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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04980391




Registration number
NCT04980391
Ethics application status
Date submitted
20/07/2021
Date registered
28/07/2021
Date last updated
6/02/2024

Titles & IDs
Public title
A Study on the Safety and Immune Response to an Unadjuvanted RSV Maternal Vaccine, in High Risk Pregnant Women Aged 15 to 49 Years and Infants Born to the Vaccinated Mothers
Scientific title
A Phase III, Double-blind, Randomized, Placebo-controlled Study to Evaluate the Safety, Reactogenicity and Immune Response of a Single Intramuscular Dose of Unadjuvanted RSV Maternal Vaccine, in High Risk Pregnant Women Aged 15 to 49 Years and Infants Born to the Vaccinated Mothers
Secondary ID [1] 0 0
2021-000994-96
Secondary ID [2] 0 0
214725
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Respiratory Syncytial Virus Infections 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - RSV MAT
Treatment: Drugs - Placebo

Experimental: RSV_MAT Group - Maternal participants randomized to the RSV_MAT Group receive a single dose of the RSV MAT vaccine administered intramuscularly between 24 and 36 weeks of gestation (Day 1) and are followed up until 180 days post-delivery.

Placebo Comparator: Control Group - Maternal participants randomized to the Control Group receive a single dose of placebo administered intramuscularly between 24 and 36 weeks of gestation (Day 1) and are followed up until 180 days post-delivery.


Other interventions: RSV MAT
Single dose of the RSV MAT vaccine reconstituted with NaCl solution, administered intramuscularly in the non-dominant arm, at Day 1.

Treatment: Drugs: Placebo
Single dose of placebo, administered intramuscularly in the non-dominant arm, at Day 1.
Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of maternal participants reporting solicited administration site events
Timepoint [1] 0 0
From Day 1 to Day 7 included
Primary outcome [2] 0 0
Percentage of maternal participants reporting solicited systemic events
Timepoint [2] 0 0
From Day 1 to Day 7 included
Primary outcome [3] 0 0
Percentage of maternal participants reporting unsolicited adverse events (AEs)
Timepoint [3] 0 0
From Day 1 to Day 30 included
Primary outcome [4] 0 0
Percentage of maternal participants reporting serious adverse events (SAEs), (S)AEs leading to study withdrawal, and medically attended adverse events (MAEs)
Timepoint [4] 0 0
From Day 1 up to 42 days post-delivery
Primary outcome [5] 0 0
Percentage of maternal participants reporting pregnancy outcomes
Timepoint [5] 0 0
From Day 1 up to 42 days post-delivery
Primary outcome [6] 0 0
Percentage of maternal participants reporting pregnancy-related adverse events of special interest (AESIs)
Timepoint [6] 0 0
From Day 1 up to 42 days post-delivery
Primary outcome [7] 0 0
Percentage of maternal participants reporting worsening of pre-existing medical conditions and/or obstetric complications from Day 1 up to 42 days post-delivery
Timepoint [7] 0 0
From Day 1 up to 42 days post-delivery
Primary outcome [8] 0 0
Percentage of infant participants reporting neonatal / infant AESIs
Timepoint [8] 0 0
From birth up to 42 days post-birth
Primary outcome [9] 0 0
Percentage of infant participants reporting SAEs, (S)AEs leading to study withdrawal, and MAEs
Timepoint [9] 0 0
From birth up to 42 days post-birth
Primary outcome [10] 0 0
Percentage of infant participants reporting SAEs, (S)AEs leading to study withdrawal, and MAEs
Timepoint [10] 0 0
From birth up to 180 days post-birth
Primary outcome [11] 0 0
Percentage of infant participants reporting SAEs, (S)AEs leading to study withdrawal, and MAEs
Timepoint [11] 0 0
From birth up to 365 days post-birth
Primary outcome [12] 0 0
Humoral immune response in terms of RSV MAT immunoglobulin G (IgG)-specific antibody concentrations at pre-dosing (Day 1) for maternal participants
Timepoint [12] 0 0
At Day 1 (pre-dosing)
Primary outcome [13] 0 0
Humoral immune response in terms of RSV MAT IgG-specific antibody concentrations at delivery for maternal participants
Timepoint [13] 0 0
At delivery
Primary outcome [14] 0 0
Humoral immune response in terms of RSV-A neutralizing antibody titers at pre-dosing (Day 1) for maternal participants
Timepoint [14] 0 0
At Day 1 (pre-dosing)
Primary outcome [15] 0 0
Humoral immune response in terms of RSV-A neutralizing antibody titers at delivery for maternal participants
Timepoint [15] 0 0
At delivery
Primary outcome [16] 0 0
Geometric Mean Ratio between cord blood and maternal RSV MAT IgG-specific antibody concentrations.
Timepoint [16] 0 0
At delivery
Primary outcome [17] 0 0
Humoral immune response in terms of RSV MAT IgG-specific antibody concentrations at delivery for infant participants
Timepoint [17] 0 0
At delivery
Primary outcome [18] 0 0
Humoral immune response in terms of RSV-A neutralizing antibody titers at delivery for infant participants
Timepoint [18] 0 0
At delivery
Secondary outcome [1] 0 0
Percentage of maternal participants reporting SAEs, (S)AEs leading to study withdrawal, and MAEs
Timepoint [1] 0 0
From Day 1 up to 180 days post-delivery
Secondary outcome [2] 0 0
Percentage of maternal participants reporting worsening of pre-existing medical conditions and/or obstetric complications from Day 1 post-dosing up to 180 days post-delivery
Timepoint [2] 0 0
From Day 1 post-dosing up to 180 days post-delivery
Secondary outcome [3] 0 0
Percentage of maternal participants reporting RSV-associated medically attended respiratory tract illnesses (MA-RTIs)
Timepoint [3] 0 0
From Day 1 up to 180 days post-delivery
Secondary outcome [4] 0 0
Percentage of infant participants reporting medically assessed, RSV-associated LRTIs
Timepoint [4] 0 0
From birth up to 365 days post-birth
Secondary outcome [5] 0 0
Percentage of infant participants reporting medically assessed, RSV-associated hospitalizations
Timepoint [5] 0 0
From birth up to 365 days post-birth
Secondary outcome [6] 0 0
Humoral immune response in terms of RSV MAT IgG-specific antibody concentrations at Day 31 post-dosing for maternal participants
Timepoint [6] 0 0
At Day 31 post-dosing
Secondary outcome [7] 0 0
Humoral immune response in terms of RSV-A neutralizing antibody titers at Day 31 post-dosing for maternal participants
Timepoint [7] 0 0
At Day 31 post-dosing
Secondary outcome [8] 0 0
Humoral immune response in terms of RSV-B neutralizing antibody titers at pre-dosing (Day 1), Day 31 post-dosing and delivery for maternal participants
Timepoint [8] 0 0
At pre-dosing (Day 1), Day 31 post-dosing and delivery
Secondary outcome [9] 0 0
Humoral immune response in terms of RSV-B neutralizing antibody titers at delivery for infant participants
Timepoint [9] 0 0
At delivery
Secondary outcome [10] 0 0
Humoral immune response in terms of RSV MAT IgG-specific antibody concentrations at Day 43, Day 121 and Day 181 post-birth for infant participants
Timepoint [10] 0 0
At Day 43, Day 121 and Day 181 post-birth
Secondary outcome [11] 0 0
Humoral immune response in terms of RSV-A neutralizing antibody titers at Day 43, Day 121 and Day 181 post-birth for infant participants
Timepoint [11] 0 0
At Day 43, Day 121 and Day 181 post-birth
Secondary outcome [12] 0 0
Humoral immune response in terms of RSV-B neutralizing antibody titers at Day 43, Day 121 and Day 181 post-birth for infant participants
Timepoint [12] 0 0
At Day 43, Day 121 and Day 181 post-birth

Eligibility
Key inclusion criteria
Maternal participants

* Participants who can and will comply with the requirements of the protocol.
* Participants and LARs who give written or witnessed/thumb printed informed consent after the study has been explained according to local regulatory requirements, and before any study specific procedures are performed. The informed consent given at screening should either:

* include consent for both the maternal participant's participation* and participation of the infant after the infant's birth, or
* include consent for the maternal participant's participation* and expressed willingness to consider permitting the infant to take part after the infant's birth (if local regulations/guidelines require parent(s) to provide an additional informed consent after the infant's birth).
* both mother and father should consent if local regulations / guidelines require it.
* Pre-pregnancy Body Mass Index (based on participant's report) 18.5 to 39.9 kg/m^2, inclusive.
* Healthy adolescent pregnant women, 15 to 17 YOA, inclusive, at the time of study intervention administration.

OR

* Pregnant women, 18 to 49 YOA, inclusive, at the time of study intervention administration with:

* HIV infection AND/OR
* Obstetric complications or risk factors during the current pregnancy, where the expectant management of the pregnancy is possible and without evidence of non-reassuring fetal status (only cases for which fetal heart rate can be ascertained) as follows:
* Gestational diabetes, well-controlled on medications (with or without diet or exercise)
* Gestational hypertension, well-controlled on diet or medications below 160/110 mmHg.
* Pre-eclampsia without severe features (i.e. eclampsia, severe hypertension [>160/110 mmHg], organ dysfunction, unstable or complicated by [HELLP] syndrome).
* Fetal Growth Restriction in singleton pregnancies, with normal umbilical artery Doppler and estimated fetal weight 3 to 10th percentile for gestational age.
* History of threatened preterm labor in the current pregnancy, with no cervical dilation greater than 2 cm or effacement exceeding 50%, and/or no progressive change in cervical dilation or effacement detected by serial examinations, when maternal participant is asymptomatic
* Uncomplicated twin gestation.
* Pregnant females at 24^0/7 to 36^0/7 weeks of gestation at the time of study intervention administration (Day 1), as established by:

* Last menstrual period (LMP) date corroborated by first or second trimester ultrasound examination (U/S) (i.e. at or before 28 weeks of gestation).
* First or second trimester U/S only, if LMP is unknown/uncertain.
* Certain LMP, corroborated by an U/S performed after 28 weeks of gestation is also acceptable.

The level of diagnostic certainty of the gestational age should be established by using the Global Alignment of Immunization Safety Assessment in pregnancy (GAIA) gestation age assessment tool

* Participants who are willing to provide cord blood.
* Willing to have their offspring followed-up after delivery for a period of 12 months.
* Participants who do not plan to give their offspring for adoption or place the child in care.

Note that women whose pregnancies resulted from Assisted Reproductive Technologies may be enrolled if they meet all inclusion criteria and none of the exclusion criteria.

Infant participants

* Live-born from the study pregnancy.
* If required per local regulations / guidelines, re-signed (confirmed) written or witnessed/thumb printed informed consent for study participation of the infant obtained from the infant's mother and/or father and/or LAR, before performing any infant study specific procedure. To comply with RTI surveillance and other protocol required procedures that begin immediately after birth: if written consent cannot be provided by the parent(s)/LAR(s) readily post-birth, verbal consent - if permitted per local regulation -- may be sought from the parent(s) / LAR(s) instead. Verbal consent should be documented in the source data by the investigator or delegate. The parent(s) / LAR(s) will provide additional, written informed consent by (or before) Visit 2-NB.
Minimum age
15 Years
Maximum age
49 Years
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Maternal participants Medical conditions

* History of any reaction or hypersensitivity likely to be exacerbated by any component of the study intervention.
* Hypersensitivity to latex.
* Any pre-existing medical conditions or obstetric complications in the current pregnancy that, are poorly controlled and/or with clinical evidence of a non-reassuring fetal status and/or are likely to result in delivery within 7 days after study intervention administration and/or when the timing of planned delivery is within 7 days after study intervention administration and/or acute conditions requiring immediate medical attention for maternal stabilization and/or treatment.
* A multiple pregnancy with 3 or more fetuses.
* Complicated twin gestation.
* Placenta Accreta Spectrum, including placenta increta, percreta, and accreta.
* Fetal structural defects or genetic abnormalities that affect (or are likely to affect) fetal health or survival during the first year of life.
* Known or suspected impairment of the immune system or immunodeficiency syndrome other than HIV.
* Lymphoproliferative disorder or malignancy within 5 years before study dose administration.
* Any illness of the mother or conditions of the fetus that, may substantially interfere with the maternal participant's ability to comply with study procedures, or could increase the risks to the mother or the fetus, or could preclude the evaluation of the participant's data.
* Any other clinical condition that, might pose additional risk to the participant due to participation in the study, as determined by medical history, physical examination or laboratory screening tests.
* Women with any diagnosis, condition, treatment, or other factor that, has the potential to affect or confound assessments of immunogenicity or safety
* Any conditions which, in the investigator's opinion, would increase the risks of study participation to the unborn infant.

Prior/Concomitant therapy

* Prior receipt of an RSV maternal vaccine.
* Use of any investigational or non-registered product other than the study intervention(s) during the period beginning:

* For a drug, vaccine or medical device: 29 days before the dose of study intervention(s) (Day -28 to Day 1), or their planned use during the study period.
* For immunoglobulins: 90 days before the dose of study intervention(s), or their planned use during the study period.

The exception to this is investigational products administered in the setting of a pandemic. Administration in this case should respect the same period outlined above prior to study intervention administration, but may be allowed following delivery.

* Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 29 days before the study Day 1 and ending at delivery, with the exception of seasonal influenza vaccines, tetanus vaccines, dTpa/Tdap - alone vaccines, dTpa/Tdap vaccines that also contain other antigens and Hepatitis B vaccines, all of which may be administered according to standard of care = 15 days before or after study intervention (Day 1).
* Receipt of blood or plasma products or immunoglobulin, from 90 days before study intervention administration, or planned receipt through delivery, with the exception of Rho(D) immunoglobulin, which can be given at any time. In that sense, COVID-19 vaccines may be allowed, when administered = 15 days before or after study vaccination.
* Administration of immune-modifying therapy within 6 months before study intervention administration, or planned administration through delivery, except if it is part of management of HIV infection.

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 intervention.

Other exclusions

* Alcoholism or substance use disorder within the past 24 months based on the presence of 2 or more of the following abuse criteria: hazardous use, social/interpersonal problems related to use, neglect of 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.
* A local condition that precludes injection of the study vaccine/product or precludes assessment of local (administration site) reactogenicity.
* Consanguinity of maternal participant and her partner.
* Any study personnel or their immediate dependents, family, or household members.

Infant participants

* Concurrently participating in another clinical trial, 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.
* Any condition which, would increase the risks of study participation to the infant.
* Child in care.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
3/08/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/05/2023
Sample size
Target
Accrual to date
Final
384
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Louisiana
Country [4] 0 0
United States of America
State/province [4] 0 0
Montana
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
Brazil
State/province [6] 0 0
Rio Grande Do Sul
Country [7] 0 0
Brazil
State/province [7] 0 0
São Paulo
Country [8] 0 0
Canada
State/province [8] 0 0
Nova Scotia
Country [9] 0 0
Canada
State/province [9] 0 0
Ontario
Country [10] 0 0
Canada
State/province [10] 0 0
Québec
Country [11] 0 0
Finland
State/province [11] 0 0
Helsinki
Country [12] 0 0
India
State/province [12] 0 0
Bhubaneshwar, Odisha
Country [13] 0 0
India
State/province [13] 0 0
Mysuru
Country [14] 0 0
Italy
State/province [14] 0 0
Sicilia
Country [15] 0 0
Italy
State/province [15] 0 0
Toscana
Country [16] 0 0
Italy
State/province [16] 0 0
Umbria
Country [17] 0 0
Panama
State/province [17] 0 0
Ciudad de Panama
Country [18] 0 0
Panama
State/province [18] 0 0
Panama
Country [19] 0 0
South Africa
State/province [19] 0 0
Gauteng
Country [20] 0 0
Spain
State/province [20] 0 0
Andalucia
Country [21] 0 0
Spain
State/province [21] 0 0
Boadilla Del Monte (Madrid)
Country [22] 0 0
Spain
State/province [22] 0 0
Madrid
Country [23] 0 0
Spain
State/province [23] 0 0
Majadahonda (Madrid)
Country [24] 0 0
Spain
State/province [24] 0 0
Torrejón Ardoz

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT04980391