The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04605159




Registration number
NCT04605159
Ethics application status
Date submitted
22/10/2020
Date registered
27/10/2020

Titles & IDs
Public title
A Phase III Double-blind Study to Assess Safety and Efficacy of an RSV Maternal Unadjuvanted Vaccine, in Pregnant Women and Infants Born to Vaccinated Mothers
Scientific title
A Phase III, Randomized, Double-blind, Placebo-controlled Multi-country Study to Demonstrate Efficacy of a Single Dose of Unadjuvanted RSV Maternal Vaccine, Administered IM to Pregnant Women 18 to 49 Years of Age, for Prevention of RSV Associated LRTIs in Their Infants up to 6 Months of Age
Secondary ID [1] 0 0
2020-001355-40
Secondary ID [2] 0 0
212171
Universal Trial Number (UTN)
Trial acronym
GRACE
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
Treatment: Other - RSV MAT
Treatment: Drugs - Placebo

Experimental: RSV_MAT Group - Maternal participants randomized to the RSV_MAT Group will receive a single dose of RSV MAT vaccine at day 1, via the intramuscular route; the preferred injection site will be the deltoid region of the non-dominant arm.

Placebo comparator: Control Group - Maternal participants randomized to the Control Group will receive a single dose of Placebo at day 1, via the intramuscular route; the preferred injection site will be the deltoid region of the non-dominant arm.


Treatment: Other: RSV MAT
One dose of RSV MAT vaccine reconstituted with NaCl solution administered intramuscularly in the non-dominant arm.

Treatment: Drugs: Placebo
One dose of lyophilized sucrose reconstituted with NaCl solution administered intramuscularly in the non-dominant arm.

Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of infant participants with medically assessed, RSV-associated LRTIs, up to 6 months of age
Timepoint [1] 0 0
From birth to Day 181 post birth
Primary outcome [2] 0 0
Number of infant participants with at least one SAE, AE leading to study termination or Medically Attended AE (MAE), from birth up to 6 months after birth
Timepoint [2] 0 0
From birth to Month 6 post birth
Primary outcome [3] 0 0
Number of infant participants with at least one SAE, AE leading to study termination or MAE, from birth up to 12 months after birth
Timepoint [3] 0 0
From birth to Month 12 post birth
Secondary outcome [1] 0 0
Number of infant participants with RSV-associated hospitalizations
Timepoint [1] 0 0
From birth to Day 181 post birth
Secondary outcome [2] 0 0
Number of infant participants with all-cause LRTIs
Timepoint [2] 0 0
From birth to Day 181 post birth
Secondary outcome [3] 0 0
Number of infant participants with all-cause LRTIs with hospitalization
Timepoint [3] 0 0
From birth to Day 181 post birth
Secondary outcome [4] 0 0
Number of infant participants with medically assessed, RSV-associated severe LRTIs, up to 12 months of age
Timepoint [4] 0 0
From birth to Day 366 post birth
Secondary outcome [5] 0 0
Number of infant participants with any medically assessed, RSV-associated LRTIs, up to 12 months of age
Timepoint [5] 0 0
From birth to Day 366 post birth
Secondary outcome [6] 0 0
Number of infant participants with severe medically assessed, RSV-associated LRTIs for RSV subtype A and RSV subtype B separately, up to 6 months of age
Timepoint [6] 0 0
From birth to Day 181 post birth
Secondary outcome [7] 0 0
Number of infant participants with any medically assessed, RSV-associated LRTIs for RSV subtype A and RSV subtype B separately, up to 6 months of age
Timepoint [7] 0 0
From birth to Day 181 post birth
Secondary outcome [8] 0 0
Number of infant participants with medically assessed, RSV-associated LRTIs, up to 4 months of age
Timepoint [8] 0 0
From birth to Day 121 post birth
Secondary outcome [9] 0 0
Number of infant participants with all-cause pneumonia
Timepoint [9] 0 0
From birth to Day 181 post birth
Secondary outcome [10] 0 0
Number of infant participants with RSV-associated hospitalizations
Timepoint [10] 0 0
From birth to Day 366 post birth
Secondary outcome [11] 0 0
Number of maternal participants with RSV-associated Medically Attended RTIs (RSV-MA-RTIs)
Timepoint [11] 0 0
From Day 1 (vaccination) to Day 181 post delivery
Secondary outcome [12] 0 0
Humoral immune response in terms of RSV-A neutralizing antibody Geometric Mean Titers (GMTs) in maternal participants, at specified timepoints
Timepoint [12] 0 0
At Day 1 (pre vaccination), Day 31 and at Delivery
Secondary outcome [13] 0 0
Humoral immune response in terms of RSV-A neutralizing antibody GMTs in infant participants, at specified timepoints.
Timepoint [13] 0 0
At birth, Day 43 post birth, Day 121 post birth and Day 181 post birth
Secondary outcome [14] 0 0
Geometric mean ratio between cord blood and maternal RSV MAT IgG-specific antibody concentrations
Timepoint [14] 0 0
At delivery or birth
Secondary outcome [15] 0 0
Number of maternal participants with solicited adverse events (AEs)
Timepoint [15] 0 0
From Day 1 to Day 7
Secondary outcome [16] 0 0
Number of maternal participants with unsolicited AEs
Timepoint [16] 0 0
From Day 1 to Day 30
Secondary outcome [17] 0 0
Number of maternal participants with at least one serious adverse event (SAE), AE leading to study termination or medically attended respiratory tract illness (MA-RTI)
Timepoint [17] 0 0
From Day 1 (vaccination) to Month 6 post delivery
Secondary outcome [18] 0 0
Number of maternal participants with at least one other medically attended AE
Timepoint [18] 0 0
From Day 1 (vaccination) to Day 43 post delivery
Secondary outcome [19] 0 0
Number of maternal participants with each pregnancy outcome
Timepoint [19] 0 0
From Day 1 to Day 43 post delivery
Secondary outcome [20] 0 0
Number of maternal participants with each pregnancy-related AE of special interest (AESI)
Timepoint [20] 0 0
From Day 1 (vaccination) to Day 43 post delivery
Secondary outcome [21] 0 0
Number of infant participants with each neonatal AESI
Timepoint [21] 0 0
From birth to Day 43 post birth

Eligibility
Key inclusion criteria
Maternal participants

* Participants who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
* Participants who give written or witnessed/thumb printed informed consent after the study has been explained, and before any study specific procedures are performed, as per local regulations regulatory requirements.
* Age 18 to 49 years, inclusive, at the time of study intervention.
* Pre-pregnancy BMI 17.0 to 39.9 kg/m2, inclusive.
* In good general maternal health as established by medical history and clinical examination before entering into the study.
* Singleton pregnancy (including instances where the singleton pregnancy derives from a vanishing twin syndrome).
* At 24^0/7 to 34^0/7 weeks of gestation at the time of study vaccination (Visit 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.
* 1st or 2nd 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.
* No fetal genetic abnormalities (based on genetic testing, if performed).
* No significant congenital malformations, as assessed by fetal anomaly ultrasound scan conducted at or beyond 18 weeks of gestation.
* Willing to provide cord blood.
* Who do not plan to give their child for adoption.
* Who plan to reside in the study area for at least one year after delivery.
* Willing to have the infant followed-up after delivery for a period of 12 months.

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 study specific procedure. OR, if permitted by local regulation, documented verbal consent for infant's participation obtained from the parent(s)/LAR(s) at birth, followed by written consent obtained by (or before) Visit 2-newborn.
Minimum age
18 Years
Maximum age
49 Years
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Maternal participants Medical conditions

* History of allergic disease or reactions likely to be exacerbated by any component of the RSV vaccine
* Hypersensitivity to latex
* Significant complications in the current pregnancy:
* Gestational hypertension unless blood pressure it is controlled and maintained in the normal range (<140mmHg and <90mmHg) through diet and/or antihypertensive medications
* Gestational diabetes not controlled by medication, diet and/or exercise
* Pre-eclampsia
* Eclampsia
* Intrauterine Growth Restriction/Fetal Growth Restriction
* Placenta previa
* Placental abruption, placenta accreta/percreta/increta, chorioamnionitis or any abnormalities that can impair the maternal-fetal circulation
* Polyhydramnios
* Oligohydramnios
* Preterm labour or history of preterm labour in the current pregnancy
* Any intervention to prevent preterm delivery or medical treatment for suspected preterm delivery, including administration of systemic corticosteroids for fetal lung maturation
* Cholestasis
* Other pregnancy-related complications (per investigator's judgement)
* Significant structural abnormalities of the uterus or cervix
* History of 2 or more prior stillbirths or neonatal deaths/history of 2 or more preterm births at =34 weeks gestation/3 or more consecutive spontaneous abortions
* Known HIV infection (as per serological tests performed during the current pregnancy)
* Known or suspected HBV or HCV infection
* Known or suspected infection during the current pregnancy with Toxoplasma, Parvovirus B19, Syphilis, Zika, Rubella, Varicella, CMV or primary genital Herpes Simplex
* Active infection with tuberculosis
* Known or suspected impairment of the immune system
* Current autoimmune disorder for which the participant has received immune-modifying therapy within 6 months before study vaccination, or plans administration through delivery
* Lymphoproliferative disorder or malignancy within 5 years before study vaccination
* Acute or chronic clinically significant abnormality or poorly controlled pre-existent co-morbidities or any other clinical conditions that might pose additional risk to the participant due to participation in the study
* Any conditions that may interfere with participant's ability to comply with study procedures or receipt of prenatal care
* Any condition which would increase the risks of study participation to the unborn infant

Prior/Concomitant therapy

* Prior receipt of an RSV vaccine in the current pregnancy
* Use of any investigational/non-registered product other than the study vaccine/product as described below, or planned use during the period :
* For a drug, vaccine or medical device: from 29 days before the dose of study vaccine
* For immunoglobulins: 3 months before the dose of study vaccine/product.

The exception to this is investigational products administered in the setting of a pandemic which may be allowed following delivery

* Planned administration/administration of any vaccine from 29 days before the dose of study vaccine or planned administration through delivery, except:
* Seasonal influenza vaccines, tetanus vaccines, dTpa/Tdap - alone vaccines, dTpa/Tdap vaccines that also contain other antigens, Hepatitis B vaccines, and COVID-19 vaccines all of which may be administered according to standard of care =15 days before or after study vaccination
* Administration of immunoglobulins (except anti-Rh0D IG, which may be administered at any time), blood products or plasma derivatives within 3 months before study vaccination or planned administration through delivery
* Administration of immune-modifying therapy within 6 months before the study vaccination, or planned administration through delivery. This includes but is not limited to:
* Azathioprine, mycophenolate mofetil, 6-mercaptopurine, cyclosporine, tacrolimus, monoclonal or polyclonal antibodies
* Prednisone =5 mg/day or equivalent for =14 days; Inhaled, intra-articular/intra-bursal and topical steroids are allowed
* Corticosteroids administered for fetal lung maturation

Prior/Concurrent clinical study experience

- Concurrently participating in another clinical study, in which the participant has been or will be exposed to an investigational or a non-investigational vaccine/product

Other exclusions

* Alcoholism or substance use disorder within the past 24 months based on DSM-5 criteria
* A local condition that precludes injection of the study vaccine/product or precludes assessment of local reactogenicity
* Consanguinity of maternal participant and her partner (second degree cousins or closer)
* Any study personnel or their immediate dependants, family or household members

Infant participants

* Concurrently participating in another clinical study, 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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC,WA
Recruitment hospital [1] 0 0
GSK Investigational Site - South Brisbane
Recruitment hospital [2] 0 0
GSK Investigational Site - Southport
Recruitment hospital [3] 0 0
GSK Investigational Site - Geelong
Recruitment hospital [4] 0 0
GSK Investigational Site - Melbourne
Recruitment hospital [5] 0 0
GSK Investigational Site - Nedlands
Recruitment postcode(s) [1] 0 0
4101 - South Brisbane
Recruitment postcode(s) [2] 0 0
4215 - Southport
Recruitment postcode(s) [3] 0 0
3220 - Geelong
Recruitment postcode(s) [4] 0 0
3168 - Melbourne
Recruitment postcode(s) [5] 0 0
6009 - Nedlands
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
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Idaho
Country [6] 0 0
United States of America
State/province [6] 0 0
Louisiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Michigan
Country [8] 0 0
United States of America
State/province [8] 0 0
Montana
Country [9] 0 0
United States of America
State/province [9] 0 0
Nebraska
Country [10] 0 0
United States of America
State/province [10] 0 0
New Mexico
Country [11] 0 0
United States of America
State/province [11] 0 0
New York
Country [12] 0 0
United States of America
State/province [12] 0 0
Ohio
Country [13] 0 0
United States of America
State/province [13] 0 0
South Carolina
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
Argentina
State/province [15] 0 0
Buenos Aires
Country [16] 0 0
Argentina
State/province [16] 0 0
Tucumán
Country [17] 0 0
Argentina
State/province [17] 0 0
Rio Cuarto
Country [18] 0 0
Bangladesh
State/province [18] 0 0
Dhaka
Country [19] 0 0
Bangladesh
State/province [19] 0 0
Sylhet
Country [20] 0 0
Belgium
State/province [20] 0 0
Genk
Country [21] 0 0
Belgium
State/province [21] 0 0
Gent
Country [22] 0 0
Belgium
State/province [22] 0 0
Kortrijk
Country [23] 0 0
Belgium
State/province [23] 0 0
Leuven
Country [24] 0 0
Belgium
State/province [24] 0 0
Sint-Niklaas
Country [25] 0 0
Brazil
State/province [25] 0 0
Rio Grande Do Sul
Country [26] 0 0
Brazil
State/province [26] 0 0
São Paulo
Country [27] 0 0
Brazil
State/province [27] 0 0
Alto Da Posse, Nova Iguacu
Country [28] 0 0
Brazil
State/province [28] 0 0
São José do Rio Preto
Country [29] 0 0
Canada
State/province [29] 0 0
Nova Scotia
Country [30] 0 0
Canada
State/province [30] 0 0
Ontario
Country [31] 0 0
Canada
State/province [31] 0 0
Québec
Country [32] 0 0
Colombia
State/province [32] 0 0
Barranquilla
Country [33] 0 0
Colombia
State/province [33] 0 0
Bogota
Country [34] 0 0
Colombia
State/province [34] 0 0
Cali
Country [35] 0 0
Colombia
State/province [35] 0 0
Chía
Country [36] 0 0
Colombia
State/province [36] 0 0
Medellin
Country [37] 0 0
Dominican Republic
State/province [37] 0 0
Santo Domingo Este
Country [38] 0 0
Finland
State/province [38] 0 0
Helsinki
Country [39] 0 0
Finland
State/province [39] 0 0
Kokkola
Country [40] 0 0
Finland
State/province [40] 0 0
Oulu
Country [41] 0 0
Finland
State/province [41] 0 0
Tampere
Country [42] 0 0
Finland
State/province [42] 0 0
Turku
Country [43] 0 0
France
State/province [43] 0 0
Bordeaux
Country [44] 0 0
France
State/province [44] 0 0
Clermont Ferrand
Country [45] 0 0
France
State/province [45] 0 0
Montpellier cedex 5
Country [46] 0 0
France
State/province [46] 0 0
Paris
Country [47] 0 0
France
State/province [47] 0 0
Pierre Bénite
Country [48] 0 0
Honduras
State/province [48] 0 0
Comayagua
Country [49] 0 0
Honduras
State/province [49] 0 0
San Pedro Sula
Country [50] 0 0
India
State/province [50] 0 0
Kolkata
Country [51] 0 0
India
State/province [51] 0 0
Mangalore
Country [52] 0 0
India
State/province [52] 0 0
Mysuru
Country [53] 0 0
India
State/province [53] 0 0
Nagpur
Country [54] 0 0
India
State/province [54] 0 0
Pune
Country [55] 0 0
Italy
State/province [55] 0 0
Lombardia
Country [56] 0 0
Italy
State/province [56] 0 0
Piemonte
Country [57] 0 0
Italy
State/province [57] 0 0
Puglia
Country [58] 0 0
Italy
State/province [58] 0 0
Sicilia
Country [59] 0 0
Italy
State/province [59] 0 0
Toscana
Country [60] 0 0
Italy
State/province [60] 0 0
Verona
Country [61] 0 0
Korea, Republic of
State/province [61] 0 0
Daegu-si
Country [62] 0 0
Korea, Republic of
State/province [62] 0 0
Seoul
Country [63] 0 0
Mexico
State/province [63] 0 0
Michoacán
Country [64] 0 0
Mexico
State/province [64] 0 0
Nuevo León
Country [65] 0 0
Mexico
State/province [65] 0 0
Querétaro
Country [66] 0 0
Mexico
State/province [66] 0 0
Chihuahua
Country [67] 0 0
Mexico
State/province [67] 0 0
Oaxaca
Country [68] 0 0
Mexico
State/province [68] 0 0
San Luis Potosí
Country [69] 0 0
New Zealand
State/province [69] 0 0
Auckland
Country [70] 0 0
New Zealand
State/province [70] 0 0
Newtown
Country [71] 0 0
Panama
State/province [71] 0 0
Panama City
Country [72] 0 0
Panama
State/province [72] 0 0
Panama
Country [73] 0 0
Philippines
State/province [73] 0 0
Dasmariñas, Cavite
Country [74] 0 0
Philippines
State/province [74] 0 0
Manila
Country [75] 0 0
South Africa
State/province [75] 0 0
Gauteng
Country [76] 0 0
South Africa
State/province [76] 0 0
Johannesburg
Country [77] 0 0
South Africa
State/province [77] 0 0
Soshanguve
Country [78] 0 0
Spain
State/province [78] 0 0
Andalucia
Country [79] 0 0
Spain
State/province [79] 0 0
Galicia
Country [80] 0 0
Spain
State/province [80] 0 0
Madrid
Country [81] 0 0
Spain
State/province [81] 0 0
Aravaca
Country [82] 0 0
Spain
State/province [82] 0 0
Barcelona
Country [83] 0 0
Spain
State/province [83] 0 0
Basurto/Bilbao
Country [84] 0 0
Spain
State/province [84] 0 0
Burgos
Country [85] 0 0
Spain
State/province [85] 0 0
Gandía (Valencia)
Country [86] 0 0
Spain
State/province [86] 0 0
Getafe/Madrid
Country [87] 0 0
Spain
State/province [87] 0 0
Majadahonda (Madrid)
Country [88] 0 0
Spain
State/province [88] 0 0
Malaga
Country [89] 0 0
Spain
State/province [89] 0 0
Marbella
Country [90] 0 0
Spain
State/province [90] 0 0
Sevilla
Country [91] 0 0
Spain
State/province [91] 0 0
Torrejón Ardoz
Country [92] 0 0
Spain
State/province [92] 0 0
Valencia
Country [93] 0 0
Spain
State/province [93] 0 0
Valladolid
Country [94] 0 0
Taiwan
State/province [94] 0 0
Changhua
Country [95] 0 0
Taiwan
State/province [95] 0 0
Kaohsiung City
Country [96] 0 0
Taiwan
State/province [96] 0 0
Taichung
Country [97] 0 0
Taiwan
State/province [97] 0 0
Taipei City
Country [98] 0 0
Taiwan
State/province [98] 0 0
Taipei
Country [99] 0 0
Taiwan
State/province [99] 0 0
Taoyuan
Country [100] 0 0
Thailand
State/province [100] 0 0
Bangkok
Country [101] 0 0
Thailand
State/province [101] 0 0
Muang
Country [102] 0 0
United Kingdom
State/province [102] 0 0
Edinburgh

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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
IPD for this study will be made available via the Clinical Study Data Request site.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
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.
Available to whom?
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.
Available for what types of analyses?
How or where can data be obtained?


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.