.

Outcome Measures

Primary Outcome Measures

Percentage of participants reporting solicited administration site events in all study groups [From Day 1 to Day 7 included]
Assessed solicited administration site events include pain, redness and swelling.
Percentage of participants reporting solicited systemic events in all study groups [From Day 1 to Day 7 included]
Assessed solicited systemic events include fever, headache, gastrointestinal (GI) symptoms (nausea, vomiting, diarrhea, abdominal pain) and fatigue. The preferred location for measuring temperature is the oral cavity. Fever is defined as temperature equal to or above (≥) 38.0 °C/ 100.4°F.
Percentage of participants reporting unsolicited adverse events (AEs) in all study groups [From Day 1 to Day 30 included]
Any AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is reported as an unsolicited adverse event.
Percentage of participants reporting serious adverse events (SAEs) in all study groups [From Day 1 to Day 30 included]
An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant or results in abnormal pregnancy outcomes.
Percentage of participants reporting SAEs in all study groups [From first vaccination up to study end (Day 1 to Day 181)]
An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant or results in abnormal pregnancy outcomes.
RSV MAT immunoglobulin G (IgG) concentrations for participants in RSV1, RSV2 and RSV3 groups at Day 31 [At Day 31]
Serological assays for the determination of IgG antibodies against RSV MAT are performed by Enzyme-Linked Immunosorbent Assay (ELISA). RSV MAT IgG concentrations are expressed as geometric mean concentrations (GMCs), in ELISA units per milliliter (ELU/mL).
Flu D-QIV haemagglutinin inhibition (HI) antibody titers against 3 influenza strains for participants in Flu+P group and RSV+Flu pooled group at Day 31 [At Day 31]
Flu D-QIV HI antibody titers against 3 influenza strains (A/Tasmania/503/2020 (H3N2) IVR-221; B/Washington/02/2019; B/Phuket/3073/2013) are expressed as geometric mean titers (GMTs), as assessed by HI assay. RSV+Flu pooled group consists of participants pooled from RSV1+Flu, RSV2+Flu and RSV3+Flu groups.

Secondary Outcome Measures

RSV A neutralizing antibody titers for participants in RSV+Flu pooled group and RSV pooled group at Day 1 and Day 31 [At Day 1 and Day 31]
Serological assays for the determination of antibodies against RSV A are performed by neutralization assay. RSV A neutralizing antibody titers are expressed as geometric mean titers (GMTs). The RSV+Flu pooled group consists of participants pooled from RSV1+Flu, RSV2+Flu and RSV3+Flu groups. The RSV pooled group consists of participants pooled from RSV1, RSV2 and RSV3 groups.
Seroconversion rate (SCR) to Flu D-QIV HI antibody titers against 3 influenza strains for participants in Flu+P group and RSV+Flu pooled group at Day 31 [At Day 31]
The SCR is defined as the proportion of participants with: A Day 1 (pre-vaccination) serum anti-HI titer <1:10 and a Day 31 (post-vaccination) serum anti-HI titer ≥1:40, or. A Day 1 (pre-vaccination) serum anti-HI titer ≥ 1:10 and a fold increase (post/pre) ≥ 4 at Day 31. The 3 influenza strains assessed are: A/Tasmania/503/2020 (H3N2) IVR-221; B/Washington/02/2019; B/Phuket/3073/2013. The RSV+Flu pooled group consists of participants pooled from RSV1+Flu, RSV2+Flu and RSV3+Flu groups.
RSV B neutralizing antibody titers for participants in RSV+Flu pooled group and RSV pooled group at Day 1 and Day 31 [At Day 1 and Day 31]
Serological assays for the determination of antibodies against RSV B are performed by neutralization assay. RSV B neutralizing antibody titers are expressed as GMTs. The RSV+Flu pooled Group consists of participants pooled from RSV1+Flu, RSV2+Flu and RSV3+Flu groups. The RSV pooled Group consists of participants pooled from RSV1, RSV2 and RSV3 groups.
RSV MAT IgG concentrations for participants in RSV+Flu pooled group and RSV pooled group at Day 1 and Day 31 [At Day 1 and Day 31]
Serological assays for the determination of IgG antibodies against RSV MAT are performed by ELISA. RSV MAT IgG concentrations are expressed as GMCs, in ELU/mL.
Flu D-QIV HI antibody titers against 3 influenza strains for participants in Flu+P group and RSV+Flu pooled group at Day 1 and Day 31 [At Day 1 and Day 31]
Flu D-QIV HI antibody titers against 3 influenza strains (A/Tasmania/503/2020 (H3N2) IVR-221; B/Washington/02/2019; B/Phuket/3073/2013) are expressed as geometric mean titers (GMTs), as assessed by HI assay.
Seroprotection rate (SPR) to Flu D-QIV HI antibody titers for participants in Flu+P group and RSV+Flu pooled group at Day 1 and Day 31 [At Day 1 and Day 31]
SPR is measured by the proportion of participants achieving an HI antibody titer ≥1:40.
RSV A neutralizing antibody titers for participants in RSV1, RSV2 and RSV 3 groups at Day 1 and Day 31 [At Day 1 and Day 31]
Serological assays for the determination of antibodies against RSV-A are performed by neutralization assay. RSV A neutralizing antibody titers are expressed as GMTs.
RSV B neutralizing antibody titers for participants in RSV1, RSV2 and RSV 3 groups at Day 1 and Day 31 [At Day 1 and Day 31]
Serological assays for the determination of antibodies against RSV B are performed by neutralization assay. RSV B neutralizing antibody titers are expressed as GMTs.
RSV MAT IgG concentrations for participants in RSV1, RSV2 and RSV3 groups at Day 1 and Day 31 [At Day 1 and Day 31]
Serological assays for the determination of IgG antibodies against RSV MAT are performed by ELISA. RSV MAT IgG concentrations are expressed as GMCs, in ELU/mL.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 49 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Participants 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 participant prior to performance of any study specific procedure.
Healthy female participants; as established by medical history and clinical examination, aged 18 to 49 years at the time of the first study intervention administration.
Female participants of childbearing potential may be enrolled in the study, if the participant:
has practiced adequate contraception for 1 month prior to study intervention administration, and
has a negative pregnancy test on the day of study intervention administration, and
has agreed to continue adequate contraception during the entire treatment period and for 1 month after completion of the study intervention administration.
No local condition precluding injection in both left and right deltoid muscles.

Exclusion Criteria:

Medical conditions

History of any reaction or hypersensitivity likely to be exacerbated by any component of the study interventions;
Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination;
Current autoimmune disorder, for which the participant has received immune-modifying therapy within 6 months, before study vaccination;
Hypersensitivity to latex;
Acute or chronic clinically significant abnormality or poorly controlled pre-existent co-morbidities or any other clinical conditions, as determined by physical examination or medical history that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study;
Significant or uncontrolled psychiatric illness;
Recurrent history or uncontrolled neurological disorders or seizures;
Documented HIV-positive participant;
Body mass index > 40 kg/m^2;
Any clinically significant* hematological parameter and/or biochemical laboratory abnormality.

*The investigator should use his/her clinical judgment to decide which abnormalities are clinically significant.

Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study.

Prior/Concomitant therapy

Use of any investigational or non-registered product other than the study intervention(s) during the period starting 30 days before study intervention (Day -29 to Day 1), or planned use during the study period;
Administration of long-acting immune-modifying drugs at any time during the study period;
Administration of immunoglobulins and/or any blood products or plasma derivatives during the period starting 3 months before the study intervention or planned administration during the study period;
Chronic administration of immunosuppressants or other immune-modifying drugs during the period starting 3 months prior to the first study intervention 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 the vaccination dose;
Administration of a seasonal influenza vaccine during the 6 months preceding entry into the study;
Previous experimental vaccination against RSV.

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

Other exclusions

Pregnant or lactating female;
Female planning to become pregnant or planning to discontinue contraceptive precautions;
Alcoholism or substance use disorder within the past 24 months based on the presence of two or more of the following abuse criteria: hazardous use, social/interpersonal problems related to use, neglected major roles to use, withdrawal tolerance, use of larger amounts or longer, repeated attempts to quit or control use, much time spent using, physical or psychological problems related to use, activities given up to use, craving;
Any study personnel or their immediate dependents, family, or household members.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	West Palm Beach	Florida	United States	33409
2	GSK Investigational Site	Stockbridge	Georgia	United States	30281
3	GSK Investigational Site	Peoria	Illinois	United States	61614
4	GSK Investigational Site	Springfield	Missouri	United States	65802
5	GSK Investigational Site	Seattle	Washington	United States	98105
6	GSK Investigational Site	Surrey	British Columbia	Canada	V3S 2N6
7	GSK Investigational Site	Vancouver	British Columbia	Canada	V6Z 2T1
8	GSK Investigational Site	Truro	Nova Scotia	Canada	B2N 1L2
9	GSK Investigational Site	London	Ontario	Canada	N5W 6A2
10	GSK Investigational Site	Sarnia	Ontario	Canada	N7T 4X3
11	GSK Investigational Site	Toronto	Ontario	Canada	M9W 4L6
12	GSK Investigational Site	Mirabel	Quebec	Canada	J7J 2K8
13	GSK Investigational Site	Pointe-Claire	Quebec	Canada	H9R 4S3
14	GSK Investigational Site	Sherbrooke	Quebec	Canada	J1L 0H8
15	GSK Investigational Site	St-Charles-Borromée	Quebec	Canada	J6E 2B4
16	GSK Investigational Site	Quebec		Canada	G1W 4R4
17	GSK Investigational Site	Espoo		Finland	02230
18	GSK Investigational Site	Helsinki		Finland	00100
19	GSK Investigational Site	Helsinki		Finland	00930
20	GSK Investigational Site	Jarvenpaa		Finland	04400
21	GSK Investigational Site	Kokkola		Finland	67100
22	GSK Investigational Site	Pori		Finland	28100
23	GSK Investigational Site	Seinajoki		Finland	60100
24	GSK Investigational Site	Tampere		Finland	33100
25	GSK Investigational Site	Turku		Finland	20520
26	GSK Investigational Site	Gyeonggi-do		Korea, Republic of	15355
27	GSK Investigational Site	Seoul		Korea, Republic of	07441
28	GSK Investigational Site	Seoul		Korea, Republic of	08308
29	GSK Investigational Site	Alcorcón/Madrid		Spain	28922
30	GSK Investigational Site	Madrid		Spain	28006
31	GSK Investigational Site	Madrid		Spain	28034
32	GSK Investigational Site	Madrid		Spain	28041
33	GSK Investigational Site	Madrid		Spain	28046
34	GSK Investigational Site	Majadahonda (Madrid)		Spain	28222
35	GSK Investigational Site	Santiago de Compostela		Spain	15706
36	GSK Investigational Site	Valencia		Spain	46015